Service d'Hépatologie and INSERM UMRS 938, Hôpital Saint Antoine, Université Pierre&Marie Curie, Paris, France.
Gut. 2012 Oct;61(10):1473-80. doi: 10.1136/gutjnl-2011-300749. Epub 2012 Mar 2.
Insulin resistance is a predictor of poor response to peginterferon/ribavirin in patients infected with the chronic hepatitis C virus (HCV). There are no data on direct-acting antivirals. This exploratory analysis assessed the effect of metabolic factors and insulin resistance, measured by homoeostatic model assessment (HOMA), on virological response to telaprevir in Study C208.
Overall, 161 HCV genotype 1-infected, treatment-naïve patients received 12 weeks of telaprevir plus peginterferon/ribavirin, then 12/36 weeks of peginterferon/ribavirin depending on on-treatment response criteria. The prognostic significance of several factors, including HOMA-insulin resistance (HOMA-IR), on virological response at weeks 4 and 12, end of treatment and 24 weeks after treatment was explored by multiple regression analysis.
Baseline HOMA-IR data were available for 147 patients; baseline characteristics were consistent with the overall population. Baseline HOMA-IR <2, 2-4 and >4 was seen in 54%, 30% and 16% of patients, respectively. Neither response rates (any time point) nor week 4 viral load decline were significantly influenced by baseline HOMA-IR. In multivariate analyses, fibrosis stage and low-density lipoprotein cholesterol level were predictive of sustained virological response (OR 0.47 and 1.02, respectively). After the end of treatment, HOMA-IR was significantly lower in patients with sustained virological response than in those without (0.61 vs 1.34 for relapsers and 1.15 for non-responders; p<0.05).
In this study, baseline HOMA-IR was not predictive of virological response to telaprevir in HCV genotype 1-infected, treatment-naïve patients, while sustained virological response was associated with improved HOMA-IR. These results suggest that metabolic factors and insulin resistance do not have a significant effect on telaprevir-based treatment efficacy.
胰岛素抵抗是慢性丙型肝炎病毒（HCV）感染患者对聚乙二醇干扰素/利巴韦林应答不佳的预测因子。目前尚无直接作用抗病毒药物的相关数据。本探索性分析评估了代谢因素和胰岛素抵抗（通过稳态模型评估[HOMA]测量）对 C208 研究中替拉瑞韦治疗的病毒学应答的影响。
总共 161 例 HCV 基因型 1 感染、初治患者接受 12 周替拉瑞韦联合聚乙二醇干扰素/利巴韦林治疗，然后根据治疗期间应答标准接受 12/36 周聚乙二醇干扰素/利巴韦林治疗。通过多元回归分析探讨了包括 HOMA-胰岛素抵抗（HOMA-IR）在内的多种因素对第 4 周和第 12 周、治疗结束时以及治疗结束后 24 周的病毒学应答的预后意义。
147 例患者可获得基线 HOMA-IR 数据；基线特征与总体人群一致。基线 HOMA-IR<2、2-4 和>4 分别见于 54%、30%和 16%的患者。无论任何时间点的应答率还是第 4 周病毒载量下降，基线 HOMA-IR 均无显著影响。在多变量分析中，纤维化分期和低密度脂蛋白胆固醇水平是持续病毒学应答的预测因子（OR 分别为 0.47 和 1.02）。治疗结束后，持续病毒学应答患者的 HOMA-IR 显著低于无应答患者（复发者为 0.61 比 1.34，无应答者为 1.15；p<0.05）。
在这项研究中，基线 HOMA-IR 不能预测 HCV 基因型 1 感染、初治患者对替拉瑞韦的病毒学应答，而持续病毒学应答与 HOMA-IR 的改善相关。这些结果表明，代谢因素和胰岛素抵抗对基于替拉瑞韦的治疗效果没有显著影响。
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