摘要目的 研究在聚乙二醇干扰素联合利巴韦林治疗基础上加用二甲双胍对胰岛素抵抗的基因1型慢性丙型肝炎患者抗病毒疗效的影响.方法 胰岛素抵抗的基因1型慢性丙型肝炎患者98例,随机分为治疗组和对照组.对照组给予聚乙二醇干扰素α-2a联合利巴韦林治疗,治疗组在对照组的基础上加用二甲双胍.比较两组患者病毒学应答率、胰岛素抵抗稳态评估模型指数(HOMA-IR)及不良反应发生率.应用多元逻辑回归分析影响患者获得持续性病毒学应答(SVR)的因素.结果 治疗组和对照组各49例患者中,获得SVR各有29例和19例,SVR率为59.2％和38.8％(x2 =4.083,P=0.043).治疗12、24、48周,随访24周时治疗组HOMA-IR指数分别为3.00±0.65、1.90±0.45、1.75±0.40和1.60±0.35;明显低于对照组的3.50±0.72、2.90±0.64、2.74±0.48和2.60±0.55(t分别为3.610、8.947、11.091、10.738,均P＜0.01).治疗组腹泻的发生率明显高于对照组(28.6％比10.2％；x2=5.288,P=0.021).在多因素分析中,二甲双胍治疗(P=0.009)和治疗24周时HOMA-IR指数＜2(P=0.011)是预测患者获得SVR的独立因素.结论 聚乙二醇干扰素、利巴韦林和二甲双胍联合治疗安全,能增加胰岛素的敏感性,提高胰岛素抵抗的基因1型慢性丙型肝炎患者的SVR率.

abstractsObjective To investigate the effect of adding metformin to peginterferon alfa-2a and ribavirin on the efficacy in patients with genotype 1 chronic hepatitis C and insulin resistance.Methods Ninety-eight patients with genotype 1 chronic hepatitis C and insulin resistance were randomized into the treatment group (n=49) and the control group (n=49).The patients in the control group were treated with peginterferon alfa-2a and ribavirin,and those in the treatment group were treated with metformin in addition to peginterferon alfa-2a and ribavirin. The virologic response rate,the homeostasis model assessment for insulin resistence index (HOMA-IR) and incidence of side effects were compared between two groups.The related factors of sustained virological response (SVR) were studied by multivariate logistic regression analysis.Results The SVR rate of the patients in the treatment group was significantly higher than that of the control group (59.2％ vs 38.8％; x2 =4.083,P=0.043).The HOMA-IR of patients in the treatment group at week 12,24,48 of treatment and week 24 of follow-up were 3.00±0.65,1.90±0.45,1.75±0.40 and 1.60±0.35,respectively,which were all lower than those in the control group (3.50±0.72,2.90±0.64,2.74± 0.48 and 2.60±0.55,respectively) (t=3.610,8.947,11.091 and 10.738,respectively; all P＜ 0.01).The incidence of diarrhea in the treatment group was higher than the control group (28.6％ vs 10.2％ ; x2 =5.288,P=0.021).In multivariate logistic regression analysis,the independent factors associated with SVR were metformin treatment (P =0.009) and HOMA-IR＜ 2 at week 24 of treatment (P=0.011 ). Conclusion The combination of metformin,peginterferon alfa-2a and ribavirin improves insulin sensitivity and increases SVR rate of patients with hepatitis C genotype 1 and insulin resistance with good safety profile.