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 using 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 with 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.
Highlights
Chronic hepatitis C (CHC) leads to the development of hepatic fibrosis, cirrhosis, and end-stage liver disease [1], but its natural evolution is highly variable among hepatitis C virus (HCV)-infected patients since cirrhotic patients have a shorter survival time than those without cirrhosis [1].cirrhotic patients need specific and regular follow-ups with screening for hepatocellular carcinoma and esophageal varices [1]
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 with HCV genotype 1, and 22.6% had previously failed antiviral therapy
We found a significant association between the myeloid-epithelial-reproductive tyrosine kinase (MERTK) rs4374383 single nucleotide polymorphism (SNP) and the LSM2/LSM1 ratio under dominant (AG/GG vs. AA) (aAMR = 1.28; p = 0.007) and recessive (GG vs. AA/AG) (aAMR = 1.13; p = 0.050) models of inheritance
Summary
Chronic hepatitis C (CHC) leads to the development of hepatic fibrosis, cirrhosis, and end-stage liver disease [1], but its natural evolution is highly variable among hepatitis C virus (HCV)-infected patients since cirrhotic patients have a shorter survival time than those without cirrhosis [1].cirrhotic patients need specific and regular follow-ups with screening for hepatocellular carcinoma and esophageal varices [1]. The hepatic biopsy is the gold standard test to evaluate the severity of liver disease. Given the drawbacks of liver biopsies, non-invasive tests for staging liver fibrosis have been developed during the last two decades, the evaluation of liver stiffness measurement (LSM) using transient elastography, which can accurately predict the presence of liver fibrosis/cirrhosis in CHC patients [4,5]. We evaluated the association between the MERTK rs4374383 single nucleotide polymorphism (SNP) and liver fibrosis progression in hepatitis C virus (HCV)-infected patients. 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
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