Right-sided ligamentum teres (RSLT) is a rare anatomic variant in which the fetal umbilical vein connects to the right portal vein. Patients with RSLT frequently have hepatic vasculature and bile duct anomalies, which increase the risk of complications with hepatectomy. Most patients with RSLT undergo open hepatectomy. We describe a patient with RSLT and hepatocellular carcinoma who underwent laparoscopic hepatectomy. The patient was a 69-year-old man with hepatocellular carcinoma located in the left liver based on computed tomography (CT) and magnetic resonance imaging. Imaging also demonstrated RSLT. Three-dimensional CT analysis revealed independent right lateral type anomalies of the portal vein and bile duct. Laparoscopic extended left lateral sectionectomy was performed after careful surgical planning. Ultrasonography was used frequently during surgery to avoid damaging the right hepatic vasculature. The left lateral and partial left median sections were removed as planned. The patient’s postoperative recovery was uneventful. Avoiding injury to the right hepatic vasculature is essential when performing left lobectomy, including left lateral sectionectomy, in patients with RSLT. Laparoscopic hepatectomy can be performed safely in patients with RSLT, provided that careful surgical planning is conducted using preoperative three-dimensional CT analysis and intraoperative ultrasonography is used.

The aim of this study was to compare the effectiveness of propofol-based sedation and midazo-lam sedation in same-day bidirectional endoscopy (BDE) in children. The charts of children (≤15 years old) who had undergone same-day BDE were retrospectively reviewed. Demographic data, indications, sedatives and their dosages, clinical outcomes, endoscopic findings, adverse events, and patient time requirements were compared in cases with propofol-based and midazolam se-dation. A total of 91 children [51 boys, mean age 13 years (range 9-15)] were enrolled. Propofol alone or in combination with midazolam and/or pentazocine was given in 51 (propofol-based sedation group) while midazolam alone or in combination with pentazocine was given in 40 (midazolam sedation group). The mean doses of propofol, midazolam and pentazocine were 96 mg (range 40–145 mg), 4.1 mg (range 3–5 mg) and 7.5 mg in the propofol group while the mean doses of midazolam and pentazocine were 6.2 mg (range 4–10 mg) and 15 mg in the midazolam group, respectively. The total procedure times and endoscopic findings between the two groups were similar, but the median patient time requirement in the propofol group was significantly shorter than that of the midazolam group (7.3 h vs. 8.4 h, P<0.001). No adverse events occurred in either group. Propofol-based sedation shortened patient time requirements in same-day BDE compared with midazolam sedation in children.

With the introduction of more and more monoclonal antibodies selectively targeting various mediators of the immune-system, together with Janus-Kinase (JAK)-inhibitors with variable affinities towards different JAK subtypes, the available therapeutic options for the treatment of inflammatory bowel diseases (IBD) have undergone an acceleration in the last five years. On the other hand, the prevalence of IBD patients over 65-years of age is steadily increasing and, with this, there is a large population of patients that presents more comorbidities, polypharmacy, and, more frequently, frailty compared to younger patients, exposing them to potentially major risks for adverse events deriving from newer therapies, e.g. infections, cardiovascular risks, and malignancies. Unfortunately, pivotal trials for the commercialization of new therapies rarely include older IBD patients and those with serious comorbidities are virtually excluded. In the present review, we focus on existing literature from pivotal trials and real-world studies, analyzing data on efficacy/effectiveness and safety of newer therapies in older IBD patients with special emphasis on comorbidities and frailty, two distinct but intercorrelated aspects of the older population since age by itself seems to be of minor importance.

Inflammatory processes play major roles in carcinogenesis and progression of hepatocellular carcinoma (HCC) derived from non-alcoholic steatohepatitis (NASH). But there are no therapies for NASH related HCC, especially focusing on these critical steps. Previous studies reported that farnesyltransferase inhibitors (FTIs) have anti-inflammatory and anti-tumor effects. However, the influence of FTIs on NASH-related HCC has not been elucidated. In HCC cell lines, HepG2, Hep3B, and Huh-7, we confirmed expression of hypoxia-inducible factor (HIF)-1α, an accelerator of tumor aggressiveness and the inflammatory response. We established NASH-related HCC models under inflammation and free fatty acid burden and confirmed that HIF-1α expression was increased under both conditions. Tipifarnib, which is an FTI, strongly suppressed increased HIF-1α, inhibited cell proliferation, and induced apoptosis. Simultaneously, intracellular interleukin-6 as an inflammation marker was increased under both conditions and significantly suppressed by tipifarnib. Additionally, tipifarnib suppressed expression of phosphorylated nuclear factor-κB and transforming growth factor-β. Finally, in a NASH-related HCC mouse model burdened with diethylnitrosamine and a high fat diet, tipifarnib significantly reduced tumor nodule formation in association with decreased serum interleukin-6. In conclusion, tipifarnib has anti-tumor and anti-inflammatory effects in a NASH-related HCC model and may be a promising new agent to treat this disease.

Background: Neonatal cholestasis (NC) initiates in the first trimester of a newborn, comprising extra and intrahepatic medical conditions, with a high risk of fatality warranting early diagnosis and treatment to prevent morbimortality. The differential diagnosis of NC is a challenge demanding an accurate diagnosis for disease detection. The current study evaluates NC's clinical symptoms and differential diagnosis using ultrasound, liver biopsy, histopathology, and biochemistry. Methods: Infant registry data from Hevi Pediatric Teaching Hospital (January 2016 - January 2022) were obtained and screened for subject selection. The inclusion criteria include infants with direct hyperbilirubinemia within an onset of 1 to 90 days of birth. As indicated, the recruited subjects underwent liver ultrasound, blood biochemistry, and liver biopsy. Results: Seventy-two children presented with the criteria for inclusion in the study. The study found that ultrasound helped diagnose 43.1% of subjects for BA compared to 34.7% through histopathology. The histopathology confirmed 13 children (18.1%) having neonatal hepatitis. Test sensitivity of the ultrasound method for BA and NH was 60% (40.74, 76.6) and 38.46% (17.71, 64.48), respectively. Conclusion: The study found both ultrasound and liver biopsy to be critical diagnostic methods to differentiate the etiology of NC. Ultrasound has a higher specificity and sensitivity for diagnosing BA than NH. Histopathology and blood biochemistry should be considered, too, for effective diagnosis. In the future, larger sample and multicenter studies should be conducted to develop practically implementable strategies.

According to the World Health Organization, approximately 20 million people worldwide are infected annually with the hepatitis E virus (HEV). There are 4 main genotypes of HEV. Genotype 1 and genotype 2 are common in developing countries and are transmitted by contaminated water from a fecal-oral route. Genotype 3 and genotype 4 are common in developed countries and can lead to occasional transmission to humans by undercooked meat. Hepatitis E virus 1 and HEV3 can lead to fulminant hepatitis, and HEV3 can lead to chronic hepatitis and cirrhosis in immunocompromised patients. The majority of patients with HEV infection are asymptomatic and usually have spontaneous viral clearance without treatment. However, infection in immunocompromised individuals can lead to chronic HEV infection. Both acute and chronic HEV infections can have extrahepatic manifestations. No specific treatment is required for acute HEV infection, no treatment has been approved in chronic infection and no HEV vaccine has been approved by the (United States) Food and Drug Administration. This review focuses on the molecular virology (HEV life cycle, genotypes, model systems, zoonosis), pathogenesis, clinical manifestation, and treatment of chronic HEV infection, especially in immunocompromised patients, to provide clinicians a better understanding of the global distribution of these infections and the significant effect they can have on immunocompromised patients.

Non-alcoholic fatty liver disease (NAFLD) affects about 20–40% of the adult population in high-income countries and is now a leading indication for liver transplantation and can drive to hepatocellular carcinoma. The link between gut microbiota dysbiosis and NAFLD is now clearly established. Through analyses of the gut microbiota with shotgun metagenomics, we observed that compared to healthy controls, Adlercreutzia equolifaciens is depleted in patients with liver diseases such as NAFLD. Its abundance also decreases as the disease progresses and eventually disappears in the last stages indicating a strong association with disease severity. Moreover, we show that A. equolifaciens possesses anti-inflammatory properties, both in vitro and in vivo in a humanized mouse model of NAFLD. Therefore, our results demonstrate a link between NAFLD and the severity of liver disease and the presence of A. equolifaciens and its anti-inflammatory actions. Counterbalancing dysbiosis with this bacterium may be a promising live biotherapeutic strategy of liver diseases..

Anastomotic leakage (AL) after the creation of a gastrointestinal (GI) anastomosis remains an important complication in GI surgery. From its introduction more than 60 years ago, Cyanoacrylate (CA) has gained popularity in colorectal surgery to provide “prophylaxis” against AL. However although in surgical practice it is increasingly used, evidences on humans are still lacking. The aim of this study is to evaluate in humans the safety of CA to seal colorectal anastomosis. All consecutive patients from Jannuary 2022 through December 2022 who underwent minimally invasive colorectal surgery were retrospectively analysed from a prospectively maintained database. Inclusion criteria were histological diagnosis of cancer, totally minimally invasive procedure and absence of intraoperative complications. 103 patients were included in the study, N-butyl cyanoacrylate with metacryloxisulfolane (Glubran 2 ®) was used to seal colorectal anastomosis, no adverse reactions to CA or postoperative complications related to inflammation and adhesions occurred, only one case of AL (0.9%) was recorded. We can consider this study an important proof of concept on safety of CA to seal colorectal anastomosis. It opens the possibility to start performing prospective and comparative studies in humans to evaluate effectiveness of CA in preventing colorectal AL.

The advent of immunotherapy and specifically of immune checkpoint inhibitors (ICIs) for the treatment of solid tumors has deeply transformed therapeutic algorithms in medical oncology. Approximately one third of patients treated with ICIs may develop immune-related adverse events, being the gastrointestinal tract often affected with different grades of mucosal inflammation. Checkpoint inhibitors colitis (CIC) presents with watery or bloody diarrhoea and in case of severe activity requires ICIs discontinuation. The pathogenesis of CIC is multifactorial and still partially unknow: anti-tumor activity that collaterally effects the colonic tissue and the upregulation of specific systemic inflammatory pathways (i.e., CD8+ cytotoxic and CD4+ T lymphocytes) are mainly involved. Many open issues remain on treatment timing and options, and biological treatment, above all with anti-TNF alpha, can be offered to these patients aiming to rapidly resume the oncological therapies. This review aims to summarize the pathogenetic mechanisms underlying CIC and to discuss evidenced-based management including the role of biological therapy.

Evidence of the efficacy and safety of colorectal stent placement for palliation remains insufficient. This single-arm, prospective, multicenter study with WallFlex enteral colonic stent included 200 consecutive patients with malignant large bowl obstruction in the palliation cohort. The technical and clinical success, as well as stent patency and complications as short-term (≤ 7 days) and long-term (&gt; 7days) outcomes, of high axial force self-expandable metal stent (SEMS) placement was evaluated. The technical and clinical success rates were 98.5% and 94.5%, respectively. Non recurrent colorectal obstruction at 1 year was 63.9%, and 71.2% of the patients remained free of recurrent colorectal obstruction until death or the last follow-up. Fifty-six patients (28.0 %) received chemotherapy and five patients were administered bevacizumab after stent placement. The overall complication rate was 47%, including four (2.0%) early-onset and ten (5.0%) late-onset perforations, mostly due to stent-edge injury. Only the use of a long SEMS was a risk factor for perforation. In conclusion, endoscopic colorectal stenting using high axial force SEMS is an effective and safe procedure for palliation in patients with malignant colorectal obstruction. However, care should be taken to avoid perforation at the stent edge when using a long SEMS.

Mucosal healing (MH) is the main treatment target in ulcerative colitis and Crohn’s disease, and it is defined by a combination of complete endoscopic and histologic remission. Indeed, the complete resolution of mucosal inflammation should be confirmed at histology. Neutrophil infiltration represents the unique histological marker in discriminating the active vs quiescent phase of disease, also including crypt injuries (cryptitis and crypt abscesses), erosions and ulcerations. Basal plasmacytosis do not qualify by itself the remission in inflammatory bowel diseases (IBD), but it represents a diagnostic clue, mostly at onset. Several histological scoring systems have been developed to evaluate therapeutic efficacy, even though they often resulted tricky and subjective. Moreover, these scores listed a heterogeneous group of histological features as parameters. The recently proposed simplified histological score on MH was based on neutrophils and their distribution in the gut mucosa was also considered, aiming to provide a simple, time-sparing and reproducible tool to be applied to the routinary diagnostic practice. The artificial intelligence could be a promising tool both in evaluating and standardizing the histological assessment of disease activity in IBD. Moreover, novel molecules involved in the inflammatory dynamics in the gut could be employed in supporting the diagnostic practice in IBD.

Background & aims. The fourth dose of anti-SARS-CoV-2 vaccine slightly improved the humoral response among previously seronegative liver transplant (LT) recipients. Mycophenolate (MMF) treatment worsens the vaccination response. This study aimed to evaluate whether temporary MMF interruption might improve immunogenicity of the fourth anti-SARS-CoV-2 BNT16b2 vaccine dose in nonresponsive LT recipients. Methods. LT recipients negative for anti-spike glycoprotein-specific immunoglobulin G receptor-binding domain (s-RBD) antibodies after the third vaccine dose were enrolled. Anti-SARS-CoV-2 spike-specific T cell responses were measured before and two months following the fourth vaccine dose, and anti-SARS-CoV-2-s-RBD antibodies also 6 months thereafter. MMF was suspended two weeks before and after vaccination. Results. Five LT recipients were enrolled. After a mean of 78 days after vaccination, all patients tested positive for anti-SARS-CoV-2-s-RBD antibodies. The mean antibody titer was 8944 UI/ml. The positive antibody response was maintained during a mean of 193 days of follow-up. Three patients developed a positive T cell response. Two patients (one positive for T cell response) developed a self-limited SARS-CoV-2 infection. Conclusions. Suspending MMF prior to the fourth dose of anti-SARS-CoV-2 mRNA vaccine seems feasible and safe. This procedure could restore vaccine-induced immunogenicity in a large portion of previously nonresponsive LT recipients.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent condition among postmenopausal women that can lead to severe liver dysfunction and increased mortality. In recent years, research has focused on identifying potential lifestyle dietary interventions that may prevent or treat NAFLD in this population. Due to the complex and multifactorial nature of NAFLD in postmenopausal women, the disease can present as different subtypes, with varying levels of clinical presentation, and variable treatment responses. By recognizing the significant heterogeneity of NAFLD in postmenopausal women, it may be possible to identify specific subsets of individuals who may benefit from targeted nutritional interventions. In this review, we sought to examine the current evidence supporting the role of three specific nutritional factors - choline, soy isoflavones, and probiotics – as potential nutritional adjuvants in the prevention and treatment of NAFLD in postmenopausal women. There is promising evidence supporting the potential benefits of these nutritional factors for NAFLD prevention and treatment, particularly in postmenopausal women, and further research is warranted to confirm their effectiveness in alleviating hepatic steatosis in this population.

The indications for TACE in the treatment of hepatocellular carcinoma have become more stringent with the development of systemic pharmacotherapy. Radical TACE is expected to be used only in situations such as for tumors with small volume which fulfill the “up-to-7”. Furthermore, a combination of molecular-targeted agents is expected to maximize the efficacy of TACE. In the intermediate stage, TACE and drug therapy play complementary roles, and it is important to select a treatment strategy that considers tumor status and hepatic reserve. However, no studies have investigated the various types of TACE in the treatment of such patients. Currently, TACE in Japan is broadly classified into conventional TACE, balloon occluded TACE (B-TACE), and drug-eluting beads TACE (DEB-TACE). This article outlines the evolution of B-TACE for hepatocellular carcinoma in the drug therapy era.

For centuries, Foeniculi fructus (F. fructus) has been used as a traditional herbal medicine in China and Europe and is widely used as a natural therapy for digestive disorders, including indigestion, flatulence, and bloating. The mechanism by which F. fructus alleviates functional dyspepsia was analyzed through network pharmacology, and its therapeutic effect on an animal model of functional dyspepsia was investigated. The compounds, targets, and related diseases of F. fructus were studied utilizing the traditional Chinese medicine systems pharmacology (TCMSP) database. Information on the target genes was classified using the UniProt database. A network was built using Cytoscape 3.9.1, and functional dyspepsia-related genes were checked using the Cytoscape string application. The efficacy of F. fructus on functional dyspepsia, including gastroparesis and gastrointestinal motility, was confirmed by treatment with its extract in a mouse model of loperamide-induced functional dyspepsia. Seven compounds targeted twelve functional dyspepsia-associated genes. In a functional dyspepsia mouse model, F. fructus significantly suppressed the symptoms when compared to that in the control group. Our animal studies showed that the mechanism of action of F. fructus is closely related to gastrointestinal motility. Based on animal experimental results, the results showed that F. fructus provides a potential means to treat functional dyspepsia, suggesting that its medical mechanism for functional dyspepsia can be described by the relationship between seven key compounds of F. fructus, including oleic acid and β-sitosterol, and 12 functional dyspepsia-related genes.

Multifocal hepatic hemangiomas (MHHs) are the most common benign vascular tumours of the liver that are detected in children with concomitant multiple infantile hemangiomas. They still pose a diagnostic problem for GPs and are thus often detected far too late, due to their low prevalence rates. MHHs are usually undetectable at birth, usually detected within the first few weeks of life when the lesions proliferate. The heterogeneity of the lesions and the presence of comorbidities make often the management of infantile hepatic hemangiomas a true challenge, also for highly specialised medical professionals. Ultrasound (USG) should be the imaging examination performed in the first instance in search for vascular anomalies in children. In pharmacotherapy, the first choice treatment is propranolol and prednisone, administered orally. Invasive treatment is usually indicated in symptomatic or progressive multiple hepatic hemangiomas only. Recently published studies show a significant decrease in the incidence rate of the disease, which now ranges between 11% and 18% for treated and untreated hepatic hemangiomas, respectively.

We aimed to evaluate the magnesium content in human cirrhotic liver and its correlation with serum AST levels, expression of hepatocellular injury, and MELDNa prognostic score. In liver biopsies obtained at liver transplantation we measured the magnesium content in liver tissue in 27 cirrhotic patients (CIRs) and 16 deceased donors with healthy liver (CTRLs) by atomic absorption spectrometry and within hepatocytes in 15 CIRs using synchrotron-based X-ray Fluorescence Microscopy. In 31 CIRs and 10 CTRLs we evaluated the immunohistochemical expression in hepatocytes of the transient receptor potential melastatin 7 (TRPM7), a magnesium influx chanzyme also involved in inflammation. CIRs showed a lower hepatic magnesium content [117.2 (IQR 110.5-132.9) vs 162.8 (IQR 155.9-169.8) μg/g; p&lt;0.001] and a higher percentage of TRPM7 positive hepatocytes [53.0 (IQR 36.8-62.0) vs 20.7 (10.7-32.8) %; p&lt;0.001) than CTRLs. In CIRs, MELDNa and serum AST at transplant correlated: a) inversely with the magnesium content both in liver tissue and hepatocytes; b) directly with the percentage of hepatocytes stained intensely for TRPM7. The latter also directly correlated with worsening of MELDNa at transplant compared to waitlisting. Magnesium depletion and overexpression of its influx chanzyme TRPM7 in hepatocytes are associated with severity of hepatocyte injury and prognosis in cirrhosis. These data represent the pathophysiological basis for a possible beneficial effect of magnesium supplementation in cirrhotic patients.

Non-alcoholic steatohepatitis (NASH), which is the most severe manifestation of non-alcoholic fatty liver disease (NAFLD), has been recognized as a major hepatocellular carcinoma (HCC) catalyst. However, the molecular mechanism of NAFLD-NASH-HCC sequence remains unclear and a specific and effective treatment for NASH has not yet been established. The progress in this field depends on the availability of reliable preclinical models which show the steady progress to NASH, liver cirrhosis, and HCC. However, most of NASH mouse models that have been described to date develop NASH generally for more than 24 weeks and there is an uncertainty of HCC development. To overcome such shortcomings of experimental NASH studies, we established a novel NASH-HCC mouse model with very high reproducibility, generality, and convenience. We treated male C57BL/6J mice with a newly developed choline-deficient and methionine-restricted high-fat diet (CDMRHFD) for 60 weeks. Treatment of CDMRHFD for 3 weeks revealed marked steatosis, lobular inflammation, and fibrosis, histologically diagnosed as NASH. Liver cirrhosis was observed in all mice with 36-week treatment. Liver nodule emerged at 12 weeks of the treatment, and diameter >2 mm liver tumors developed in all mice at 24 weeks of the treatment. In conclusion, our rapidly progressive and highly reproducible NASH-liver cirrhosis-HCC model is helpful for preclinical development and research on the pathogenesis of human NAFLD-NASH-HCC. Our mouse model would be useful for the development of novel chemistry for NASH-HCC-targeted therapies or HCC prevention strategies.

Background: Endoscopic Ultrasound (EUS) is widely used for the diagnosis of bilio-pancreatic and gastrointestinal (GI) tract diseases, for the evaluation of subepithelial lesions, and for sampling of lymph nodes and solid masses lo-cated next to the GI tract. The role of Artificial Intelligence in healthcare in growing. This review aimed to provide an overview of the current state of AI in EUS from imaging to pathological diagnosis and training. Methods: AI algorithms can assist in lesion detection and characterization in EUS by analysing EUS images and identifying suspicious areas that may require further clinical evaluation or biopsy sampling. Deep learning tech-niques, such as convolutional neural networks (CNNs), have shown great potential for tumour identification and subepithelial lesion (SEL) evaluation by extracting important features from EUS images and using them to classify or segment the images. Results: AI models with new features can increase the accuracy of diagnoses, provide faster diagnoses, identify subtle differences in disease presentation that may be missed by human eyes, and provide more information and in-sights into disease pathology. Conclusions: The integration of AI in EUS images and biopsies has the potential to improve the diagnostic accura-cy, leading to better patient outcomes and to a reduction of repeated procedures in case of non-diagnostic biopsies.

Kidney fibrosis is a complex polyetiological progressive disease manifesting as an intraorgan proliferation of the connective tissue with the appearance of cicatricial changes. However, pathogenetic mechanisms of renal fibrosis remain poorly understood. The paper highlights features of the protease phenotype and histotopography of mast cells (MCs) found in the kidney, as the key players in extracellular matrix remodeling in nephrofibrosis, detected in a patient diagnosed with "nephrosclerosis with the non-functioning upper pole of the duplex right kidney in the junction of refluxing megaureter of the upper pole of the duplex right kidney". The highest content of MCs was found in the kidney areas with fibrotic changes. MCs were actively involved in the development of inflammatory and fibrotic changes in limited loci of the specific tissue microenvironment of the kidney through targeted secretion of tryptase, chymase, and carboxypeptidase A3 to the vascular endothelium, nephron epithelium, interstitium cells, and components of the intercellular substance. The formation of a profibrotic environment in the kidney interstitium was facilitated by epigenetic effects of tryptase promoting epithelial-mesenchymal transition (EMT) of the nephron epithelium. A selectively increased number and targeted secretory activity of MCs in limited loci of the kidney parenchyma without visible pathological changes evidence a trigger pathogenetic role of specific proteases in the formation of a local microenvironment with a profibrogenic metabolic profile. Thus, MCs are actively involved in the mechanisms of formation and evolution of fibrogenic niches in the kidney; this fact can be used to develop new strategies for therapeutic options of tubulointerstitial fibrosis resulted from chronic kidney injury. Further study of the molecular phenotype of mast cells reveals new fundamental mechanisms of fibrosis pathogenesis being a significant tool for personalized therapy in nephrology.

Background: This literature review investigates qualitative and quantitative uses of indocyanine green (ICG) in surgical treatment, as this novel technique has become increasingly popular in ORs (operating rooms) worldwide due to its many advantages. Method: An extensive literature review was performed by searching for relevant terms in 5 international databases (www.pubmed.gov, www.sciencedirect.com, www.scopus.com, www.Oxfordjournals.com, www.reaxys.com). The results of this search were summarized into the main advantages of employing ICG in colorectal surgery as follows: a) intraoperative fluorescence angiography capability; b) fluorescence-guided identification of lymph node involvement in colorectal cancer and the sentinel lymph node method; c) positive fluorescence flagging of a liver tumour as small as "only" 200 tumour cells; d) facilitation of fistula diagnosis; and e) tumour tattooing. Moreover, in addition to qualitative intraoperative ICG use, this technique can be combined with quantitative methods and parameters, such as maximum intensity, relative maximum intensity, and different inflow parameters (time-to-peak, slope, and t1/2max). The conclusion of this article is that fluorescence surgery with ICG aided by near-infrared (NIR) light is a relatively recent technology, an advantage of which is improving the specific anatomic and functional information provided, thus allowing more comprehensive and safer tumour removal as well as preservation of important structures.

Objectives: We aimed to clarify the endoscopic and clinicopathological features of raspberry-shaped gastric lesions (RSGLs) and to establish an endoscopic diagnostic algorithm for RSGLs. Methods: We collected RSGLs from an endoscopic database at our hospital between May 2009 and August 2021. All RSGLs were histopathologically classified and compared based on their endoscopic and clinicopathological characteristics. Results: Sixty-five RSGLs in 54 patients were classified into five histopathological types: gastric adenocarcinoma of foveolar type (GA-FV, n = 43), gastric adenocarcinoma of fundic-gland type (GA-FG, n = 2), gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM, n = 4), hyperplastic polyp (HP, n = 12), and proton pump inhibitor-related lesion (PPI-L, n = 4). All RSGLs exhibited polygonal or curved marginal crypt epithelium (MCE). GA-FV lesions had homogenously reddish (95%) and irregular microvascular (MV) pattern (91%). GA-FG lesions were heterogeneously reddish with a submucosal tumor shape (100%) and had a regular MV pattern (50%). GA-FGM lesions were homogenously reddish (75%) and occasionally had a submucosal tumor shape (50%) with an irregular MV pattern (75%). HP and PPI-L were homogeneously reddish (93%), with linear or dotted MCE (81%) and a regular MV pattern (100%). Conclusion: Our diagnostic algorithm for RSGLs constructed using endoscopic features might be useful for the endoscopic differential diagnosis of RSGLs.

Drug induced liver injury (DILI) is the most common cause of acute liver failure and 5-10% of patients hospitalized for jaundice are diagnosed with DILI. For a diagnosis of DILI to be made, there should be exclusion of other etiologies of liver injury and the use of a precipitator drug, latency of symptoms, and resolution of liver injury once the offending drug is identified and discontinued. In our case report, we present a patient with idiosyncratic hepatocellular pattern DILI after two doses of ocrelizumab for treatment of multiple sclerosis. Ocrelizumab was given 16 and 27 days prior to the onset of icterus, jaundice, and fatigue, in a patient without the evidence of prior exposure to hepatitis B virus. At presentation labs revealed severe acute hepatocellular liver injury with R factor of 30.42, marked hyperbilirubinemia, and transient hypoalbuminemia. No evidence of latent or active hepatitis B infection was detected. Drug dechallenge led to return of liver chemistries to near-normal levels 31 days after the onset of her symptoms. This case indicates DILI diagnosis associated with the use of ocrelizumab, and warrants careful monitoring of liver functions in patients even in the absence of hepatitis B.

Acute pancreatitis (AP) is the most common gastrointestinal disease leading to hospitalizations. The development of AP leads to damage of the pancreatic microcirculation with a cascade of subsequent events resulting, among others, in coagulopathy. Previous research showed that anticoagulants can be an important therapeutic agent. Heparin and acenocoumarol can alleviate the course of AP, as well as accelerate healing and post-inflammatory regeneration of the pancreas. The aim of this study was to check whether warfarin, a drug with more stable effects than acenocoumarol, affects the healing and regeneration of the pancreas in the cerulein-induced AP. AP was evoked in Wistar male rats by intraperitoneal administration of cerulein. The first dose of warfarin (45, 90 or 180 µg/kg/dose) was administered 24 hours after the first dose of cerulein and the doses of warfarin were repeated once a day in subsequent 10 days. The severity of acute pancreatitis was assessed immediately after the last dose of cerulein, as well as 1, 2, 3, 5, and 10 days after AP induction. Treatment with warfarin dose-dependently increased interna-tional normalized ratio (INR) and attenuated the severity of pancreatitis in histological ex-amination and accelerated pancreatic recovery. Those effects were accompanied with a faster reduction in the pancreatitis-evoked increase in serum activity of amylase and lipase, serum concentration of pro-inflammatory interleukin-1β, and plasma level of D-Dimer. In addition, treatment with warfarin decreased pancreatic weight and improved pancreatic blood flow in rats with AP. The therapeutic effect was particularly pronounced after the administration of warfarin at a dose of 90 µg/kg/dose. Conclusion: Administration of warfarin accelerates re-generation of the pancreas and recovery in the course of cerulein-induced mild-edematous acute pancreatitis.

Abstract Objective：To explore the efficacy of modified Altemeier procedure in the treatment of complete rectal prolapse. Method and Main outcome measures:The enrolled patients with complete rectal prolapse were divided into traditional and modified groups according to the surgical approach.The primary outcomes included complication rates, time and severity of postoperative recurrence, changes in pre- and postoperative Wexner anal incontinence scores and ED-5Q-5L quality-of-life autonomy scores. Secondary outcomes included operative time, intraoperative bleeding, and length of hospital stay. Results:The overall complication rates were 33.33% and 6.67% and recurrence rates were 26.67% and 7% in the traditional and modified groups, respectively (P<0.05)；The duration of surgery in the traditional group was shorter than that in the modified group, but the intraoperative bleeding was significantly higher than that in the modified group, and all differences were statistically significant (P<0.05)；The length of stay and in the two groups, respectively, with no statistically significant difference (P>0.05)；The postoperative Wexner incontinence score and ED-5Q-5L quality of life in the modified group were found to be significantly better than those in the traditional group at 8 months postoperative follow-up, with statistically significant differences (P<0.05). Conclusions:Pathological dilatation of the distal rectum may be another anatomical defect in complete rectal prolapse. The results of the clinical study confirmed the clinical effectiveness and safety of the modified Altmeyer procedure, which has high clinical application value.

Intestinal commensal microbes, called the gut microbiota, play a critical role in host immune homeostasis through active microbial metabolites and innate and adaptive immune responses. Dysbiosis or imbalance of the gut microbiota composition is associated with inflammatory bowel disease (IBD) which includes Crohn’s disease and ulcerative colitis. The incidence and prevalence rates of IBD have been increasing worldwide. It is well recognized that butyrate, a microbial metabolite of diet fibers, is a major energy source for colonocytes and plays a crucial role in regulating immune function and maintaining epithelial barrier function and intestinal homeostasis. Emerging evidence suggests that butyrate might be a potential therapeutic agent to treat IBD. In this review, we discuss about gut microbial metabolites, particularly butyrate, the synthesis and metabolism of butyrate, mechanisms of butyrate in immune and epithelial barrier function. Furthermore, we review the current research on various therapeutic implications of butyrate in IBD.

Cholestasis is a condition defined as an abnormal decrease of bile flow due to progressive pathological states or cholestatic liver diseases that affect the biliary tree at intrahepatic and extrahepatic level. It induces complications such as cirrhosis, liver failure, malignancies, pruritus, fatigue, bone disease and nutritional deficiencies that merit close follow-up and specific interventions to improve quality of life. Furthermore, cholestasis can progress to end-stage liver disease and represents an entity with high morbidity and mortality; and economic burden, Therefore, it is important that clinicians understand the treatment options for cholestatic liver diseases. This review addresses the pathophysiology of cholangiopathies, a general view of current treatments and their molecular targets, and a specific review of those groups of drugs. The objective is to provide clinicians with an overview of the current treatment of cholangiopathies based on evidence on its efficacy and safety.

In recent years, nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) has become a leading worldwide disease, and its therapies are facing many complexities. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that belong to the nuclear receptor (NR) superfamily and have three subtypes: PPARα (NR1C1), PPARβ/δ (NR1C2), and PPARγ (NR1C3). They have been identified to be essential in the regulation of lipid metabolism by controlling the transcription of genes related to fatty acids, bile acids, and cholesterol metabolism. Many PPAR agonists have been reported, such as natural agonists (fatty acids, eicosanoids, and phospholipids) and synthetic ligands (fibrates, thiazolidinediones, glitazars, and elafibranor). PPAR-based chemicals have a breakthrough in the innovation of therapy for fatty liver disease. This review will provide an overview of how PPARα and PPARγ play roles in lipid homeostasis, discussing the consideration of their agonists as potential therapeutic agents for NAFLD/NASH.

Background: Corrosive injuries (CI) became medical problems related complications include esophageal, pyloric stricture, squamous cell carcinoma [1], physical and quality of life [2]. Endoscopic dilatation (ED) is primary therapy [3]. The ultrathin endoscope assisted method is potentially safe and useful in avoiding technical failure [4]. Methods: Retrospective study of esophageal and/or pyloric stricture after CI who underwent di-latation at Soetomo General Hospital (July 2018 – July 2022). One-biweekly ED using Ultrathin Endoscope Assisted Method then continued by Through The Scope (TTS) balloon or Bougie dila-tor. Target diameter is 14mm. Clinical outcome included successful, refractory, recurrent rate and complications related procedures Results: Fifteen patients with stricture related CI. Eleven patients underwent ED with total 73 procedures. Mean age 31,45 years, Male 6(54,6%), suicide attempt 7(63,6%), acid agent 9(81,8%) located at esophagus 3(27,3%), pylorus 3(27,3 %), or both 5(45,4%). Number of esophageal dilata-tion to achieve target 14mm was 1-2 and 2-15 procedures for simple and complex stricture with overall successful, recurrent and refractory rate were 75%, 12.5% and 12.5% respectively. Pyloric dilatation outcome were 62.5%, 25% and 12.5% for successful, recurrent and refractory rate re-spectively. Conclusions: Stricture-related corrosive injury has predominantly complex anatomical structure, more sessions are required and lower clinical outcome

Aim: To investigate how much aerobic and resisted physical exercise affects the behavior of AST and ALT proteins in the NAFLD spectrum. Background: Non-alcoholic fatty liver disease (NAFLD) is a pathology resulting from the excessive accumulation of triglycerides in the liver. The pathophysiology of the disease comes from several mechanisms, among them, metabolic, environmental, and genetic. The measurement of liver enzymes, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) are essential to perform a differential diagnosis of NAFLD with other pathologies that affect the liver. The non-pharmacological treatment of NAFLD is based on aerobic and resisted physical exercise, and one of its aims is to reduce the inflammatory markers AST and ALT. Materials and Methods: Systematic review carried out in PubMed, Scopus, Embase, and Cochrane databases. Clinical trials that evaluated the effect of physical exercise on NAFLD on AST and ALT enzymes were included. Results: A total of 24 clinical trials met the inclusion criteria, with a sample size of 1141 participants, aged 20-82 years. The study protocol varied between aerobic exercise and resistance exercise with a weekly frequency between 2-6 times a week, a duration of 20-90 minutes for aerobics, and an intensity between 50-80% of peak VO2 and/or maximum HR for the resisted. Of the 24 studies included, only five showed improvements in both enzymes in the intervention group. Conclusion: Physical exercise cannot make significant changes in the behavior of AST and ALT liver parameters.

Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is an alternative to surgery for acute cholecystitis (AC) in poor operative candidates. However, the role of EUS-GBD in non-cholecystitis (NC) indications has not been well studied. We compared clinical outcomes of EUS-GBD for AC and NC indications. Consecutive patients undergoing EUS-GBD for all indications at a single center were retrospectively analyzed. Fifty-one patients underwent EUS-GBD during the study period. Thirty-nine (76%) patients had AC while 12 (24%) had NC indications. NC indications included malignant biliary obstruction (n = 8), symptomatic cholelithiasis (n = 1), gallstone pancreatitis (n = 1), choledocholithiasis (n = 1), and Mirizzi’s syndrome (n = 1). Technical success was noted in 92% (36/39) for AC and 92% (11/12) for NC (p &gt; 0.99). Clinical success rate was 94% and 100%, respectively (p &gt; 0.99). There were 4 adverse events in the AC group and 3 in the NC group (p = 0.62). Procedure duration (median 43 vs 45 minutes, p = 0.37), post-procedure length of stay (median 3 vs 3 days, p = 0.97), and total gallbladder related procedures (median 2 vs 2, p = 0.59) were similar. EUS-GBD for NC indications is similarly safe and effective as EUS-GBD in AC.

Background and Objectives: A novel synthetic self-assembling peptide, PuraStat, has been introduced as a hemostatic agent. This case series aimed to evaluate the clinical efficacy of PuraStat for gastrointestinal bleeding during emergency endoscopy. Cases: Twenty-five patients with gastrointestinal bleeding who had undergone emergency endoscopy with PuraStat between August 2021 and December 2022 were retrospectively examined. Six patients were receiving antithrombotic agent, and ten patients with refractory gastrointestinal bleeding had undergone at least one endoscopic hemostatic procedure. The breakdown of bleeding was gastroduodenal ulcer/erosion in 12 cases, bleeding after gastroduodenal or colorectal endoscopic resection in 4 cases, rectal ulcer in 2 cases, postoperative anastomotic ulcer in 2 cases, and gastric cancer, diffuse antral vascular ectasia, small intestinal ulcer, colonic diverticular bleeding, and radiation proctitis in each case. The method of hemostasis was only PuraStat application in six cases, and hemostasis in combination with high-frequency hemostatic forceps, hemostatic clip, argon plasma coagulation, and hemostatic agents (i.e. thrombin) in the remaining cases. Rebleeding was observed in three cases. Hemostatic efficiency was observed in 23 cases (92%). Conclusions: PuraStat has the expected hemostatic effect on gastrointestinal bleeding during emergency endoscopy. The use of PuraStat should be considered in emergency endoscopic hemostasis of gastrointestinal bleeding.

Hepatocellular carcinoma is the most common primary malignant hepatic tumor and occurs most often in the setting of chronic liver disease. Liver transplantation is a curative treatment option and is an ideal solution because it solves the chronic underlying liver disorder while removing the malignant lesion. Because of organ shortages this treatment can only be applied to carefully selected patients according to clinical guidelines to minimize risk of recurrence. Artificial intelligence is an emerging technology with multiple applications in medicine with a predilection for domains that work with medical imaging like radiology. With the help of these technologies laborious tasks like segmentation can be automated and workflow in radiology departments can be improved. Other roles include in depth pixel-wise analysis of lesions by radiomics or deep learning in order to find new imaging criteria that allow better prediction of treatment response or risk of recurrence. Liver transplant is an ideal treatment for patients with hepatocellular carcinoma in the setting of chronic liver disease and artificial intelligence could provide solutions for improving the management of liver transplant candidates to improve survival.

Introduction: Levosimendan is a positive inotropic molecule that does not reduce splanchnic circulation and has anti ischemic properties by opening mito KATP channels. Cirrhosis is a chronic and diffuse process characterized by fibrosis and the conversion of typical liver architecture into structurally abnormal nodules. In the late stages of the disease, cirrhosis is responsible for organ failure and complications such as cirrhotic cardiomyopathy and hepatic encephalopathy. Material and methods: We examined the effect of levosimendan in rat models of liver cirrhosis. Male Wistar rats were divided into four groups: Group A: cirrhotic rats 14 days after bile duct ligation (BDL); Group B: control (intact rats); Group A1: BDL and levosimendan (liver cirrhosis induced by bile duct ligation plus intraperitoneal administration of levosimendan); Group B1: control and levosimendan (intact animals with normal liver function treated with an intraperitoneal injection of levosimendan). Each group was subjected to blood sampling to determine GOT, GPT, and bilirubin at baseline, two weeks after surgery, and four days after treatment. In addition, echocardiography was performed in all the groups simultaneously. At the end of the experiments, the rats were subjected to cerebral and hepatic microdialysis and sacrificed. Results: Serum GOT, GPT, and bilirubin in Group A1 (GOT 304 UI/L, GPT 60 UI/L, BIL 3,9 mg/dl) were considerably lower than in Group A (GOT 320 UI/L, GPT 67,16 UI/L, BIL 6,4 mg/dl). The Ejection fraction value decreased significantly postoperatively in Group A (preop 55,66%, BDL 38,85%) and was highest after treatment with levosimendan (Group A1 48,38%). Significant histological differences were detected between the experimental groups (Group A Sheuer staging 3, severe fibrosis, Group A1 Sheuer staging 0-2 no, mild and moderate fibrosis). Group A had a higher value of Lactate, Pyruvate, Glycerol, and Glutamate cerebral microdialysate concentrations (Lac 0.37mM, Pyr 16.25 mcM, Glyc 15.72 mcM, Glut 15.8 mcM) in comparison with BDL rats treated with levosimendan (Group A1 - Lac 0.31 mM, Pyr 6.3 mcM, Glyc 13.66 mcM, Glut 11.15 mcM). Glucose concentrations in cerebral dialysate from Group A were significantly lower (0.13 mM) than in Group A1 (0.25 mM). Glucose and Glycerol concentrations in liver microdialysate from Group A were significantly lower (Gluc 0.95 mM, Glyc 1 mcM) than in Group A1 (Gluc 1.6 mM, Glyc 3.4 mcM). Conversely, in liver dialysate from Group A (0.52 mM), lactate was significantly higher than in Group A1 (0.35 mM). Conclusions: Our results suggest that levosimendan can be potentially protective for fibrotic liver and probably can prevent cirrhosis complication as cirrhotic cardiomyopathy and hepatic encephalopathy.

Abstract: Background and objectives: Symptomatic walled-off pancreatic necrosis is a serious local complication of acute necrotising pancreatitis. The endoscopic step-up approach is the standard treatment for symptomatic walled-off pancreatic necrosis; however, adjunctive radiologic percu-taneous drainage for this condition is controversial. This study compared the clinical and radio-logic resolution of walled-off pancreatic necrosis achieved with the endoscopic step-up approach with or without radiology-guided percutaneous drainage. Material and Methods: This retrospective, single-center cohort study enrolled patients with symp-tomatic walled-off pancreatic necrosis who underwent endoscopic transmural drainage (ETD) followed by directed endoscopic necrosectomy (DEN) with or without radiology-guided drainage. A total of 34 patients (endoscopic approach, n=22; combined modality approach, n=12) underwent the endoscopic step-up approach (ETD followed by DEN). Baseline characteristics, clinical success, and resolution of necrosis were compared between groups. Results: All patients achieved symptom resolution from walled-off pancreatic necrosis. The mean patient age was 58.4 years, and 21 (61.8%) were men. After treatment with the endoscopic approach and combined modality approach, clinical success was achieved in 90.9% of patients within 11.5 days, and 66.7% of patients within 16.5 days, respectively. Both the total hospital stay (55 days vs 71 days; p=0.071) and time to complete radiologic resolution were shorter (93 days vs 124 days; p=0.23) in the endoscopic approach group. Conclusion: The endoscopic step-up approach resulted in the clinical resolution of symptomatic walled-off pancreatic necrosis comparable to that of the combined modality drainage. However, the endoscopic approach alone allows higher clinical success, early clinical and radiologic resolution, and a shorter hospital stay.

Abstract Aims: We aimed to present successful endoscopic retrograde cholangiopancreatography (ERCP) applications and results in our pregnant cases. Method: The data of 14 successful ERCP applications in our pregnant patients between 2016 and 2022 were evaluated retrospectively. ERCP procedure was performed by endoscopists experienced in biliary endoscopy while the patients were on the left decubitus position. Fluoroscopy was performed using methods to reduce fetal radiation exposure. Short-term fluoroscopy were used during the procedure. Fluoroscopy times applied to the patient were recorded. Results: ERCP and sphincterotomy were applied to 14 pregnant women who presented with cholestasis findings. Two of the procedures were performed aproprate trimesters in whole patients. The mean maternal age in our pregnant women was 24.8±5.6 (19-38), mean gestational age was 17.8 weeks (10-34w). The fluoroscopy time was 0.16 min (0-35sec). Fetal radiation exposure was negligible in 10 pregnant women (10 sec) and between 10-14 seconds in 4 pregnant women. The estimated fetal radiation exposure of the two women was between 30 and 35 seconds. Procedure-related complications were one minimal bleeding after sphincterotomy, two hyperamylasemia after ERCP, and one acute respiratory distress syndrome. Cholecystitis developed in one pregnant woman two days after ERCP. Conclusion: When necessary precautions are taken under the control of a multidisciplinary team, ERCP can be safely applied during pregnancy, and successful results can be obtained.

Pregnancy is a dynamic state with multiple metabolic changes occurring including insulin resistance. Gestational diabetes mellitus (GDM), a form of diabetes that appears during pregnancy, develops if metabolic aberrations occur, in particular, in normal pregnancy-induced insulin resistance. Multi-omics is a powerful approach for uncovering the mechanisms driving metabolic change in different physiologic and pathologic states. A recent study demonstrated that the gestational gut microbiome mediates pregnancy metabolic adaptations through effects on gut indoleamine-2,3 dioxygenase 1 activity and the production of kynurenine. Using the dataset generated from this highly controlled study, we performed a comprehensive analysis of the pregnancy-specific physiological and metabolic profiles, 16S rRNA microbiome, and plasma untargeted LC-MS metabolome data. To facilitate the utilization of these analysis results by other researchers, we developed MOMMI-MP, a database that provides an easy-to-use platform to browse and search differential abundant microbial taxa and metabolites, and to examine metabolic pathways. The datasets consist of data collected from 3 genetically diverse strains of mice (C57BL/6J, CD1, and NIH-Swiss) over 6 time points during the gestational (days 0, 10, 15, and 19 during gestation) and postpartum (days 3 and 20 after delivery) states, totaling 180 samples for each strain. The computational results are presented in various tables and plots, and organized in MOMMI-MP to empower exploratory analyses by other researchers. In conclusion, MOMMI-MP is a resource to facilitate the investigation of novel mechanisms governing metabolic changes during pregnancy.

Leptospirosis is an important zoonotic disease, causing about 60,000 deaths annually. One of the reasons for the severe course of leptospirosis is a cytokine storm, which develops as a result of an excessive immune response. The gut microbiota that resides in the gastrointestinal tract provides essential health benefits to its host, particularly by regulating immune homeostasis and a bidirectional relationship with many internal organs. A change in the gut microbiota can be caused not only by antibiotics, but also by infectious agents such as the coronavirus or the flu virus. It is known that L. interrogans can change the microbiota of mice. Thus, gut dysbiosis in leptospirosis can affect the clinical course of the disease, through the gut–organ axis. Modulation of intestinal microbiota by probiotics and/or fecal microbiota transplantation in leptospirosis may become an important area of scientific research.

Liver cancers give rise to a heavy burden of health care worldwide. Understanding the tumour microenvironment (TME) underpins the development of precision therapy. Single-cell RNA sequencing (scRNA-seq) technology has generated high-quality cell atlases of the TME, but its wider application faces enormous costs for various clinical circumstances. Fortunately, a variety of deconvolution algorithms can instead repurpose bulk RNA-seq data, alleviating the need for generating scRNA-seq datasets. In this study, we reviewed major public omics databases for relevance in this study and utilized 8 RNA-seq and 1 microarray datasets from clinical studies. To decipher the TME of liver cancer, we estimated the fractions of liver cell components by deconvoluting the samples with Cibersortx using three reference scRNA-seq atlases. We also confirmed that Cibersortx can accurately deconvolute cell types/subtypes of interest. Compared with non-tumorous liver, liver cancers showed multiple decreased cell types forming normal liver microarchitecture, as well as elevated cell types involved in fibrogenesis, abnormal angiogenesis and disturbed immune responses. Survival analysis shows that the fractions of five cell types/subtypes significantly correlated with patient outcomes, indicating potential therapeutic targets. Therefore, deconvolution of bulk RNA-seq data with scRNA-seq atlas references can be a useful tool to help understand the TME.

Background and Aim: Spontaneous bacterial peritonitis is a common infection in liver cirrhosis. This systematic review and meta-analysis provides detailed information on the prevalence of SBP among HBV and HCV-related liver cirrhosis globally. Methods: A systematic search for articles describing the prevalence of SBP in HBV, and HCV related cirrhosis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Our search returned ten (10) eligible articles involving 1,713 viral cirrhosis cases representing eight (8) countries. A meta-analysis was performed on our eligible studies using the random effect model. A protocol was registered with PROSPERO (CRD42022321790). Results: The pooled prevalence of SBP in HBV associated cirrhosis had the highest estimate [8.0% (95% CI, 2.7 – 21.0%; I2= 96.13%; p < 0.001)], followed by SBP in HCV associated liver cirrhosis [4.0% (95% CI, 1.3% – 11.5%; I2 = 88.99%; p < 0.001)]. China (61.8%, CI: 57.1 – 66.3%), the USA (50.0%, CI: 34.6 – 65.4%), and Holland (31.1%, CI: 21.6 – 42.5%) had the highest estimate for SBP in HBV associated liver cirrhosis, SBP in HCV associated liver cirrhosis and SBP in HBV+HCV associated liver cirrhosis respectively. There was a significant difference in the prevalence of SBP in viral hepatitis-associated liver cirrhosis with the year of sampling and method of SBP detection at P<0.001. There was an increase in SBP incidence at the beginning of 2016 across the liver cirrhosis in this study. Conclusion: The findings of this review revealed an increase in the incidence of SBP in viral hepatitis over the last decade, the latter could be due to the global increase in Bacterial resistance. This indicates a possible future rise in the global prevalence of SBP among HBV, and HCV-related liver cirrhosis.

Probiotics are namely yeast and bacteria which are regarded as dietary supplements and food. Many probiotics are being commonly used now, the most frequently used, lactic acid bacteria are called Lactobacillus and Bifidobacterium. Many of the diseases associated with GIT are related to microbiota found in GIT, an imbalance of which causes gastrointestinal diseases. Probiotics, in light of scientific literature, are thought to play an important role in relieving symptoms of many diseases associated with GIT, i.e. beneficially regulating the microbiota composition. In the present review, we aimed to highlight the main considerations for main probiotic formulations to date. This study reviews the role of different probiotic formulations introduced so far in treating GI diseases in cohort ageing ≤18 years. We searched PubMed and Clinicaltrials.gov without any restrictions. This study comprises the descriptive and comparative analysis between Single-organism and Composite probiotics. These GI diseases include NEC, FAP, AGE, Acute Diarrhea, Ulcerative Colitis and etc. The results have been categorized according to title and outcomes. The positive outcomes emphasize the drug’s effectiveness in improving health and the negative outcome elaborates on the adverse effects the drug may have shown. Conclusively, discussed practices will assist in reducing GI disorders and strengthening the gut. Further insight into the various gut microbes and microbiomes with specific demographic is recommended.

Hepatitis B virus (HBV) is a major global health challenge. Emerging evidence suggests that poor knowledge and stigma are impacting HBV control efforts in sub-Saharan Africa (SSA), however their role is not well understood. We conducted a cross-sectional study of adults aged ≥ 18 years in a community and pharmacy setting in Freetown, Sierra Leone. A structured questionnaire was used to assess knowledge, stigmatizing attitudes, and health-seeking behaviors regarding HBV. Logistic regression was used to identify predictors of HBV knowledge and related stigma. A total of 306 adult participants were enrolled (50.7% male, 7.5% HBV positive and 11.7% vaccinated). Overall, 52.2% had comprehensive HBV knowledge and 49.3% expressed a stigmatizing attitude towards people with HBV. Notwithstanding, 72.2% stated they would receive the HBV vaccine if offered, 80.4% would take anti-HBV medication and 78.8% would be willing to attend clinic regularly. Comprehensive HBV knowledge was associated with HBV positive status (aOR 4.41; p = 0.029) and being vaccinated against HBV (aOR 3.30; p = 0.034). HBV-related stigma was associated with secondary or higher level of education (aOR 2.36; p &lt; 0.001), good HBV knowledge (aOR 2.05; p = 0.006) and pharmacy setting (aOR 1.74, p = 0.037). These findings suggest that education and stigma reduction may benefit HBV elimination efforts in SSA.

Background: Acute pancreatitis is a common emergency. Morbidity control requires early detection of disease severity. METHODS: A total of 131 AP patients were analyzed retrospectively. Patients were divided into two groups mild AP (MAP: Ranson score <3) and severe AP (SAP: Ranson score ≥3), according to Ranson’s criteria. Demographic data, hospitalization duration, PNI, CRP, and RDW levels were compared. Any p-value below 0.05 (p<0.05) was accepted as statistically significant. RESULTS: Study included 67 (51.15%) males and 64 (48.85%) females. The age average was 59.74 (19-90) years. 95 (72.52%) patients had MAP, and 36 (27.48%) patients had SAP. Mean hospitalization time, PNI, and CRP differed significantly between the two groups (p=0.010, p<0.05, p<0.05, respectively). The RDW (p=0.380) level difference was insignificant. For SAP prediction; the sensitivity, specificity and cut-off value according to Ranson code cut-off point for PNI were determined as 80.0% (95% CI:54.8-85.8), %72.2 (95% CI:70.5-87.5) and ≤45.6 (gr/L) + (mm3), respectively, and 94.7% (95% CI:57.8-87.9), %75.0 (95% CI:88.1-98.3) and >105,1 mg/L, respectively for CRP. CONCLUSION: PNI and CRP values (but not RDW values) were compatible with the disease severity determined by the Ranson criteria.

Intestinal gases are usually discarded as physiologically inert, useless sub-products of colonic fermentation that must be expelled to prevent discomfort and meteorism. Starting from the observation that many living beings use exogenous and/or endogenous gases to attain evolutionary benefits, we question whether intestinal gases in healthy humans could have underestimated physiological effects, either intestinal or extra-intestinal. We examine gaseous volume, composition, source and local distribution in proximal as well as distal gut, providing extensive data that may serve as reference for future studies. We analyze each one of the most abundant intestinal gases and describe their diffusive patterns, active trans-barrier transport dynamics, chemical properties, intra-/extra-intestinal metabolic effects mediated by intracellular, extracellular, paracrine and distant actions. Discussing the physical properties of the whole intestinal gaseous mixture, we illustrate how changes in volume/pressure can be generated by two different mechanisms, namely, physical muscular gut contraction and biological colonic fermentation, with quite different metabolic outcomes. The experimental gas laws suggest that the gaseous exchanges between lumen and bloodstream are impaired by muscular contraction and improved by muscular relaxation. In turn, the surface-area-to-volume ratio suggests that the gaseous exchanges are impaired by microorganismal overproduction and improved by microorganismal reduction. Further, theoretical stochastic approaches from probability theory indicate that the non-turbulent, random paths of gas molecules inside colonic haustra do not homogenously spread over the whole mucosal surface. This means that the intestinal area available for lumen/blood metabolic exchanges is much less than expected not just in disease states, but also in healthy individuals.

Facebook (FB) is the most popular online networking platform. There are several FB pages dedicated to spreading awareness about the Celiac disease (CD). To get the latest information, a huge number of CD patients follow Celiac disease Facebook (CD-FB) pages. Such pages frequently post beneficial information. However, very less is known if they provide appropriate information to CD patients. We conducted this study to know if CD-FB pages spread misleading information to CD patients. CD-FB pages from three celiac-influenced countries were explored using the FB platform and Google search engine. From October 2021 to April 2022, a total of 147 CD-FB, Italy (n=63), the USA (n=46), and India (n=38), were found eligible. Of them, 13% of pages (followers Mean±SD; Italy 2478±2011; USA 12635±12486; India 667±313) shared misleading information, particularly about gluten-free ingredients, and treatment of CD. In total,16% of CD-FB pages discussed alternative treatments option. Surprisingly, 7% of pages (followers Mean±SD; USA 23800±10465; India 628±333) supported alternative treatments for CD. CD-FB pages are useful for disseminating celiac-related information. While most of such pages provide useful information, a few pages sometimes contain misleading information. CD patients must consult their treating unit before following any uncertain information posted on CD-FB pages.

18F-fluorodeoxyglucose positron emission tomography and computed tomography (18F-FDG PET-CT) is increasingly used in the diagnosis, prognosis, staging, and treatment monitoring of many tumor types. However, only a small number of studies have reported the use of 18F-FDG PET-CT in intrahepatic cholangiocarcinoma (ICC). This study aimed to examine the accuracy of tumor staging in ICC by using 18F-FDG PET-CT. Between January 2009 and December 2020, patients with suspected ICC were retrospectively enrolled in the study and underwent imaging. The sensitivity and specificity of 18F-FDG PET-CT, CT, and magnetic resonance imaging (MRI) in detecting tumors, satellite focus, vascular invasion, and lymph node metastases were analyzed. The efficacy of 18F-FDG PET-CT for tumor staging was evaluated. Of the 110 patients who were enrolled in the study, 52 underwent surgical treatment and 45 were histologically diagnosed with ICC. When compared with CT or MRI, 18F-FDG PET-CT had similar sensitivity and specificity values for diagnosing satellite focus and vascular and bile duct invasion; however, PET-CT showed higher accuracy in diagnosing regional lymph node metastases. The accuracy of tumor staging by 18F-FDG PET-CT was higher than that by CT/MRI. Thus, 18FDG PET-CT may support tumor staging in ICC.

Functional gastro-intestinal disorders (FGID) including irritable bowel syndrome (IBS) are frequently handled by self-management with over the counter (OTC) products such as hyoscine butylbromide (HBB), alone or in combination with paracetamol, and natural products such as peppermint oil. To obtain real-world information, we have performed an anonymous pharmacy-based patient survey among 1686 users of HBB, HBB + paracetamol and peppermint oil. Based on the distinct but overlapping indications for the three OTC products, multiple logistic regression was applied to compare them in users reporting gastrointestinal cramps and pain, bloating, flatulence, or IBS as cardinal symptom. All three treatments reduced symptoms and associated impairments of work/daily chores, leisure activities, and sleep by approximately 50%. Based on the four cardinal symptoms and the four dependent continuous variables of interest (change of intensity of symptoms and of the three impairment domains) a total of 16 logistic regression models were applied. HBB, HBB + paracetamol, and peppermint oil had similar reported overall effectiveness in those models. Gender, age, baseline symptom severity and impairment in one of three domains had small and inconsistent effects on perceived treatment success. We provide evidence that HBB, HBB + paracetamol, and peppermint oil have comparable effectiveness in their approved indications under real-world conditions in an OTC setting.

Background: Stoma closure is a widely performed surgical procedure, with 6295 undertaken in England in 2018 alone. This procedure is associated with significant complications; incisional hernias are the most severe, occurring in 30% of patients. Complications place considerable financial burden on the NHS; hernia costs are estimated at GBP 114 million annually. As recent evidence (ROCSS, 2020) found that prophylactic meshes significantly reduce rates of incisional hernias following stoma closure surgery, an evaluation of this intervention vs. standard procedure is essential. Methods: A cost-utility analysis (CUA) was conducted using data from the ROCSS prospective multi-centre trial, which followed 790 patients, randomly assigned to mesh closure (n=394) and standard closure (n=396). Quality of life was assessed using mean EQ-5D-5L scores from the trial, and costs in GBP using UK-based sources over a 2-year time horizon. Results: The CUA yielded an incremental cost-effectiveness ratio (ICER) of GBP 128,356.25 per QALY. Additionally, two univariate sensitivity analyses were performed to test the robustness of the model. Conclusion: The results demonstrate an increased benefit with mesh prophylaxis, but at an increased cost. Although the intervention is cost-ineffective and greater than the ICER threshold of GBP 30,000/QALY (NICE), further investigation into mesh prophylaxis for at risk population groups is needed.

(1) Background: Heavy and chronic alcohol intake causes altered gut-permeability and dysfunction; and exhibits a unique pro-inflammatory state. Thyroid-associated hormones and proteins may be dysregulated by alcohol administration; however, the impact of altered gut-derived changes on thyroid function is unclear. This study investigated the role of gut-dysfunction and pro-inflammatory activity on thyroid function in patients with alcohol use disorder (AUD). (2) Methods: Male and female AUD patients (n=44) were grouped as Gr.1 with normal thyroid stimulating hormone (TSH) levels (n=28, 0.8≤TSH≤3 mIU/L); and Gr.2 with clinically elevated TSH levels (n=16, TSH&gt; 3 mIU/l). Demographics, drinking measures, comprehensive metabolic panel, and candidate thyroid markers (TSH, circulating triiodothyronine [T3] and free thyroxine [fT4]) were tested. Plasma-derived gut-dysfunction associated markers (lipopolysaccharide [LPS], LPS-binding protein [LBP], and LPS-induced pathogen-associated protein [CD14]), and cytokine profile (IL1-β, TNF-α, IL-6, IL-8, MCP-1, PAI-1) were analyzed and compared with the thyroid, demographic, and drinking markers. (3) Results: Both groups presented with a borderline overweight category of BMI. Gr.2 presented with numerically higher level of chronic and heavy drinking patterns vs Gr.1. fT4 levels were elevated while T3 was within normal limits in both the groups. Gut-dysfunction markers LBP and CD14 were numerically elevated in Gr.2 vs Gr.1 suggesting subtle ongoing changes; however, the difference was not statistically significant. All pro-inflammatory cytokines were significantly elevated in Gr.2 among IL1-, MCP-1, and PAI-1. Gr.2 showed a strong and statistically significant effect of gut-immune-pituitary response (r=0.896, p=0.002) on TSH levels in a multivariate regression model with LBP, CD14, and PAI-1 levels as upstream variables; this assessment was not significant in Gr.1. In addition, AUROC analysis demonstrated that many of the cytokines strongly predicted TSH in Gr.2, including IL-6 (area=0.774, p&lt;0.001) and TNF- (area=0.708, p=0.017) among others. This was not observed in Gr.1. Gr.2 demonstrated elevated fT4 as well as TSH, which suggests that there was subclinical thyroiditis with underlying CNS dysfunction and lack of a negative feedback loop. (4) Conclusions: These findings reveal the toxic effects of heavy and chronic drinking that play a pathological role in thyroid gland dysregulation employing the gut-brain axis. These results also strongly emphasize potential directions to strongly consider thyroid dysregulation in the overall medical management of AUD.

Recent advancements in surgical and anti-cancer therapies have provided significant hope of long survival in patients with pancreatic cancer (PC). To realize this hope, routine medical checkups of asymptomatic people should be performed to identify operable PCs. In this study, we evaluated the efficacy of medical checkups using abdominal ultrasonography (US). We retrospectively analyzed 374 patients with PC at our institute between 2010 and 2021. We divided these patients into several groups according to the diagnostic approach and compared their background and prognosis. These groups comprised PCs diagnosed through (a) symptoms, 242 cases; (b) US during medical checkup for asymptomatic individuals, 17; and other means. Of the 375 patients, 192 were men (51.3%), and the median age was 74 years (34–105). Tumors were located in the pancreatic tail in 67 patients (17.9%). Excision ratio and 5-year survival rate were significantly better in group (b) than in (a) (58.8% vs. 23.1%, P<0.01 and 42.2% vs. 9.4%, P<0.001, respectively). The prognosis of patients diagnosed using US during medical checkup was better than that of patients identified through symptomatic presentation of PC. US for asymptomatic individuals with PC might be useful for promoting better prognosis of PCs.

COVID-19 and long COVID-19 vulnerabilities may be caused indirectly by albumin binding deficiency (ABD) which can be corrected by the correct administration of human serum albumin (HSA). The liver is the primary site of nutrient regulation and fluid volume maintenance, control of both is by changes to albumin concentration. In healthy subjects the HSA lymphatic nutrient pump (HSALNP) ensures continual pumping of nutrients from the liver are appropriately distributed to organs. Nutrients are delivered to cells according to the availability of binding to HSA. The HSALNP therefore maintains the correct nutrients and colloidal pressure balance in all tissues independently. In unhealthy tissues, following COVID-19 infection, the passage of HSA/nutrients through the interstitial spaces and lymph will be impeded. Fluid therapy into the periphery leads to dilution of essential nutrients attached to the protein-carriers such as albumin. The levels of albumin being charged by the liver with nutrients is critical in maintaining immune stability by maintaining nutrient support and colloidal pressure of cellular structures. The site of HSA binding by the liver is of great importance and direct infusion of albumin into the Hepatic Portal Vein is the most appropriate method of maintaining colloid pressure and cellular nutrient levels.

BACKGROUND&AIMS: Hepatitis B virus (HBV) infection remains a major public health problem. The interaction between HBV and the host inflammatory response is an important factor contributing to liver damage and disease development. We compared the correlation between the subclinical index and PBMCs concentration in two groups of pregnant women (HBsAg positive), which are different in HBV DNA concentration in Vietnam. METHODS: The Hierarchical cluster analysis (HCA) was run with 20 different clustering methods on data collected from 80 Vietnamese pregnant women and their babies (60/80 cord blood). RESULTS: In the high viral load group (HBV DNA ≥ 5x10^7 copies/ml), a strong correlation between CBMCs with serum maternal Haemoglobin concentration and maternal platelet and maternal ALT. Their R values are: -0.88, 0.82, and 0.84 with p=8.97E-03, 2.41E-02 and 1.75E-01, respectively. CONCLUSIONS: We found a significant correlation shift of subclinical index between the two groups, which may be important in diagnosing pregnant women with chronic hepatitis B virus infection.

Celiac disease (CD) is an autoimmune disorder triggered by gluten ingestion in genetically predisposed individuals. In addition to the typical gastrointestinal symptoms such as diarrhea, bloating, or chronic abdominal pain, CD may also present a wide spectrum of manifestations, including low bone mineral density (BMD) and osteoporosis. This review aims to describe the role of CD in the development of skeletal alterations, underlying important clinical aspects and therapeutic implications. The etiopathology of bone lesions in CD is multifactorial and their management is challenging. Here, we provide gastroenterologists and orthopedics with an up-to-date overview on the link between CD and osteoporosis to improve the management of the CD condition.

To describe the metabolic effect of cholecystokinin and its relationship with post-bariatric sugery patients. Methodology: This is a qualitative analysis in the form of integrative literature review, the theme chosen clearly and explicitly: "What is the metabolic profile of cholecystokinin and its effect on post-bariatric sugery patients?". After formulating the guiding question, the following keywords in Portuguese, English and Spanish were chosen: "bariatric surgery", "bariatric surgery", "cirugía bariátrica"; "cholecystokinin", "cholecystokinin", "cholecystokinin"; "fome", "hunger", "hambre"; "satiety response", "satiety response", "respuesta de saciedad", "Roux-en-Y anastomosis", "anastomosis Roux-en-Y", and "anastomosis en-Y de Roux", through the combination of the controlled descriptors, Medical Subjetc Heading (MeSH) and the Health Science Descriptors (DeCS) resources, as well as the Boolean operators "AND" and "OR". In the databases Latin American and Caribbean Literature on Health Sciences (LILACS), Virtual Health Library (VHL), PubMed, Scientific Electronic Library Online (SciELO) and Google Scholar, a search for clinical trials conducted in humans from 2012 to 2022 was performed. Results: 2,038 articles were identified. The final sample of this review consisted of eleven scientific articles; of these, four were found in the VHL database, two in PubMed, and five in Google Scholar. Thus, concepts about the digestion process and the hormones involved, bariatric surgery techniques and their hormonal effects, were observed in each of the selected articles. Conclusions: Cholecystokinin, a gastrointestinal hormone, is one of the major endocrine satiety signals. It is observed that with gastroplasty, the levels of the hormone CCK are elevated; thus, besides increasing satiety, cholecystokinin aids in weight loss. Therefore, bariatric surgery is highly effective in improving the patient's quality of life

Hepatitis is the eighth highest cause of mortality globally and second-highest in Pakistan. The purpose of this study was to determine frequency of Hepatitis B and C and related lifestyle and socio-demographic risk factors among adults. The data were collected though questionnaire from Hepatitis B and C patients from Mayo and Jinnah hospital Lahore. The data was analyzed using SPSS version 18. There were 5095 patients with Hepatitis B and C out of which 146 patients (67 males and 79 females) filled questionnaire. The frequency of hepatitis C was higher than hepatitis B. The significant risk factors associated with hepatitis B and C were education, marital status, family history, household income, and type of food consumed. Therefore, socio-demographic and lifestyle risk factors related interventions are needed to reduce frequency of Hepatitis B and C.

Background: Studies have demonstrated the link between vitamin D-related genetic variations and non-skeletal outcomes. We aimed to identify all available data on the association of vitamin D-related genetic variations with non-alcoholic fatty liver disease (NAFLD). Methods: Potentially eligible studies were identified from Embase and Medline databases from inception to June 2022 using search strategy that comprised terms for “Vitamin D” and “NAFLD”. Eligible study must report the association between vitamin D-related genetic variations and presence, severity or response to treatment of NAFLD. Data were extracted from each eligible study. Results: A total of 3,495 articles were identified. After systematic review, twelve studies were in-cluded. A total of 26 genetic variations were identified. Presence of NAFLD was associated with variations of GC (rs222054, rs222020, rs10011000, rs7041), VDR (rs2228570, rs11168287, rs10783219, rs4752), CYP24A1 (rs3787557, rs6068816, rs2296241, rs2248359) and CYP27B1 (rs4646536). Severity of NAFLD was associated with variations of GC (rs4588), VDR (rs2228570, rs4334089), CYP2R1 (rs10741657), DHCR7 (rs1544410, rs3829251, rs12785878) and CYP24A1 (rs3787557, rs6068816, rs6097809, rs6127119, rs2248359, rs3787554, rs4809960, rs6022999). Response to calcitriol treatment was associated with variation of VDR (rs10735810). Conclusions: Multiple vitamin D-related genetic variations were associated with NAFLD, indi-cating the role of vitamin D in the pathogenesis of NAFLD.

Management of inflammatory bowel disease (IBD) often relies on biological and immunomodulatory agents for remission through immunosuppression, raising concerns regarding the SARS-CoV-2 vaccine's effectiveness. The emergent variants have hindered the vaccine neutralization capacity, and whether the third vaccine dose has the capacity to neutralize SARS-CoV-2 variants in this population remains unknown. This study aims to evaluate the humoral response of SARS-CoV-2 variants in patients with IBD 60 days after the third vaccine dose [BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)].56 su bjects with IBD and 12 healthy subjects were recruited. 90% of patients with IBD (49/56) were receiving biologics and/or immunomodulatory therapy. 24 subjects with IBD did not develop effective neutralizing capability against the Omicron variant. 70% (17/24) of those subjects were receiving anti-Tumor Necrosis Factor therapy [10= adalimumab, 7= infliximab], two of them had a history of COVID-19 infection, and one subject did not develop immune neutralization against three other variants: Gamma, Epsilon, and Kappa. All subjects in the control group developed detectable antibodies and effective neutralization against all seven SARS-CoV-2 variants. Our study shows that patients with IBD might not be protected against SARS-CoV-2 variants, and larger studies are needed to evaluate optimal immunity.

Background: Transarterial chemoembolization (TACE) is the standard treatment for BCLC-B hepatocellular carcinoma (HCC). A novel glass membrane emulsification device (GMD) produces a high percentage of water/oil emulsions with homogeneous and stable droplets. There are few reports on the efficacy of GMD-conventional-TACE (GMD-c-TACE)；therefore, we aimed to evaluate the effectiveness of GMD-c-TACE. Methods: Seventy-one patients with HCC with tumor diameter <5 cm who underwent c-TACE with and without GMD were included in this study to investigate local recurrence and hepatic functional reserve. Results: The local recurrence rates of TACE without GMD were 3.0% at 6 months, 16.7% at 12 months, and 35.0% at 18 months, around where it plateaued. Hence, the local recurrence rates in the GMD-c-TACE group were 7.7% at 14 months and 23.1% at 20 months, respectively. Thus, GMD-c-TACE had a significantly lower local recurrence. Multivariate analysis showed that GMD-c-TACE could suppress local recurrence and maintain hepatic reserve. Conclusions: GMD-c-TACE allows dense lipiodol accumulation in the tumor and attainment of good local control. Additionally, the inhibition of the release of anticancer drugs may maintain hepatic reserve. GMD-c-TACE is useful in preventing local recurrence and is expected to become the standard treatment form of c-TACE in the future.

BACKGROUND. Two sequelae of non-alcoholic steatohepatitis (NASH), ESLD and HCC, have become the leading causes for liver transplantation in the Western. The present study aims to approach the cellular metabolic disturbances involved in NASH progression that are associated with microbiota community changes. METHODS. Metabolic effects and microbiota community changes were explored in the murine with NASH progression by blocking the Na/K-ATPase/Src/reactive oxygen amplification loop using the synthetic targeting peptide pNaKtide. DNA from the terminal ileum microbiota habitat was obtained and amplified by PCR to develop DNA bacterial phylogenic sequence analysis of wild type and treated animals at 12, 24 and 48 weeks. Induced changes by pSrc normalization at 24 weeks were correlated with liver morphological changes, intestinal CD4+/CD8+ ratio, and liver macrophage CD14+ expression. Differences among groups were evaluated by ANOVA/t-test and Principal Component Analysis (PCA). RESULTS. Microbiota communities varied significantly at all time points (12, 24 and 48 weeks), with an increase of Verrucomicrobia and a decrease of Bacteroidetes and Firmicutes in the HFD group. Microbiota community changes regressed to their wild-type state at 24 weeks on treated animals, and those changes were associated with a decrease in liver inflammation and senescence, lower ileum CD4+/CD8+ T cells and higher liver CD14+ cells (p<0.05). Concomitantly, the metabolic disturbances in our diet-induced NASH model were normalized by NKA/Src signaling blockage and exercise with a paucity of apoptotic activity, mitigation of cell senescence, and regression of liver fibrosis (p<0.01). CONCLUSIONS. pSrc inhibition at caveolar α1-Na/K-ATPase rescinded NASH-related metabolic disturbances establishing resident physiological microbiota communities with concomitant paucity on apoptotic activity and regression of liver fibrosis; effects that were associated with both gut and liver T-lymphocyte responses.

Background: Crohn’s and Ulcerative Colitis Questionnaire-32 (CUCQ-32) is a validated questionnaire to measure the quality of life (QoL) in inflammatory bowel disease (IBD). However, it does not have stoma specific questions and can be lengthy. This study aimed to validate a subset of the CUCQ-32 that would be suitable for patients with a stoma. Methods: Baseline data were collected from a cohort of patients with acute ulcerative colitis who were participating in the CONSTRUCT multi-centre clinical trial. A subset of the CUCQ-32 questions was selected by stepwise regression. Further validation was examined using data from the UK IBD biological therapies audit. Construct validity was carried out using the EuroQol 5 dimensions (EQ5D) questionnaire, Simple Clinical Colitis Activity Index (SCCAI) and the Harvey-Bradshaw Index (HBI). Literature review and an expert focus group identified supplementary questions to cover patients with a stoma. Test-retest analysis was done during the patients’ second follow up visits. Results: Using the data from 124 patients, a short version questionnaire (CUCQ-12) was developed. Further validation using data from 484 patients with IBD as part of the UK IBD biological therapies audit. Using the data from 61 patients with a stoma, we identified 5 stoma specific questions for the CUCQ-12+. The CUCQ-12+ demonstrated excellent internal consistency (Cronbach’s α= 0.86); established effective reproducibility (intra-class correlation coefficient= 0.74); correlated well with the EQ5D (r= - 0.48), HBI (r= 0.45) and SCCAI (r= 0.43); and represented good responsiveness statistics (>0.5). Conclusions: CUCQ-12+ is a valid and reliable QoL measure that can be used for all patients with IBD in clinical practice including patients with a stoma.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Sustained hepatic inflammation is a key driver of the transition from simple fatty liver to nonalcoholic steatohepatitis (NASH), the more aggressive form of NAFLD. Hepatic inflammation is orchestrated by chemokines, a family of chemoattractant cytokines, which are produced by hepatocytes, Kupffer cells (liver resident macrophages), hepatic stellate cells, endothelial cells, and vascular smooth muscle cells. Over the last three decades, accumulating evidence from both clinical and experimental investigations demonstrated that chemokines and their receptors are increased in the livers of NAFLD patients and that CC chemokine ligand (CCL) 2 and CCL5, in particular, play a pivotal role in inducing insulin resistance, steatosis, inflammation, and fibrosis in the liver disease. Cenicriviroc (CVC), a dual antagonist of these chemokine’s receptor, CCR2 and CCR5, has been tested in clinical trials in patients with NASH-associated liver fibrosis. Additionally, recent studies revealed that other chemokines, such as CCL3, CCL25, CX3C chemokine ligand 1 (CX3CL1), CXC chemokine ligand 1 (CXCL1), and CXCL16 can also contribute to the pathogenesis of NAFLD. Here, we review recent updates on the roles of chemokines in the development of NAFLD and their blockade as potential therapeutic approaches.

Thyroid hormones, their metabolites and synthetic analogues are potential anti-steatotic drug candidates considering that subclinical and manifest hypothyroidism is associated with hepatic lipid accumulation, non-alcoholic fatty liver disease, and its pandemic sequelae. Thyromimetically active compounds stimulate hepatic lipogenesis, fatty acid beta-oxidation, cholesterol metabolism and metabolic pathways of glucose homeostasis. Many of these effects are mediated by T3 receptor β1-dependent modulation of transcription. However, rapid non-canonical mitochondrial effects have also been reported, especially for the metabolite 3,5-diiodothyronine (3,5-T2), which does not elicit the full spectrum of “thyromimetic” actions inherent to T3. Most preclinical studies in rodent models of obesity and first human clinical trials are promising with respect to the antisteatotic hepatic effects, but potent agents exhibit unwanted thyromimetic effects on the heart and/or suppress feedback regulation of the hypothalamus-pituitary-thyroid-periphery axis and the fine-tuned thyroid hormone system. This review focusses on 3,5-T2 effects on hepatic lipid and glucose metabolism and (non-)canonical mechanisms of action including its mitochondrial targets. Various high fat diet animal models with distinct thyroid hormone status indicate species- and dose-dependent efficiency of 3,5-T2 and its synthetic analogue TRC150094. No convincing evidence has been presented for their clinical use in prevention or treatment of obesity and related metabolic conditions.

Several clusters and individual cases of acute —often severe— hepatitis have been reported in Europe —mainly in the United Kingdom (U.K.)—, the United States (U.S.) and recently in Asia since October 2021. Laboratory investigation of the common viral hepatitis agents (HAV, HBV, HCV, HDV and HEV) yielded negative results prompting the use of the term “acute non hepA–E hepatitis” to describe this condition. The cases were characterized by the manifestations of acute hepatitis (abdominal pain, vomiting, diarrhea, jaundice and very high levels of liver enzymes) affecting children with a median age of 3–4 years. The exact underlying etiology has not been revealed yet; however, a leading hypothesis is that an infectious agent is the culprit underlying cause or at least a risk factor for acute non hepA–E hepatitis occurrence. So far, laboratory testing has shown the presence of adenovirus serotype 41 (Ad–41) which is classified in group F of adenoviruses in about three-fourths of the reported cases. However, the definitive link between adenoviruses and acute non hepA–E hepatitis has not been fully elucidated, which necessitates further investigation of this possible correlation. As of the end of April 2022, more than 200 cases were reported worldwide, the majority of which were in Europe: the U.K. (n=114), Italy (n=17), Spain (n=13), Israel (n=12), the U.S. (n=9), Denmark (n=6), Netherlands and Ireland (n=4), Japan (n=3), Austria, Belgium, France, and Norway (n=2), Germany, Poland, and Romania (n=1). Possible cases are being evaluated in Illinois, Minnesota, North Carolina, Wisconsin states of the U.S., Canada, Singapore and Slovenia. Vigilant surveillance and epidemiologic investigation to identify further cases are warranted at the global level to delineate the features of this emergent public health issue. The possible role of environmental and toxic agents including foodborne toxins should not be overlooked as well. Specific guidelines for identification of further cases is necessary particularly in low-income settings where testing for adenoviruses is not considered routinely. Genetic analysis of Ad–41 isolates is recommended to assess the potential changes in virus genome with subsequent possible altered virus behavior. Immunopathogenesis is another possibility that should be examined as well considering the absence of virus detection in liver biopsies of the affected children in the U.S.

Inflammatory bowel disease (IBD) is a chronic and relapsing disease caused by a dysregulated immune response to host intestinal microbiota that occurs in genetically predisposed individuals. IBD encompasses two major clinical entities: ulcerative colitis (UC), which is limited to the colonic mucosa, and Crohn disease (CD), which might affect any segment of the gastrointestinal tract. Despite the prevalence of IBD is increasing worldwide, therapy remains suboptimal, largely because the variability of causative mechanisms, raising the need to develop individualized therapeutic approaches targeted to each individual patient. In this context, patients-derived intestinal organoids represent an effective tool for advancing our understanding on IBD’ s pathogenesis. Organoid 3D culture systems offer a unique model for dissecting epithelial mechanisms involved IBDs and test individualized therapy, although the lack of a functional immune system and a microbiota, two driving components of the IBD pathogenesis, represent a major barrier for their exploitation in clinical medicine. In this review we have examined how to improve the translational utility of intestinal organoids in IBD and how co-coltures of 3D or 2D organoids and immune cells and/or intestinal microbiota might help to overcome these limitations.

Olfactory Receptors (ORs) are a large family of G protein coupled receptors predominantly expressed by the main olfactory epithelium at nasal level and are responsible for the generation of smelling sense. Microarray and deep sequencing analyses, however, have demonstrated that ORs are ectopically expressed in various human tissues including testis, kidneys, adipose tissue and liver and their biological functions become to be unrevealed. Molecular and pharmacological approaches have shown that some of these ORs modulate glucose and lipid metabolism at multiple interfaces, suggesting that ORs might be part of the large family of nutrient sensors. i.e. molecular/ cellular machines that respond to a specific nutrient component. By using nutrients- derived agonists it has been shown that ORs effectively modulates glucose and lipid metabolism raising interest on their possible therapeutic application in the treatment of metabolic disorders including dyslipidemia, obesity and metabolic syndrome.

Cancer stem cells (CSCs) are a tumor cell subpopulation that drives tumor progression and metastasis, leading to poor overall survival of patients. In colorectal cancer (CRC), hyper-activation of Wnt/β-catenin signaling by mutation of both Adenomatous polyposis coli (APC) and K-Ras increases the size of the CSC population. We previously showed that the CPD0857 inactivates Wnt/β-catenin signaling by promoting ubiquitin-dependent proteasomal degradation of β-catenin and Ras proteins, thereby decreasing proliferation and increasing apoptosis of CRC lines. CPD0857 also decreased growth and invasiveness of CRC cells harboring mutant K-Ras resistant to EGFR mAb therapy. Here, we show that CPD0857 treatment decreases proliferation and increases neuronal differentiation of neural progenitor cells (NPCs). CDP0857 effectively reduced expression of CSC markers and suppressed self-renewal capacity. CPD0857 treatment also inhibited proliferation and expression of CSC markers in D-K-Ras MT cells carrying K-Ras, APC and PI3K mutations, indicating inhibition of PI3K/AKT signaling. Moreover, CPD0857-treated xenograft mice showed regression of tumor growth and decreased numbers of CSCs in tumors. We conclude that CPD0857 could serve as the basis of a drug development strategy targeting CSCs activated through Wnt/β-catenin-Ras MAPK-PI3K/AKT signaling in CRCs.

Purpose: To assess the utility of measurement of the computed tomography (CT) attenuation value (CTav) in predicting tumor necrosis in hepatocellular carcinoma (HCC) patients who achieve a complete response (CR), defined using modified Response Evaluation Criteria in Solid Tumors (mRECIST), after lenvatinib treatment. Method: We compared CTav in arterial phase CT images with postoperative histopathology in four patients who underwent HCC resection after lenvatinib treatment, to determine CTav thresholds indicative of histological necrosis (N-CTav). Next, we confirmed the accuracy of the determined N-CTav in 15 cases with histopathologically proven necrosis in surgical specimens. Furthermore, the percentage of the tumor with N-CTav, i.e. the N-CTav occupancy rate, assessed using Image J software in 30 tumors in 12 patients with CR out of 571 HCC patients treated with lenvatinib, and its correlation with local recurrence following CR were examined. Results: Receiver operating characteristic (ROC) curve analysis revealed an optimal cut-off value of CTav of 30.2 HU, with 90.0% specificity and 65.0% sensitivity in discriminating between pathologically identified necrosis and degeneration, with a CTav of less than 30.2 HU indicating necrosis after lenvatinib treatment (N30-CTav). Furthermore, the optimal cut-off value of 30.6% for the N30-CTav occupancy rate by ROC analysis was a significant indicator of local recurrence following CR with 76.9% specificity and sensitivity (area under the ROC curve; 0.939), with the CR group with high N30-CTav occupancy (&gt;30.6%) after lenvatinib treatment showing significantly lower local recurrence (8.3% at 1 year) compared with the low (&lt;30.6%) N30-CTav group (P&lt;0.001, 61.5% at 1 year). Conclusion: The cut-off value of 30.2 HU for CTav (N30-CTav) might be appropriate for identifying post-lenvatinib necrosis in HCC, and an N30-CTav occupancy rate of &gt;30.6% might be a　predictor of maintenance of CR. Use of these indicators have the potential to impact systemic chemotherapy for HCC.

Objective: The study aimed to manage and to analyse the results of the laboratory tests, available nowadays, used from routine clinical practice, for screening of hepatitis C. Methods: comparison of ELISA method results (Enzyme-Linked Immunosorbent Assay) and chemiluminescence methods results. Beside previously mentioned, the study show the structural comparison of normal liver and pathologic liver with hepatic cirrhosis, using permanent samples colored after the technique protocol. Statistical analysis of this study results, was performed using the laboratory informatic system. Results: The results of the study are substantial and intricate. For this purpose, the results of preliminary EСL screening method of patients at risk for HCV who took part in the study, are presented in tables and figures. Results of this study are various and are correlate from different perspectives. Also good to mention that the correlations of results were used in order to identify a possible relationships between indicators of ELISA method and ECL index. More than, correlations antibodies detected in ECL and ELISA are point out. Conclusion: EСL and ELISA method results, are relevant for screening and for diagnostic confirmation in HCV risk patients. Unfotunately in the present study, were impossible to conclude about false-negative results. Good to know our opinion that RT-PCR technique, it is considered proper for the diagnosis of HCV.

The diagnosis of celiac disease (CD) may be delayed due to non-specific clinical symptoms. The aim of the study was to evaluate the clinical manifestation and diagnostic process of CD in Polish children and adults. Methods: The members of the Polish Coeliac Society (n=2 500) were asked to complete a questionnaire on socio-demographic factors, clinical and diagnostic aspects of CD. The analysis was based on 796 responses from patients with confirmed CD diagnosis, and included 224 (28.1%) children and 572 (71.9%) adults. Results: The mean duration of symptoms prior to CD diagnosis in children was significantly shorter than in adults (p < 0.001), and amounted to 3.1 and 9 years respectively. The most frequent symptoms before CD diagnosis were abdominal pain and bloating in children (70.4%), and chronic fatigue in adults (74.5%). Although almost all CD patients claimed to strictly avoid gluten after CD diagnosis, symptoms were still present in the majority of these respondents. No comorbid diseases were reported by 29.8% of children and by 11.7% of adults (p < 0.001). Conclusions: The results indicate that CD diagnosis is delayed in Poland, espe-cially in adults, and clinicians should be aware of the diversity in CD presentation.

Patients in intensive care unit often lose a considerable fraction of their gut microbiome due to exposure of broad-spectrum antibiotics and other reasons. Dysbiosis often results in prolonged diarrhea and increase occurrence of multi-drug resistant pathogens in the colon with clinical consequences not yet well understood. Restoring the microbioma by faecal microbial transplantation (FMT) is a plausible therapeutic possibility, so far only documented in case reports and case series using very heterogeneous methodologies. Before FMT in critically ill can be tested in randomised controlled trials, there is a burning need to describe a standardized operating procedure (SOP) of the whole process, respecting the specifics of critically ill population, such as the risk of disrubted intestinal barrier and time critical nature of the procedure. We describe the SOP that has been developed for experimental use in critically ill patients by a multidisciplinary team of intensivists, gastroenterologist and microbiologist based on feedback from regulatory authority (State Institue of Drug Control of the Czech Republic). The hallmarks of these SOPs are multi-donor freshly frozen transplantate quaranteeded for 3 months consisting of 7 aliqutes from 7 unrelated healthy donors, and administered by rectal tube. In this paper we discuss the rationale for this SOP and the process of its development in details and release the full proposed SOP is in the form of online appendix.

Background and Aims: Of all primary liver tumors, primary hepatic angiosarcoma (PHA) is a rare and aggressive malignant vascular tumor. The standard therapeutic care for hepatic angiosarcoma remains unclear. This study compared the survival outcomes of aggressive treatment (resection and liver transplant) and nonaggressive treatment (chemotherapy, transarterial chemoembolization [TACE], and conservative treatments) for patients with PHA and analyzed the prognostic factors influencing survival. Materials and Methods: Data of patients diagnosed as having PHA at our facility were retrospectively reviewed. The primary outcome was survival time. The secondary outcome was calculated baseline characteristics. Results: We included a total of 19 patients, who were divided into 2 treatment groups: aggressive (8 patients had undergone resection or transplants) and nonaggressive (11 patients had undergone TACE, chemotherapy, or conservative treatment). The mean survival time was 233.1 ± 189.7 days in the aggressive treatment group and 146.5 ± 115.8 days in the nonaggressive treatment group. A Kaplan-Meier plot revealed no significant difference in survival time between the 2 treatment groups (P = .3256). Conclusions: The survival time of patients receiving aggressive treatment was longer than that of those receiving nonaggressive treatment. The long term survival time in some selective cases of aggressive treatment will be achieved. Thought a difference was not significant between the groups. Because the number of patients was limited, more cases are required to confirm these findings.

Helicobacter pylori is the most common human gastric infection. H. pylori stool antigen lateral flow immunochromatography assay (HpSA-LFIA) is considered one of the most cost-effective and rapid non-invasive assays (active tests). The evaluation of this test is crucial for accuracy and utility assurance. This study aimed to evaluate the polyclonal antibody-based HpSA-LFIA in comparison to a monoclonal antibody-based ELISA kit. Methodology: Stool samples were collected from 200 gastric patients for HpSA-LFIA and semi-quantitative HpSA-ELISA. Statistical analysis of the diagnostic values was performed using MedCalc software. Chi-square tests were used to determine the effects of gender and age. Results: The obtained results found that HpSA-LFIA achieved promising sensitivity (93.75%) and NPV (98.00%). However, it had poor specificity, PPV, and accuracy, respectively, 59.76%, 31.25%, and 65.31%. LR+ & LR- were 2.33% & 0.1%, respectively. Gender had no significance on the di-agnostic parameters of HpSA-LFIA. Age groups had irrelevant sensitivity; however, specificity was significantly higher in patients over 45 years. Conclusion: It was concluded that HpSA-LFIA was not accurate enough to be the sole test for di-agnosis and needs other confirmatory tests in case of positive conditions

Pancreatitis and alcoholic pancreatitis are serious health concerns, and there is an urgent need for effective treatment strategies. Alcohol is a known etiological factor for pancreatitis, including acute pancreatitis (AP) and chronic pancreatitis (CP). Excessive alcohol consumption induces many pathological stress responses; of particular note is endoplasmic reticulum (ER) stress and adaptive unfolded protein response (UPR). ER stress results from the accumulation of unfolded/misfolded protein in the ER and is implicated in the pathogenesis of alcoholic pancreatitis. Here we summarize the possible mechanisms by which ER stress contributes to alcoholic pancreatitis. We also discuss potential approaches targeting ER stress and UPR for developing novel therapeutic strategies for the disease.

Huge effort has been devoted to developing drugs targeting integrins over 30 years, because of the primary roles of integrins in the cell-matrix milieu. Five αv-containing integrins, in the 24 family members, have been a central target of fibrosis. Currently, a small molecule against αvβ1 is undergoing a clinical trial for NASH-associated fibrosis as a rare reagent aiming at fibrogenesis. Latent TGFβ activation, a distinct talent of αv-integrins, has been intriguing as therapeutic target. None of the αv-integrin inhibitors, however, has been in the clinical market. αv-integrins commonly recognize an Arg-Gly-Asp (RGD) sequence, and thus the pharmacophore of inhibitors for the 5-integrins is based on the same RGD structure. The RGD preference of the integrins, at the same time, dilutes ligand specificity, as the 5-integrins share ligands containing RGD sequence such as fibronectin. With the inherent little specificity in both drugs and targets, “disease specificity” has become less important for the inhibitors than blocking as many αv-integrins. In fact, an almighty inhibitor for αv-integrins, pan-αv, was in a clinical trial. On the contrary, approved integrin inhibitors are all specific to target integrins, which are expressed in cell-type specific manner: αIIbβ3 on platelets, α4β1, α4β7 and αLβ2 on leukocytes. Herein, “disease specific” integrins would serve as attractive targets. α8β1 and α11β1 are selectively expressed in hepatic stellate cells (HSCs) and distinctively induced upon culture activation. The exceptional specificity to activated HSCs reflects rather “pathology specific” nature of these new integrins. The monoclonal antibodies against α8β1 and α11β1 in preclinical examinations may illuminate the road to the first medical reagents.

Background: HMGA2 encodes a small non histone chromatin-associated protein that has no intrinsic transcriptional activity, but can modulate transcription by altering the chromatin architecture. HMGA2 was found overexpressed in a variety of epithelial and mesenchymal tumors and promoted invasion and metastasis in most malignant epithelial tumors. A recent study showed that P53 inhibited CRC progression by targeting HMGA2. However, the mechanism by which HMGA2 affect angiogenesis in CRC has not been clarified. Methods: The expression of HMGA2 was analyzed by IHC, WB and bio infomatic analysis. Cbioportal and mexpress online tools were applied to explore the CNV and methylation of HMGA2 in CRC patients. Single cell data from GEO was used to examine the specific cell type that contribute to the high HMGA2 expression in CRC. Lentivirus was used to knock down HMGA2 in CRC cells and HUVECs was used to study angiogenesis. Results: In the current study, we first detected the expression pattern of HMGA2 in CRC patients and evaluated its clinical values and CNV amplification could possibly contribute to the up regulation of HMGA2 in CRC patients. By analyzing CRC single cell data we found that HMGA2 was specifically up regulated in the colorectal epithelial cells. Furthermore, knocking down of HMGA2 suppresses angiogenesis via dual regulation of VEGF-A and SEMA3A in CRC through inactivating VEGRR2 pathway in HUVECs. Conclusions: HMGA2 might be a promising prognostic marker and target for treating advanced CRC patients.

A growing body of evidences is showing that dysbiotic gut microbiota may correlate with a wide range of disorders; hence, the clinical use of microbiota maps and fecal microbiota transplantation (FMT) can be exploited in the clinic of some infectious diseases. Through direct or indirect ecological and functional competition, FMT may stimulate decolonization of pathogens or opportunistic pathogens, modulating immune response and colonic inflammation, and restoring intestinal homeostasis, with reduction of host damage. Herein, we discuss how diagnostic parasitology may contribute to design clinical metagenomics pipelines and FMT programs, especially in pediatric subjects. The consequences of a more specialized diagnostics in the context of gut microbiota communities may improve the clinical parasitology and extend its applications to the prevention and treatment of several communicable and even noncommunicable disorders.

Background: Nonalcoholic fatty liver disease (NAFLD) is regarded as a component of metabolic syndrome, which has insulin resistance (IR) as the primary physiopathological event. The aim of study was to establish the association between IR, assessed using triglyceride and glucose index (TyG), and histopathological features of NAFLD lesions. Methods: The study included patients with metabolic syndrome. Fasting plasma glucose (FPG), fasting lipid profiles and liver enzymes were measured. IR was assessed by TyG index. Liver biopsy was performed for assessment steatosis and fibrosis. Results: TyG index had a mean value of 8.93 ± 1.45, with a higher value in the patients with overweight (p=0.002) and obesity (p=0.004) than in the patients with normal weight. TyG index mean value of 8.78 ± 0.65 in subjects without NASH, 8.91 ± 0.57 in patients with borderline NASH and 9.13 ± 0.55 in patients with definite NASH. Significant difference was found between subjects without NASH and the ones with definite NASH (p=0.004). The analysis of the area under the ROC curve proved that TyG index is a predictor for NASH (p=0.043). Conclusion: TyG index is a facile tool used to identify individuals at risk for NAFLD, but not for the progression of liver lesions.

Introduction: There are unique technical and management challenges associated with living donor liver transplantation (LDLT) for Budd-Chiari Syndrome (BCS). The outcomes of LDLT for BCS in comparison to other indications remains unclear and warrants elucidation. Methods: Data of 24 BCS patients who underwent LDLT between January 2012 and June 2019 were analyzed. There were 20 adults and 4 children. The early and long-term outcomes of adult LDLT BCS patients were compared to a control group of LDLT patients for other indications and matched using propensity scoring methodology. Results: Primary BCS was observed in 22(91.7%) patients. Caval replacement was performed in 7(29.1%) patients. Early and late hepatic venous outflow tract (HVOT) complications were seen in 1(5.5%) and 3(16.7%) patients. Preoperative acute kidney injury was identified as a risk factor for mortality in the BCS cohort (p =0.013). On comparison, BCS recipients were younger with fewer comorbidities, more large volume ascites and higher rates of PVT. They also had longer cold ischemia time, increased blood loss and transfusion requirements, increased hospital stay, and higher late outflow complications. The 1-year and 3-year survivals were similar to non-BCS cohort (84.2% vs 94% and 70% vs 91.9%, respectively, log rank test p=0.09). Conclusion: LDLT is remains a good option for symptomatic BCS who have failed non-transplant interventions. The clinical and risk factor profile of BCS recipients is distinct from non-BCS recipients. By following an algorithmic management protocol, we show on propensity-score matched analysis that outcomes of LDLT for BCS are similar to non-BCS indications.

Background: Hepatocellular carcinoma (HCC) is a global health problem associated with chronic liver disease. The pathogenesis of chronic liver disease varies according to the underlying etiological factor, although in most cases it develops from a liver cirrhosis. The worsening progression of liver disease is accompanied by pathological angiogenesis, which is a prerequisite that favors the development of HCC. The aim of this study is to evaluate the clinical utility of circulating angiogenic markers VEGF, Ang-1, Ang-2, the Angiopoietin receptor (Tie1/2), HGF and PECAM-1 to screen early onset patients and to follow the evolution of HCC. Materials and Methods: We enrolled 62 patients; 33 out of 62 subjects were diagnosed for HCC and 29/62 for liver cirrhosis of different etiology without signs of neoplasia. Patients underwent venous blood sampling before and after treatments for VEGF, Ang-1, Ang-2, Tie1, Tie2, HGF and PECAM-1 measurement. Results: Ang-1 and Ang-2 are detectable not only in patients already suffering from HCC but also in cirrhotic patients without signs of cancer. Patients with HCC show higher HGF concentrations than patients with cirrhosis. A significant reduction in serum levels of Ang-2, Ang-2/Ang-1 and Ca 19-9 after DAAs therapy was observed. Moreover, VEGF levels were increased after treatment of HCC. Conclusion: The preliminary study here presented confirms that the mechanism of tumor angiogenesis is very complex and involves a very large number of factors. The integration of different methodologies and multi-marker algorithms is likely to emerge for the early diagnosis of HCC and the monitoring of the risk of relapse.

Wheat gluten contains epitopes that trigger celiac disease (CD). A life-long strict gluten-free diet is the only treatment accepted for CD. However, very low-gluten wheat may provide an alternative treatment to CD. Conventional plant breeding methods are not sufficient to produce celiac-safe wheat. RNA interference technology, to some extent, succeeded in the development of safer wheat varieties. However, these varieties had multiple challenges in their implementation. Clustered Regularly Interspaced Short Palindromic Repeats-associated nuclease 9 (CRISPR/Cas9) is a versatile gene-editing tool that has the ability to edit the immunogenic gluten genes. So far, only a few studies have applied CRISPR/Cas9 to modify the wheat genome. In this article, we reviewed published literature that applied CRISPR/Cas9 in wheat genome editing to investigate the current status of the CRISPR/Cas9 system to produce a low-immunogenic wheat variety. We found that in recent years, the CRISPR/Cas9 system has been continuously improved to edit the complex hexaploid wheat genome. Although some reduced immunogenic wheat varieties have been reported, CRISPR/Cas9 has still not been fully explored in editing the wheat genome. We conclude that further studies are required to apply the CRISPR/Cas9 gene-editing system efficiently for the development of celiac-safe wheat variety and to establish it as a “tool to celiac safe wheat.”

Gene expression data is key for the functional annotation of single nucleotide polymorphisms (SNPs) identified in genome-wide association studies (GWAS). Expression and splicing quantitative trait loci (e/sQTLs) in normal colon tissue, such as those from the University of Barcelona and University of Virginia RNA sequencing project (BarcUVa-Seq) and the Genotype-Tissue Expression project (GTEx), are required to gain biological insight of colon-related diseases risk loci. Moreover, transcriptome-wide association studies (TWAS) rely on reference gene expression imputation panels in the tissue of interest to nominate susceptibility genes. Also, it is of high interest to study the relationships between genes in a network framework. For facilitating these analyses, we have updated and expanded the scope of the Colon Transcriptome Explorer (CoTrEx) to the version 2.0. This web-based resource provides exhaustive visualization and analysis of transcriptome-wide gene expression profiles of normal colon tissue from BarcUVa-Seq and GTEx. In addition to the integration of new datasets, CoTrEx 2.0 provides additional e/sQTLs sets, as well as gene expression prediction models and regulatory and co-expression networks. It is freely available at https://barcuvaseq.org/cotrex/. Overall, it is of high interest for researchers aiming to investigate the genetic susceptibility to colon-related complex traits and diseases.

Ulcerative colitis (UC) is a chronic autoimmune disorder affecting the colonic mucosa. UC is a subtype of inflammatory bowel disease along with Crohn’s disease and presents with varying extraintestinal manifestations. No single etiology for UC has been found, but a combination of genetic and environmental factors is suspected. Research has focused on the role of intestinal dysbiosis in the pathogenesis of UC, including the effects of dysbiosis on the integrity of the colonic mucosal barrier, priming and regulation of the host immune system, chronic inflammation, and progression to tumorigenesis. Characterization of key microbial taxa and their implications in the pathogenesis of UC and colitis-associated cancer (CAC) may present opportunities for modulating intestinal inflammation through microbial-targeted therapies. In this review, we will discuss the microbiota-immune crosstalk in UC and CAC, as well as the evolution of microbiota-based therapies.

The human gut microbiota consists of bacteria, archaea, fungi, and viruses. It is a dynamic ecosystem shaped by several factors, which play an essential role in both healthy and diseased states of humans. A disturbance of the gut microbiota, also termed “dysbiosis,” is associated with increased host susceptibility to a range of diseases. Because of splanchnic ischaemia, exposure to antibiotics, and/or underlying the disease critically ill patients loose 90% of the commensal organisms in their gut within hours after the insult. This is followed by a rapid overgrowth of potentially pathogenic and pro-inflammatory bacteria altering metabolic, immune, and even neurocognitive functions and turning the gut into the driver of systemic inflammation and multiorgan failure. Indeed, restoring healthy microbiota by means of faecal microbiota transplantation (FMT) in the critically ill is an attractive and plausible concept in intensive care. Yet, available data from controlled studies are limited to probiotics and FMT for severe C. difficile infection or severe inflammatory bowel disease. Case series and observational trials generate hypothesis that FMT might be feasible and safe in immunocompromised patients, refractory sepsis, or severe antibiotic-associated diarrhea in ICU. There is a burning need to test these hypotheses in randomized controlled trials powered for determination of patient-centered outcomes.

Introduction: The gastrointestinal tract (GI) is the second most affected organ system in systemic sclerosis or systemic/localized scleroderma (SSc) and is an important topic for research. Approximately 90% of patients with scleroderma exhibit pathology of the GI tract. The systemic scleroderma has the potential to impact any part of the gastrointestinal tract, between the oral cavity and anorectum. The pathological complications of scleroderma adversely impact the health-related quality of life of the affected patients and increase the treatment burden of patients and medical professionals. Study Aim: We summarized the epidemiology, commonly reported clinical manifestations, complications, and available therapies for treating the GI pathology in systemic scleroderma patients. Methodology: We performed a literature review using the keywords "systemic sclerosis," "scleroderma," "GI manifestations in scleroderma," and "GI complications of scleroderma" across databases, including Google Scholar, Medline, Embase, and PubMed. We also analyzed a range of case reports concerning scleroderma manifestations and treatment modalities. Results: Our research revealed the annual incidence of SSc attributing to19.3 cases per million adults in the United States. We found the highest incidence of systemic scleroderma in patients within the age range of 44-55 years. Our results affirmed 5:1 incidence of systemic scleroderma that confirmed the higher impact of this disease condition in females than male populations. We found that the gastrointestinal manifestations of systemic scleroderma predominantly elevate the morbidity and mortality incidence among the affected patients. Esophageal and intestinal manifestations impact 90% and 40-70% of patients with systemic scleroderma. The small bowel hypomotility and small intestinal bacterial overgrowth (SIBO) in systemic scleroderma cases trigger the episodes of malabsorption and malnutrition that eventually add to 50% of the mortality rate. Systemic sclerosis is associated with the high incidence of fecal incontinence that triggers depression and its deleterious mental health manifestations in many clinical scenarios. Conclusion: The gastrointestinal complications in systemic sclerosis potentially deteriorate the daily living activities of the affected patients. The systematic management of the gastrointestinal complications of systemic scleroderma warrants multidisciplinary approaches. Prospective studies should focus on developing targeted therapies for improving the recovery patterns and prognostic outcomes in systemic scleroderma cases.

Approximately 240 million people are chronically infected with hepatitis B virus (HBV), despite four decades of an effective HBV vaccine. During chronic infection, HBV forms two distinct templates responsible for viral gene transcription: (1) episomal covalently closed circular (ccc)DNA and (2) host-genome integrated viral templates. Multiple ubiquitous and liver-specific transcription factors are recruited onto these templates and modulate viral gene transcription. This review details the latest developments in antivirals that inhibit HBV gene transcription, and their impact on the stability of viral transcripts. Notably, nuclear receptor agonists exhibit potent inhibition of viral gene transcription from cccDNA, small molecule inhibitors repress HBV X protein-mediated transcription from cccDNA and small interfering RNAs and single-stranded oligonucleotides result in transcript degradation from both cccDNA and integrant templates. These antivirals mediate their effects by reducing viral transcripts abundance, eventually leading to loss of surface antigen expression, and can potentially be added to the arsenal of drugs with demonstrable anti-HBV activity. Thus, these candidates deserve special attention for future repurposing or further development as anti-HBV therapeutics.

Colorectal cancer is a major threat to the society causing the death through metastasis to several patients with stage IV. Computational tools provide a relatively quick procedure in order to evaluate several molecules for their drug activity. Prenylated flavonoids are well known for their anticancer properties even in colon cancer. Here, we provided altered structures of chalcones, based on theoretical studies that are showing better binding affinities to several colon cancer related proteins. Using molecular docking and dynamics, alongside with density function theory and ADMET studies we are representing two new derivatives of Xanthohumol prenylated flavonoids having promising results against this disease.

Leptin is the archetypal adipokine that promotes a negative whole-body energy balance largely through its action on brain leptin receptors. As such, the sustained weight loss and food intake suppression induced by Roux-en-Y gastric bypass (RYGB) surgery have been attributed to enhancement of leptin receptor signalling. We formally revisited this idea in Zucker Fatty fa/fa rats, an established genetic model of leptin receptor deficiency, and carefully compared their body weight, food intake and oral glucose tolerance after RYGB with that of sham-operated fa/fa (obese) and sham-operated fa/+ (lean) rats. We found that RYGB rats sustainably lost body weight, which converged with that of lean rats and was 25.5 % lower than that of obese rats by the end of the 4 week study period. Correspondingly, daily food intake of RYGB rats was similar to that of lean rats from the second postoperative week, while it was always at least 33.9 % lower than that of obese rats. Further, oral glucose tolerance of RYGB rats was normalized at the forth postoperative week. These findings assert that leptin is not an essential mediator of the sustained weight loss and food intake suppression as well as the improved glycemic control induced by RYGB, and instead point to additional circulating and/or neural factors.

Dipeptidyl peptidase (DPP) 9, DPP8, DPP4 and fibroblast activation protein (FAP) are the four enzymatically active members of the S9b protease family. Associations of DPP9 with human liver cancer, exonic single nucleotide polymorphisms (SNPs) in DPP9 and loss of function (LoF) variants have not been explored. Human genomic databases including The Cancer Genome Atlas (TCGA) were interrogated to identify DPP9 LoF variants and associated cancers. Survival and gene signature analyses were performed on hepatocellular carcinoma (HCC) data. We found that DPP9 and DPP8 are intolerant to LoF variants. DPP9 LoF variants were most often associated with uterine carcinoma. Two DPP9 intronic SNPs that have been associated with lung fibrosis and COVID-19 were not associated with liver fibrosis or cancer. All four DPP4-like genes were overexpressed in liver tumours and their joint high expression was associated with poor survival in HCC. Increased DPP9 expression was associated with obesity in HCC patients.. High expression of genes that positively correlated with overexpression of DPP4, DPP8, and DPP9 were associated with very poor survival in HCC. Enriched pathways analysis of these positively correlated genes featured Toll-like receptor and SUMOylation pathways. This comprehensive data mining suggests that DPP9 is essential for human survival and the DPP4 protease family is important in cancer pathogenesis.

Non-alcoholic fatty liver disease (NAFLD) continues to rise and has become the most common cause of chronic liver disease among all ages and ethnicities. Metabolic disorders such as obesity and insulin resistance are closely associated with sarcopenia and NAFLD. Sarcopenic obesity is a clinical disorder characterized by the simultaneous loss of skeletal muscle and gain of adipose tissue. It is associated with worse outcomes in individuals with NAFLD. It is projected that NAFLD and sarcopenia will rise as the prevalence of obesity continues to increase at an unparallel rate. Recently, sarcopenia and sarcopenic obesity have gained considerable interest, but we still lack a well-defined definition and a management approach. Therefore, it is imperative to continue shining the light on this topic and better understand the underlying mechanism as well as treatment options. In this review article, we aimed to address the pathophysiology, impact, and outcomes of sarcopenic obesity on NAFLD.

Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal0 tract (GIT), including Crohn’s disease (CD) and ulcerative colitis (UC), which differ in the location and lesion extensions. Both diseases are associated with microbiota dysbiosis, with a reduced population of butyrate-producing species, abnormal inflammatory response, and micronutrient deficiency (e. g. vitamin D hypovitaminosis). Vitamin D (VitD) is involved in immune cell differentiation, gut microbiota modulation, gene transcription, and barrier integrity. Vitamin D receptor (VDR) regulates the biological actions of the active VitD (1α, 25-dihydroxyvitamin D3), and is involved in the genetic, environmental, immune, and microbial aspects of IBD. VitD deficiency is correlated with disease activity and its administration targeting a concentration of 30 ng/mL may have the potential to reduce disease activity. Moreover, VDR regulates functions of T cells and Paneth cells and modulates release of antimicrobial peptides in gut microbiota-host interactions. Meanwhile, beneficial microbial metabolites, e.g. butyrate, upregulate the VDR signaling. In this review, we summarize the clinical progress and mechanism studies on VitD /VDR related to gut microbiota modulation in IBD. We also discuss epigenetics in IBD and the probiotic regulation of VDR. Furthermore, we discuss the existing challenges and future directions. There is a lack of well-designed clinical trials exploring the appropriate dose and the influence of gender, age, ethnicity, genetics, microbiome, and metabolic disorders in IBD subtypes. To move forward, we need well-designed therapeutic studies to examine whether enhanced vitamin D will restore functions of VDR and microbiome in inhibiting chronic inflammation.

The virtually complete loss of intestinal worms, known as helminths, from Western society has resulted in elimination of a range of helminth-induced morbidities. Unfortunately, that loss has also led to inflammation-associated deficiencies in immune function, ultimately contributing to widespread pandemics of allergies, autoimmunity, and neuropsychiatric disorders. Several socio-medical studies have examined the effects of intentional reworming, or self-treatment with helminths, on a variety of inflammation-related disorders. In this study, the latest results from ongoing socio-medical studies are described. The results point toward two important factors that appear to be overlooked in some if not most clinical trials. Specifically, (a) the method of preparation of the helminth can have a profound effect on its therapeutic efficacy, and (b) variation between individuals in the effective therapeutic dosage apparently covers a 10-fold range, regardless of the helminth used. These results highlight current limits in our understanding of the biology of both hosts and helminths, and suggest that information from self-treatment may be critical in moving the field forward into mainstream medicine.

The brain reciprocally communicates with the rest of the body via neural, endocrine, immune, and other systems. This is crucial for coordinating the complex behavioral and physiological responses needed to cope with the many challenges of life. The Anterior Cingulate Cortex (ACC) is a key brain structure involved in assessing rewards and threats, as well as activating appropriate responses. This is a dynamic process that depends on evolving needs and challenges. Important challenges include illness or injury. These typically involve inflammation and pain, which evoke neuroinflammatory processes in the brain to drive sickness behaviours. In the short term, sickness behaviours are considered adaptive, as they promote convalescence (e.g. low mood; lethargy, fatigue, social withdrawal), and enhanced threat appraisal (e.g. anxiety) to combat increased risk/vulnerability associated with sickness. Chronic inflammation, however, appears to remodel the system to inappropriately activate threat-coping responses, resulting in depressive and/or anxious phenotypes. These mood disorders are particularly pronounced in diseases and disorders associated with gut dysfunction, which feature chronic inflammation and altered ACC function. We propose that chronic inflammation remodels ACC physiology such that it errantly predicts heightened danger based on a mental model (a.k.a ‘schema’) of the world. This evokes chronic activation of threat-coping systems, including endocrine signaling (e.g. adrenaline), and anxiety. Inflammation can be driven by brain systems involving ACC, leading to a feedback-cycle that self-reinforces pathological states. This theory accounts for a wealth of clinical and preclinical data that implicate the ACC in disorders of mood and gastrointestinal function, and reveals a key player in the gut-brain axis that may represent a novel therapeutic target.

Background:Although highly strict social distancing and viral spread protection guidelines are in force, the reported numbers of COVID-19 cases across the world are still increasing. This indicates that we are still unable to completely understand the transmission routes of SARS-CoV-2. One of the possible routes that can play a significant role is the fecal-oral transmission since SARS-CoV-2 can replicate in the intestines as demonstrated by isolation of infectious virus from fecal samples of COVID-19 cases. Scope and approach:In this review, we compare the characteristics of SARS-CoV-2 with the distinctive characteristics of enteric foodborne viruses. We also discuss and respond to the arguments given in some reports that downplay the importance of foodborne transmission route of SARS-CoV-2. Key findings and conclusions:Enteric viruses such as human noroviruses (HuNoVs) and hepatitis A virus (HAV) are known to transmit through foods such as fresh produce and berries, leading to frequent multistate foodborne disease outbreaks all over the world. SARS-CoV-2 was found to share four distinctive characteristics of foodborne viruses that allow them to transmit through foods. This similarity in characteristics, recent report of detecting SARS-CoV-2 particles from frozen food packages in China, and recent suspected foodborne COVID-19 case in New Zealand, indicate that foodborne transmission of SARS-CoV-2 is more evident than previously thought possible. To support or deny this route of transmission, urgent research needs to be undertaken to answer two primary questions and many secondary ones as described in this review.

Aims: Primary AIM of the study was to evaluate effect of prolonged hospital stay on Surgical site infections We also evaluated effect of prolonged hospital stay on overall morbidity in Gastrointestinal and Hepatobiliary Surgery as secondary outcome. Methods: We retrospectively analysed all the patients who underwent gastrointestinal and hepatobiliary surgery between April 2017 to March 2020. On our analysis we found mean hospital stay in patient who did not develop SSI and/or morbidity was 4 days (Total hospital stay) vs 6 days who developed morbidity (hospital stay before diagnosis of SSI or diagnosis or morbid event). Based on this to avoid selection bias, we did 1:1 propensity score analysis between patients who had 4 or less than hospital stay vs patients who had 5 or more hospital stay before diagnosis of surgical site infection and/or morbid event. We took all the preoperative and intraoperative factors like Age, sex, malignant disease, ASA score, CDC grade of surgery, open or laparoscopic surgery, HPB surgeries, colorectal surgeries, Upper Gastrointestinal surgeries and small intestinal surgeries as covariates. We used nearest neighbor matching protocol with a calipher of 0.2. Cases were not reusable after matching. Statistical analysis was done using SPSS version 23. Results: We included 348 patients operated between April 2017 and March 2020 in our analysis. After 1:1 propensity score matching 58 patients included in study arm (prevent hospital stay more than 4 days) and 56 patients in control arm. Both groups were comparable with regard to Age, Sex, Surgery for malignant disease, ASA score, CDC grade of surgery, HPB surgeries, Small intestinal surgeries, Colorectal surgeries, upper gastrointestinal surgeries, intraoperative blood product requirement, intraoperative hypotension or any other event, operative time. Prolonged hospital stay (> 4 days) was significantly associated with surgical site infections (p<0.0001), morbidity (p=0.001). Open surgeries were associated with prolonged hospital stay. (p=0.032). Conclusion: Prolonged Hospital stay is associated with increase surgical site infection and morbidity in Gastrointestinal and Hepatobiliary Surgery.

Understanding the importance of gut microbiota (GM) in non-alcoholic fatty liver disease (NAFLD) has raised the hope for therapeutic microbes. We have shown that high hepatic fat associated with low abundance of Faecalibacterium prausnitzii in humans and further, administration of F. prausnitzii prevented NAFLD in mice. Here, we aimed to target F. prausnitzii by prebiotic xylo-oligosaccharides (XOS) to treat NAFLD. First, the effect of XOS on F. prausnitzii growth was assessed in vitro. Then, XOS was supplemented or not with high (HFD) or low (LFD) fat-diet for 12-weeks in Wistar rats (n=10/group). XOS increased F. prausnitzii growth having only minor impact on the GM composition. When supplemented with HFD, XOS prevented hepatic steatosis. The underlying mechanisms involved enhanced hepatic β-oxidation and mitochondrial respiration. 1H-NMR analysis of caecal metabolites showed that compared to HFD, LFD group had healthier caecal short-chain fatty acid profile and the combination of HFD and XOS was associated with reduced caecal isovalerate and tyrosine, metabolites previously linked to NAFLD. Caecal branched-chain fatty acids associated positively and butyrate negatively with hepatic triglycerides. In conclusion, our study identifies F. prausnitzii as a possible target to treat NAFLD with XOS. The underlying preventive mechanisms involved improved hepatic oxidative metabolism.

Aims and objectives: The primary aim of our study was to evaluate morbidity and mortality following feeding jejunostomy in pancreaticoduodenectomy compared to the control group. We also evaluated individual complications like delayed gastric emptying; post operative pancreatic fistula, superficial and deep surgical site infection. Material and Methods: The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and MOOSE guidelines. Heterogeneity was measured using Q tests and I2.the random-effects model was used. Results: Four studies including Total of 1639 patients were included in the analysis. Total 843 patients were included in Feeding jejunostomy group and 796 patients included in control group without feeding jejunostomy. Over all morbidity was significantly higher in feeding jejunostomy group. (P = 0.001). There was no significant difference between both the groups. (P=0.07). Delayed gastric emptying was significantly higher in feeding jejunostomy group. [P=0.021]. There was no significant difference in development of pancreatic fistula between the two groups. Deep surgical site infection was significantly higher in feeding jejunostomy group. (P=0.013). Hospital stay was significantly more in feeding jejunostomy group (p<0.0001). There was no significant difference between readmission; TPN requirement and time to start oral feed. Conclusion: Feeding jejunostomy seems to be associated with increased morbidity and increased length of stay.

Necroptosis is a caspases-independent form of programmed cell death exhibiting intermediate features between necrosis and apoptosis. Albeit some physiological roles during embryonic development, tissue homeostasis and innate immune response are documented, necroptosis is mainly considered a pro-inflammatory cell death. Key actors of necroptosis are the receptor-interacting-protein-kinases, RIPK1 and RIPK3, and their target, the mixed-lineage-kinase-domain-like protein, MLKL. The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. Altered necroptosis at the intestinal epithelium leads to uncontrolled microbial translocation and deleterious inflammation. Indeed, necroptosis has been associated to chronic inflammatory diseases and cancer. Drugs that inhibit necroptosis could, therefore, be used therapeutically for the treatment of these diseases, and researches to develop such inhibitors are already underway. In this Review, we outline pathways for necroptosis and its role in chronic inflammation and cancer. We also discuss current and developing therapies that target necroptosis machinery.

Ulcerative colitis (UC) is a common chronic disease of the large intestine. Current anti-inflammatory drugs prescribed to treat this disease have limited utility due to significant side-effects. Thus, immunotherapies for UC treatment are still sought. In the DSS mouse model of UC, we recently demonstrated that systemic administration of the Bin1 monoclonal antibody 99D (Bin1 mAb) developed in our laboratory was sufficient to reinforce intestinal barrier function and preserve an intact colonic mucosa, compared to control subjects which displayed severe mucosal lesions, high-level neutrophil and lymphocyte infiltration of mucosal and submucosal areas, and loss of crypts. Here we report effects of Bin1 mAb on colonic neurons and the gut microbiome that correlate with the benefits of treatment. In the DSS model, we found that induction of UC was associated with disintegration of enteric neurons and elevated levels of glial cells, which translocated to the muscularis at distinct sites. Further, we characterized an altered gut microbiome in DSS treated mice associated with pathogenic proinflammatory characters. Both of these features of UC induction were normalized by Bin1 mAb treatment. With regard to microbiome changes, we observed in particular that Firmicutes were eliminated by UC induction and that Bin1 mAb treatment restored this phylum including the genus Lactobacillus and Akkermansia as beneficial microorganisms. Overall, our findings suggest that the intestinal barrier function restored by Bin1 immunotherapy in the DSS model of UC is associated with a preservation of enteric neurons and an improvement in the gut microbiome, contributing overall to a healthy intestinal tract.

In recent years, the consumption of over-the-counter probiotics used to promote health has grown rapidly worldwide and become an industry. In medicine, various studies have proven that probiotics can help improve the immune system and intestinal health. They are usually safe, but in some rare cases, they may cause concerning adverse reactions. Although the use of probiotics has been widely popularized in the public, the results of many probiotics clinical trials are contradictory. Especially for the cancer patients, the feasibility of probiotics management to provide benefits by targeting cancer and lessening anti-cancer side effects requires further investigations. And this review summarizes the interactions between probiotics and the host and current pros and cons of applying probiotics in the cancer patients.

To analyze the effects of CYP3A5 polymorphism on liver function after LT and to characterize the pharmacokinetics of tacrolimus after conversion from a twice-daily regimen to a once-daily extended-release formulation. A prospective open-label study included 60 stable liver transplant recipients who underwent 1:1 conversion from twice-daily tacrolimus to once-daily tacrolimus. All participants were genotyped for CYP3A5 polymorphism. The study was registered at ClinicalTrials.gov (NCT 02882113). Twenty-eight patients were enrolled in the CYP3A5 expressor group and 32 in the non-expressor group. Although there was no statistical difference, incidence of liver dysfunction was higher in the expressor group than in the non-expressor group when converted to once-daily extended-release tacrolimus (P=0.088). No biopsy-proven acute rejection, graft failure, and mortality were observed in either group. The decrease in dose-adjusted trough level (- 42.9% vs. - 26.1%) and dose/kg-adjusted trough level of tacrolimus (- 40.0% vs. - 23.7%) was significantly greater in the expressor group than in the non-expressors after the conversion. The absorption of the tacrolimus in the non-expressor group was slower than in the expressors. In line with this observation, the AUC for once-daily tacrolimus correlated with Cmin in the non-expressors and Cmax in the expressors. Determination of CYP3A5 genotype in liver transplant recipients might be helpful in prediction of tacrolimus pharmacokinetics after conversion from a twice-daily regimen to a once-daily formulation.