Insulin resistance is associated with chronic hepatitis C and virus infection fibrosis progression
Insulin resistance is associated with chronic hepatitis C and virus infection fibrosis progression
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DOI：
10.1053/j.gastro.2003.08.032
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发表时间：
2003-12-01
期刊：
影响因子：
29.4
通讯作者：
George, J
中科院分区：
文献类型：
--
作者：
Hui, JM;Sud, A;George, J
背景与目的：慢性丙型肝炎病毒感染与2型糖尿病患病率增加有关。我们推测病毒诱导的胰岛素抵抗可能是慢性丙型肝炎病毒感染的纤维化机制。方法.在260例丙型肝炎病毒感染者中，我们研究了组织学结果与人体测量和生化数据之间的关系，包括由稳态模型评估（HOMA-IR）确定的胰岛素抵抗。我们还比较了121例0期或1期丙型肝炎病毒肝纤维化患者和137例健康志愿者的空腹血清胰岛素、C肽和HOMA-IR水平，这些志愿者按性别、体重指数和腰臀比匹配。结果如下：与匹配的健康对照组相比，丙型肝炎病毒感染的0期或1期肝纤维化受试者的胰岛素、C肽和HOMA-IR水平较高（P均小于或等于0.01）。在250名丙型肝炎患者中，肝纤维化0 ~ 4期、病毒基因型、门静脉炎症是HOMA-IR的单因素预测因子，而肝小叶炎症则不是，多元线性回归分析显示，HOMA-IR的独立预测因子包括体重指数（P < 0.001）、既往抗病毒治疗失败（P < 0.001）、门静脉炎症分级（P < 0.001）和基因3型状态（P = 0.01）。基因型3的HOMA-IR显著低于其他基因型（当调整其余独立预测因子的影响时，两者相当）。HOMA-IR是纤维化程度（P < 0.001）和纤维化进展率（P = 0.03）的独立预测因子。结论：丙型肝炎病毒可诱导胰岛素抵抗，无论肝脏疾病的严重程度如何，这种影响似乎是基因型特异性的。此外，我们的研究结果支持胰岛素抵抗可能导致慢性丙型肝炎病毒感染的纤维化进展的假设。
Background & Aims: Chronic hepatitis C virus infection is associated with an increased prevalence of type 2 diabetes. We hypothesized that virus-induced insulin resistance may be a mechanism for fibrogenesis in chronic hepatitis C virus infection. Methods. In 260 hepatitis C virus-infected subjects, we examined the relationship between histological findings and anthropometric and biochemical data, including insulin resistance determined by the homeostasis model assessment (HOMA-IR). We also compared fasting serum insulin, C peptide, and HOMA-IR levels between the subset of 121 hepatitis C virus patients with stage 0 or 1 hepatic fibrosis and 137 healthy volunteers matched by sex, body mass index, and waist-hip ratio. Results: Hepatitis C virus-infected subjects with stage 0 or 1 hepatic fibrosis had higher levels of insulin, C peptide, and HOMA-IR (all P less than or equal to 0.01) compared with matched healthy controls. In the 250 hepatitis C virus patients (fibrosis stage 0 to 4), viral genotype and portal, but not lobular, inflammation were univariate predictors of HOMA-IR. By multiple linear regression analysis, independent predictors of HOMA-IR included body mass index (P < 0.001), previous failed antiviral treatment (P < 0.001), portal inflammatory grade (P < 0.001), and genotype 3 status (P = 0.01). Genotype 3 had significantly lower HOMA-IR than other genotypes (which were comparable when adjusted for effects of the remaining independent predictors). HOMA-IR was an independent predictor for the degree of fibrosis (P < 0.001) and the rate of fibrosis progression (P = 0.03). Conclusions: Hepatitis C virus may induce insulin resistance irrespective of the severity of liver disease, and this effect seems to be genotype specific. Further, our findings support the hypothesis that insulin resistance may contribute to fibrotic progression in chronic hepatitis C virus infection.