REVIEW | doi:10.20944/preprints202008.0417.v1
Subject: Life Sciences, Endocrinology & Metabolomics Keywords: hepatic fibrosis; hepatocullar carcinoma; vibration controlled transient elastography
Online: 19 August 2020 (13:00:28 CEST)
The prevalence of obesity or metabolic syndrome is increasing worldwide (“Globally metabodemic”). Approximately 25% of adult general population is suffering from nonalcoholic fatty liver disease (NAFLD) which has become serious health problem. Hepatic fibrosis is the most significant determinant of all cause and liver -related mortality in NAFLD. Noninvasive test (NIT) should be urgently required to evaluate hepatic fibrosis in NAFLD. Fibrosis-4 (FIB-4) index is the 1st triaging tool for excluding advanced fibrosis because of its accuracy, simplicity, and cheapness especially for general physicians or endocrinologists, although FIB-4 index has several drawbacks. Accumulating evidence has suggested that vibration controlled transient elastography (VCTE) and the enhanced liver fibrosis (ELF) test may become useful as the 2nd step after triaging by FIB-4 index. The leading cause of mortality in NAFLD is cardiovascular disease (CVD), extrahepatic malignancy, and liver-related diseases. NAFLD often complicates chronic kidney disease (CKD), resulting in increased simultaneous liver kidney transplantation (SLKT). FIB-4 index could be a predictor of not only liver-related mortality and incident hepatocullar carcinoma (HCC) but also prevalent and incident CKD, CVD, and extrahepatic malignancy. Although NITs as milestones for evaluating treatment efficacy have never been established, FIB- 4 index is expected to reflect histological hepatic fibrosis after treatment in several longitudinal studies. We here review the role of FIB-4 index as 1st step NIT in management of NAFLD.
REVIEW | doi:10.20944/preprints202001.0171.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: Dipeptidyl peptidase-4; Fibroblast growth factor; Gastrointestinal peptide; Glucagon-like peptide 1; Glucagon receptor; Peroxisome proliferator-activated receptor; Sodium glucose cotransporter
Online: 16 January 2020 (11:44:49 CET)
Liver related diseases are the 3rd leading causes (9.3%) of mortality in type 2 diabetes mellitus (T2DM) in Japan. T2DM is closely associated with nonalcoholic fatty liver disease (NAFLD) which is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma (HCC) and hepatic failure. There are no established pharmacotherapies for NASH patients with T2DM. Though vitamin E is established as a 1st line agent in NASH without T2DM, its efficacy was recently denied in NASH with T2DM. The effects of pioglitazone on NASH histology with T2DM have extensively been established, but several concerns exist such as body weight gain, fluid retention, cancer incidence, and bone fracture. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium/glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH (LEAN study, LEAD trial, and E-LIFT study). Among a variety of SGLT2 inhibitors, dapagliflozin have already entered phase 3 trials (DEAN study). A key clinical question is what kinds of anti-diabetic drugs are the most appropriate for the treatment of NASH to prevent progression of hepatic fibrosis resulting in HCC/liver-related mortality without increasing risk at cardiovascular or renal events. The combination therapies such as glucagon receptor agonist/GLP-1 or gastrointestinal peptide /GLP-1 will be under development. This review focuses on antidiabetic agents and future perspectives on the view of the treatment of NAFLD with T2DM.
REVIEW | doi:10.20944/preprints202007.0314.v1
Subject: Life Sciences, Endocrinology & Metabolomics Keywords: hepatic fibrosis; Mac-2 binding protein glycated isomer; apoptosis inhibitor of macrophage; patatin-like phospholipase domain-containing protein 3; α-fetoprotein; PIVKA-II
Online: 14 July 2020 (13:55:16 CEST)
Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of hepatocellular carcinoma (HCC), liver-related mortality, and liver transplantation. There is reasonable epidemiological cohort data to recommend surveillance of patients with NAFLD based upon the incidence of HCC. The American Gastroenterology Association (AGA) expert review published in 2020 recommend that NAFLD patients with cirrhosis or advanced fibrosis estimated by non-invasive tests (NITs) should consider HCC surveillance. NITs include fibrosis-4 (FIB-4) index, the enhanced liver fibrosis (ELF) test, FibroScan, and MR elastography. The recommended surveillance modality is abdominal ultrasound (US) given that it is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with NAFLD. In NAFLD patients with a high likelihood of having an inadequate US or if US is attempted but inadequate, CT or MRI may be utilized. The GALAD score, consisting of age, gender, AFP, lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II), can help to identify high risk of incident HCC in NAFLD patients. Innovative parameters including Mac-2 binding protein glycated isomer , type IV collagen 7S, free apoptosis inhibitor of macrophage, combination of single nucleoside polymorphisms are expected to be established. Considering a large number of NAFLD population, optimal screening tests must meet several criteria including high sensitivity, cost effectiveness and availability.