Hui Jason M, Sud Archana, Farrell Geoffrey C, Bandara Priyanka, Byth Karen, Kench James G, McCaughan Geoffrey W, George Jacob
Storr Liver Unit, Westmead Millennium Insitute, and Department of Gastroenterology and Hepatology, University of Sydney at Westmead Hospital, New South Wales, Australia.
Gastroenterology. 2003 Dec;125(6):1695-704. doi: 10.1053/j.gastro.2003.08.032.
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.
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.
Hepatitis C virus-infected subjects with stage 0 or 1 hepatic fibrosis had higher levels of insulin, C peptide, and HOMA-IR (all P < or = 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).
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.
慢性丙型肝炎病毒感染与2型糖尿病患病率增加相关。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中纤维化形成的一种机制。
在260例丙型肝炎病毒感染患者中，我们研究了组织学结果与人体测量学及生化数据之间的关系，包括通过稳态模型评估（HOMA-IR）确定的胰岛素抵抗。我们还比较了121例肝纤维化0或1期的丙型肝炎病毒患者亚组与137名按性别、体重指数和腰臀比匹配的健康志愿者之间的空腹血清胰岛素、C肽和HOMA-IR水平。
与匹配的健康对照相比，肝纤维化0或1期的丙型肝炎病毒感染患者的胰岛素、C肽和HOMA-IR水平更高（均P≤0.01）。在250例丙型肝炎病毒患者（纤维化分期0至4期）中，病毒基因型以及门静脉而非小叶炎症是HOMA-IR的单变量预测因素。通过多元线性回归分析，HOMA-IR的独立预测因素包括体重指数（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）和基因型3状态（P = 0.01）。基因型3的HOMA-IR显著低于其他基因型（在调整其余独立预测因素的影响后具有可比性）。HOMA-IR是纤维化程度（P<0.001）和纤维化进展速率（P = 0.03）的独立预测因素。
丙型肝炎病毒可能无论肝病严重程度如何都诱导胰岛素抵抗，且这种效应似乎具有基因型特异性。此外，我们的研究结果支持胰岛素抵抗可能促成慢性丙型肝炎病毒感染中纤维化进展这一假说。
