Dataset Information

The Myeloid-Epithelial-Reproductive Tyrosine Kinase (MERTK) rs4374383 Polymorphism Predicts Progression of Liver Fibrosis in Hepatitis C Virus-Infected Patients: A Longitudinal Study.

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 (?LSM ? 5 kPa) (adjusted odds ratio (aOR) = 2.37; p = 0.029), and greater than 7 kPa (?LSM ? 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.

SUBMITTER: Jimenez-Sousa MA

PROVIDER: S-EPMC6306820 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Myeloid-Epithelial-Reproductive Tyrosine Kinase (MERTK) rs4374383 Polymorphism Predicts Progression of Liver Fibrosis in Hepatitis C Virus-Infected Patients: A Longitudinal Study.

Jiménez-Sousa María Ángeles MÁ Gómez-Moreno Ana Zaida AZ Pineda-Tenor Daniel D Brochado-Kith Oscar O Sánchez-Ruano Juan José JJ Artaza-Varasa Tomas T Gómez-Sanz Alicia A Fernández-Rodríguez Amanda A Resino Salvador S

Journal of clinical medicine 20181123 12

<h4>Background</h4>The myeloid-epithelial-reproductive tyrosine kinase (MERTK) is involved in hepatic steatosis, inflammation, and liver fibrosis. Here we evaluated the association between the <i>MERTK</i> rs4374383 single nucleotide polymorphism (SNP) and liver fibrosis progression in hepatitis C virus (HCV)-infected patients.<h4>Methods</h4>We performed a retrospective study (repeated measures design) in 208 patients who had liver stiffness measurement (LSM), which was assessed using transient ...[more]

PMID: 30477195

Similar Datasets

Project description:IntroductionChronic hepatitis C is the main cause of death in patients with end-stage liver disease. Prognosis depends on the increase of fibrosis, whose progression is twice as rapid in men as in women. Aim of the study was to evaluate the effects of reproductive stage on fibrosis severity in women and to compare these findings with age-matched men.Materials and methodsA retrospective study of 710 consecutive patients with biopsy-proven chronic hepatitis C was conducted, using data from a clinical database of two tertiary Italian care centers. Four age-matched groups of men served as controls. Data about demographics, biochemistry, liver biopsy and ultrasonography were analyzed. Contributing factors were assessed by multivariate logistic regression analysis.ResultsLiver fibrosis was more advanced in the early menopausal than in the fully reproductive (P<0.0001) or premenopausal (P = 0.042) group. Late menopausal women had higher liver fibrosis compared with the other groups (fully reproductive, P<0.0001; premenopausal, P = <0.0001; early menopausal, P = 0.052). Multivariate analyses showed that male sex was independently associated with more severe fibrosis in the groups corresponding to premenopausal (P = 0.048) and early menopausal (P = 0.004) but not late menopausal pairs. In women, estradiol/testosterone ratio decreased markedly in early (vs. reproductive age: P = 0.002 and vs. premenopausal: P<0.0001) and late menopause (vs. reproductive age: P = 0.001; vs. premenopausal: P<0.0001). In men age-matched with menopausal women, estradiol/testosterone ratio instead increased (reproductive age group vs. early: P = 0.002 and vs. late M: P = 0.001).ConclusionsThe severity of fibrosis in women worsens in parallel with increasing estrogen deprivation and estradiol/testosterone ratio decrease. Our data provide evidence why fibrosis progression is discontinuous in women and more linear and severe in men, in whom aging-associated estradiol/testosterone ratio increase occurs too late to noticeably influence the inflammatory process leading to fibrosis.

Dataset Information

The Myeloid-Epithelial-Reproductive Tyrosine Kinase (MERTK) rs4374383 Polymorphism Predicts Progression of Liver Fibrosis in Hepatitis C Virus-Infected Patients: A Longitudinal Study.

Publications

The Myeloid-Epithelial-Reproductive Tyrosine Kinase (MERTK) rs4374383 Polymorphism Predicts Progression of Liver Fibrosis in Hepatitis C Virus-Infected Patients: A Longitudinal Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets