Division of Gastroenterology and Hepatology, Department of Medicine, Brooke Army Medical Center, Fort Sam Houston, TX 78234, USA.
Hepatology. 2012 Aug;56(2):464-73. doi: 10.1002/hep.25661. Epub 2012 Jun 11.
Patients with chronic hepatitis C and insulin resistance are less likely to respond to anti-hepatitis C virus (HCV) therapy and are at risk for more rapid fibrosis progression. Coadministration of pioglitazone with peginterferon/ribavirin improves insulin sensitivity and increases virologic response rates in insulin-resistant HCV genotype 4 patients, but it is unclear whether this finding applies to genotype 1 patients. For this reason we randomized treatment-naive HCV genotype 1 patients with insulin resistance to receive either standard care (peginterferon alpha-2a plus ribavirin for 48 weeks, n = 73) or pioglitazone 30-45 mg/day plus standard care (n = 77) in an open-label multicenter trial. Patients randomized to pioglitazone received the drug during a 16-week run-in phase, the 48-week standard-care phase, and the 24-week untreated follow-up phase. Pioglitazone treatment improved hemoglobin A1c (HbA1c), plasma glucose, insulin levels, and homeostasis model assessment of insulin resistance score and increased serum adiponectin levels during the 16-week run-in phase and maintained these improvements during the standard-care phase. However, we observed no statistically significant difference between the two groups in the primary efficacy endpoint, the decrease from baseline to Week 12 of peginterferon alpha-2a/ribavirin treatment in mean log(10) HCV RNA titer (-3.5 ± 1.71 and -3.7 ± 1.62 IU/mL in the pioglitazone and standard-care groups, respectively, Δ = 0.21 IU/mL, P = 0.4394).
Treatment with pioglitazone before and during treatment with peginterferon alpha-2a plus ribavirin improved several indices of glycemic control in patients with chronic hepatitis C and insulin resistance, but did not improve virologic response rates compared with peginterferon alpha-2a plus ribavirin alone.
患有慢性丙型肝炎和胰岛素抵抗的患者对抗丙型肝炎病毒（HCV）治疗的反应较差，并且更容易发生更快的纤维化进展。吡格列酮与聚乙二醇干扰素/利巴韦林联合使用可改善胰岛素抵抗的 HCV 基因型 4 患者的胰岛素敏感性并提高病毒学应答率，但尚不清楚这一发现是否适用于基因型 1 患者。出于这个原因，我们将未经治疗的 HCV 基因型 1 伴胰岛素抵抗的患者随机分为两组，一组接受标准治疗（聚乙二醇干扰素 α-2a 加利巴韦林治疗 48 周，n = 73），另一组接受吡格列酮 30-45 mg/天加标准治疗（n = 77），在一项开放性、多中心试验中。随机分配至吡格列酮组的患者在 16 周的导入期、48 周的标准治疗期和 24 周的未治疗随访期接受药物治疗。吡格列酮治疗可改善血红蛋白 A1c（HbA1c）、血浆葡萄糖、胰岛素水平和稳态模型评估的胰岛素抵抗评分，并在 16 周导入期内增加血清脂联素水平，并在标准治疗期内维持这些改善。然而，我们在主要疗效终点（聚乙二醇干扰素 α-2a/利巴韦林治疗基线至 12 周时 HCV RNA 滴度的下降）上未观察到两组之间有统计学意义的差异，即吡格列酮组和标准治疗组的平均对数（10）HCV RNA 滴度分别下降（-3.5 ± 1.71 和 -3.7 ± 1.62 IU/ml，Δ=0.21 IU/ml，P=0.4394）。
在聚乙二醇干扰素 α-2a 联合利巴韦林治疗前和治疗期间使用吡格列酮可改善慢性丙型肝炎伴胰岛素抵抗患者的多项血糖控制指标，但与聚乙二醇干扰素 α-2a 联合利巴韦林单独治疗相比，并未提高病毒学应答率。
