Preprint Article Version 1 This version is not peer-reviewed

MERTK rs4374383 Polymorphism Predicts Progression of Liver Fibrosis in HCV-Infected Patients: A Longitudinal Study

Version 1 : Received: 19 October 2018 / Approved: 19 October 2018 / Online: 19 October 2018 (10:56:19 CEST)

A peer-reviewed article of this Preprint also exists.

Jiménez-Sousa, M.Á.; Gómez-Moreno, A.Z.; Pineda-Tenor, D.; Brochado-Kith, O.; Sánchez-Ruano, J.J.; Artaza-Varasa, T.; Gómez-Sanz, A.; Fernández-Rodríguez, A.; Resino, S. The Myeloid-Epithelial-Reproductive Tyrosine Kinase (MERTK) rs4374383 Polymorphism Predicts Progression of Liver Fibrosis in Hepatitis C Virus-Infected Patients: A Longitudinal Study. J. Clin. Med. 2018, 7, 473. Jiménez-Sousa, M.Á.; Gómez-Moreno, A.Z.; Pineda-Tenor, D.; Brochado-Kith, O.; Sánchez-Ruano, J.J.; Artaza-Varasa, T.; Gómez-Sanz, A.; Fernández-Rodríguez, A.; Resino, S. The Myeloid-Epithelial-Reproductive Tyrosine Kinase (MERTK) rs4374383 Polymorphism Predicts Progression of Liver Fibrosis in Hepatitis C Virus-Infected Patients: A Longitudinal Study. J. Clin. Med. 2018, 7, 473.

Journal reference: J. Clin. Med. 2018, 7, 473
DOI: 10.3390/jcm7120473

Abstract

Background: The myeloid-epithelial-reproductive tyrosine kinase (MERTK) is involved in hepatic steatosis, inflammation and liver fibrosis. Here we evaluated the association between the MERTK rs4374383 single nucleotide polymorphism (SNP) and liver fibrosis progression in hepatitis C virus (HCV)-infected patients. Methods: We performed a retrospective study (repeated measures design) in 208 patients who had liver stiffness measurement (LSM), which was assessed by transient elastography No patient had cirrhosis at baseline (LSM≥12.5 kPa). Results: At baseline, 53.8% were male, the median age was 47.1 years, 13.5% reported a high intake of alcohol, 10.1% were prior injection drug users, 85.3% were infected by HCV genotype 1, and 22.6% had previously failed antiviral therapy (pegylated-interferon-alpha/ribavirin). During a median follow-up of 46.6 months, 26 patients developed cirrhosis. The rs4374383 G carriers had a higher risk of increasing LSM (adjusted arithmetic mean ratio (aAMR)=1.14; p=0.006) and a higher likelihood of having an increase in LSM greater than 5 kPa (ΔLSM≥5 kPa) [adjusted odds ratio (aOR)=2.37; p=0.029], and greater than 7 kPa (ΔLSM≥7 kPa) [aOR=3.24; p=0.032], after controlling for confounding. The SNP’s association with cirrhosis progression was close to statistical significance (aOR=2.18; p=0.070). Conclusions: MERTK rs4374383 A carriers had a lower risk of liver fibrosis progression than G carriers, supporting the hypothesis that this SNP seems to have a critical role in the pathogenesis of liver disease in HCV-infected patients.

Subject Areas

liver stiffness; MERTK; chronic hepatitis C; cirrhosis; SNPs

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