Rao Hui-Ying, Li Jing, Zhang Lan-Fang, Chen Huan-Yong, Zhu Li-Min, Wei Lai, Sun Yan, Wang Hao
Peking University People's Hospital, Peking University Hepatology Institute, Beijing 100044, China.
Zhonghua Yi Xue Za Zhi. 2008 Jan 8;88(2):96-100.
To access the effect of pegylated interferon (PEGIFN) beta-1a on the reduction of liver fibrosis in chronic hepatitis C (HVC).
Twenty-one patients with chronic HVC were divided into two groups randomly and treated with recombinant human PEGIHN-beta-1a (n = 13) or PEGIHN-beta-1a plus ribavirin (RBV) (n = 8) for 24 weeks, and then followed up for another 24 weeks. The clinical manifestations were observed and the clinical effects were evaluated. Biopsy was conducted before and after the treatment to analyze the histological activity index (HAI) and staging of fibrosis according the modified Knodell scoring system. Immunohistochemical analysis was used to examine the levels of alpha-smooth muscle actin (alpha-SMA), marker of activation of hepatic stellate cells (HSCs), and collagen type III in the HSCs.
Sustained viral response (SVR) was achieved in 7 patients, and end-of-treatment virologic response (ETVR) was achieved in 9 patients. The HAI after treatment was 4.3 +/- 2.2, significantly lower than that before treatment (6.6 +/- 2.2, t = 4.77, P < 0.01). The fibrosis score after treatment was 1.1 +/- 1.1, significantly lower than that before treatment (1.7 +/- 1.2, t = 1.92, P < 0.05). The alpha-SMA score after treatment was 14 +/- 8, significantly lower than that before treatment (20 +/- 11, t = 2.15, P < 0.05). The integrated light density of collagen type III after treatment was 10 +/- 10, significantly lower than that before treatment (16 +/- 12, t = 1.83, P < 0.05). The improvement levels of fibrosis, alpha-SMA score, and integrated light density of collagen type III of the patients with SVR were all better than those of the patients without SVR; however, the differences were all not significant. The patients with combination therapy, female patients, and the patients with the HCV RNA < 2 x 10(6) copies/ml before treatment all showed higher levels in histology response. HAI, alpha-SMA level, and collagen type III values were all significantly correlated with the values of the semiquantitative indexes of fibrosis (all P < 0.01).
Resisting hepatitis virus C and inhibiting and reversing the fibrotic progress, IFN-beta-1a therapy improves the liver histology of chronic HVC regardless of the viral response.
评估聚乙二醇化干扰素(PEGIFN)β-1a对慢性丙型肝炎(HVC)肝纤维化减轻的作用。
21例慢性HVC患者随机分为两组,分别接受重组人PEGIFN-β-1a(n = 13)或PEGIFN-β-1a联合利巴韦林(RBV)(n = 8)治疗24周,然后再随访24周。观察临床表现并评估临床疗效。治疗前后进行活检,根据改良的Knodell评分系统分析组织学活动指数(HAI)和纤维化分期。采用免疫组织化学分析检测肝星状细胞(HSCs)中α-平滑肌肌动蛋白(α-SMA)水平、HSCs激活标志物以及III型胶原蛋白水平。
7例患者获得持续病毒学应答(SVR),9例患者获得治疗结束时病毒学应答(ETVR)。治疗后HAI为4.3±2.2,显著低于治疗前(6.6±2.2,t = 4.77,P < 0.01)。治疗后纤维化评分1.1±1.1,显著低于治疗前(1.7±1.2,t = 1.92,P < 0.05)。治疗后α-SMA评分为14±8,显著低于治疗前(20±11,t = 2.15,P < 0.05)。治疗后III型胶原蛋白的积分光密度为10±10,显著低于治疗前(16±12,t = 1.83,P < 0.05)。SVR患者的纤维化改善水平、α-SMA评分及III型胶原蛋白积分光密度均优于无SVR的患者;但差异均无统计学意义。联合治疗的患者、女性患者以及治疗前HCV RNA < 2×10⁶拷贝/ml的患者在组织学应答方面均表现出较高水平。HAI、α-SMA水平及III型胶原蛋白值均与纤维化半定量指标值显著相关(均P < 0.01)。
无论病毒应答情况如何,IFN-β-1a治疗通过抗丙型肝炎病毒以及抑制和逆转纤维化进程,改善了慢性HVC的肝脏组织学。