Everson G T, Balart L, Lee S S, Reindollar R W, Shiffman M L, Minuk G Y, Pockros P J, Govindarajan S, Lentz E, Heathcote E J
Section of Hepatology, Department of Medicine, University of Colorado Health Sciences Center, Denver, CO, USA.
Aliment Pharmacol Ther. 2008 Apr 1;27(7):542-51. doi: 10.1111/j.1365-2036.2008.03620.x. Epub 2008 Jan 17.
Patients with chronic hepatitis C virus and advanced fibrosis or cirrhosis are at risk for disease progression and hepatic decompensation.
To determine the effects on hepatic histology of treatment with peginterferon alfa-2a (90 or 180 mug/week) or interferon alfa-2a (3 million units three times weekly) for 48 weeks in patients with paired biopsies.
Liver biopsies were obtained at baseline and 6 months after end of treatment. Histological and virological responses were compared.
Patients attaining sustained virological response (n = 40) demonstrated the greatest improvements in fibrosis (-1.0, P < 0.0001) and inflammation (-0.65, P < 0.0001). Patients who cleared hepatitis C virus during treatment, but later relapsed (n = 59), experienced less improvement in fibrosis (-0.04, P < 0.0001) and inflammation (-0.14, P = 0.0768). Nonresponders (n = 85) showed no significant improvement in inflammation or fibrosis. Multiple regression analysis showed that the only factors contributing to improvement in fibrosis were sustained virological response (vs. nonresponder, P = 0.0005; vs. relapse, P = 0.7525) and body mass index < or =30 kg/m2 (P = 0.0995).
These findings indicate that virological response to peginterferon alfa-2a improves inflammation and fibrosis in hepatitis C virus patients with advanced fibrosis or cirrhosis. Improving virological response and maintaining ideal body weight are critical for achieving optimal histological outcomes in hepatitis C virus patients.
慢性丙型肝炎病毒感染且伴有严重纤维化或肝硬化的患者存在疾病进展和肝失代偿的风险。
确定聚乙二醇干扰素α-2a(90或180微克/周)或干扰素α-2a(300万单位,每周三次)治疗48周对有配对活检的患者肝脏组织学的影响。
在基线期和治疗结束后6个月获取肝脏活检样本。比较组织学和病毒学反应。
获得持续病毒学应答的患者(n = 40)在纤维化(-1.0,P < 0.0001)和炎症(-0.65,P < 0.0001)方面改善最大。治疗期间清除丙型肝炎病毒但后来复发的患者(n = 59)在纤维化(-0.04,P < 0.0001)和炎症(-0.14,P = 0.0768)方面改善较少。无应答者(n = 85)在炎症或纤维化方面无显著改善。多元回归分析表明,导致纤维化改善的唯一因素是持续病毒学应答(与无应答者相比,P = 0.0005;与复发者相比,P = 0.7525)和体重指数≤30 kg/m2(P = 0.0995)。
这些发现表明,对聚乙二醇干扰素α-2a的病毒学应答可改善晚期纤维化或肝硬化丙型肝炎病毒患者的炎症和纤维化。改善病毒学应答和维持理想体重对于实现丙型肝炎病毒患者最佳组织学结果至关重要。