Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC.
Intervirology. 2013;56(3):166-71. doi: 10.1159/000343913. Epub 2013 Feb 8.
BACKGROUND/AIMS: Hepatitis C virus (HCV) core protein can induce liver steatosis and glucose intolerance in transgenic mice. We aimed to clarify the association of HCV core region heterogeneity with the development of insulin resistance (IR) among patients with chronic hepatitis C (CHC).
A total of 56 non-diabetic CHC genotype-1b patients were enrolled. IR was evaluated by the homeostasis model assessment (HOMA). The amino acid (aa) sequences in the core region were determined by polymerase chain reaction and direct sequencing.
Patients with a higher HOMA-IR (≥3.5) had a higher ratio of aa substitutions in core 70 (p = 0.025), a higher body mass index (p = 0.021) and serum total cholesterol level (p = 0.044) and presence of hepatic steatosis (≥5%) as compared with those with a lower HOMA-IR (<3.5). Multivariate analysis showed that independent factors of higher HOMA-IR were mutated aa70 (odds ratio 3.80, p = 0.033) and body mass index (odds ratio 1.20, p = 0.042). Patients with mutated aa70 had a higher serum tumor necrosis factor-α level than those with wild-type (p = 0.014).
Substitution of the HCV-1b core region at position 70 was an independent factor associated with developing IR among patients with CHC.
背景/目的：丙型肝炎病毒（HCV）核心蛋白可诱导转基因小鼠肝脂肪变性和葡萄糖耐量异常。我们旨在阐明 HCV 核心区异质性与慢性丙型肝炎（CHC）患者胰岛素抵抗（IR）发展之间的关系。
共纳入 56 例非糖尿病 CHC 基因 1b 型患者。通过稳态模型评估（HOMA）评估 IR。通过聚合酶链反应和直接测序确定核心区的氨基酸（aa）序列。
HOMA-IR（≥3.5）较高的患者核心 70 处 aa 取代的比例较高（p = 0.025），体重指数（p = 0.021）和血清总胆固醇水平（p = 0.044）较高，且存在肝脂肪变性（≥5%）高于 HOMA-IR（<3.5）较低的患者。多因素分析显示，较高 HOMA-IR 的独立因素为突变 aa70（比值比 3.80，p = 0.033）和体重指数（比值比 1.20，p = 0.042）。突变 aa70 的患者血清肿瘤坏死因子-α水平高于野生型（p = 0.014）。
HCV-1b 核心区 70 位的取代是 CHC 患者发生 IR 的独立相关因素。
