背景:骨髓-上皮-生殖酪氨酸激酶(MERTK)与肝脂肪变性有关,炎症,和肝纤维化。在这里,我们评估了MERTKrs4374383单核苷酸多态性(SNP)与丙型肝炎病毒(HCV)感染患者肝纤维化进展之间的关联。
方法:我们对208例有肝脏硬度测量(LSM)的患者进行了回顾性研究(重复测量设计),使用瞬时弹性成像进行评估。没有患者在基线时出现肝硬化(LSM≥12.5kPa)。
结果:在基线时,53.8%为男性,中位年龄为47.1岁,13.5%的人报告酒精摄入量高,10.1%是注射吸毒者,85.3%的人感染了HCV基因型1,而22.6%的人先前抗病毒治疗失败(聚乙二醇化干扰素-α/利巴韦林)。在46.6个月的中位随访中,26例患者发展为肝硬化。rs4374383G携带者LSM增加的风险较高(调整后的算术平均比率(aAMR)=1.14;p=0.006),LSM增加大于5kPa(ΔLSM≥5kPa)的可能性较高(调整后的比值比(aOR)=2.37;p=0.029),且大于7kPa(ΔLSM≥7kPa)(aOR=3.24;p=0.032),在控制了混淆之后。SNP与肝硬化进展的相关性接近统计学意义(aOR=2.18;p=0.070)。
结论:MERTKrs4374383A携带者的肝纤维化进展风险低于G携带者,支持该SNP似乎在HCV感染患者的肝病发病机制中起关键作用的假设。
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.