Dai Chia-Yen, Huang Jee-Fu, Hsieh Ming-Yen, Hou Nai-Jen, Lin Zu-Yau, Chen Shinn-Chern, Hsieh Ming-Yuh, Wang Liang-Yen, Chang Wen-Yu, Chuang Wan-Long, Yu Ming-Lung
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd, Kaohsiung 807, Taiwan.
J Hepatol. 2009 Apr;50(4):712-8. doi: 10.1016/j.jhep.2008.12.017. Epub 2009 Feb 6.
BACKGROUND/AIMS: Insulin resistance (IR) might be associated with hepatitis C virus (HCV) infection. This study aimed to elucidate impact of IR and beta-cell function on the response to peginterferon-alpha (PEG-IFN)/ribavirin combination therapy in chronic hepatitis C (CHC) patients.
Three hundred and thirty patients without overt diabetes were treated with combination therapy with (PEG-IFN)/ribavirin for 24 weeks. The IR and beta-cell function were evaluated by homeostasis model assessment of IR (HOMA-IR) and homeostasis model assessment of beta-cell function (HOMA-beta) before treatment.
HCV genotype, pretreatment HCV RNA level and pretreatment HOMA-IR, but not HOMA-beta, were independent factors associated with sustained virologic response (SVR). In 150 patients with genotype 1b infection, pretreatment HCV RNA level, HOMA-IR and age were independent predictors for SVR. The significantly lower SVR rate in high HOMA-IR patients was observed in 76 patients with high HCV RNA levels (>or=400,000IU/mL) who were defined as 'difficult-to-treat' patients. The mean HOMA-IR of 'difficult-to-treat' patients was significantly lower in 42 sustained responders than in 34 non-responders.
IR was associated with SVR to (PEG-IFN)/ribavirin therapy for CHC, especially among 'difficult-to-treat' patients. These findings suggested clinical application of pretreatment HOMA-IR could enable treatment outcome to be predicted and treatment regimens to be determined.
背景/目的:胰岛素抵抗(IR)可能与丙型肝炎病毒(HCV)感染相关。本研究旨在阐明IR和β细胞功能对慢性丙型肝炎(CHC)患者聚乙二醇干扰素-α(PEG-IFN)/利巴韦林联合治疗反应的影响。
330例无明显糖尿病的患者接受(PEG-IFN)/利巴韦林联合治疗24周。治疗前通过稳态模型评估IR(HOMA-IR)和β细胞功能稳态模型评估(HOMA-β)来评估IR和β细胞功能。
HCV基因型、治疗前HCV RNA水平和治疗前HOMA-IR是与持续病毒学应答(SVR)相关的独立因素,而HOMA-β不是。在150例基因型1b感染患者中,治疗前HCV RNA水平、HOMA-IR和年龄是SVR的独立预测因素。在76例HCV RNA水平高(≥400,000IU/mL)的患者中观察到高HOMA-IR患者的SVR率显著较低,这些患者被定义为“难治性”患者。42例持续应答者中“难治性”患者的平均HOMA-IR显著低于34例无应答者。
IR与CHC患者对(PEG-IFN)/利巴韦林治疗的SVR相关,尤其是在“难治性”患者中。这些发现提示治疗前HOMA-IR的临床应用能够预测治疗结果并确定治疗方案。