干扰素β-1a治疗慢性丙型肝炎对肝纤维化的影响

目的 用干扰素β-1a(IFN-β-1a)单独或联合利巴韦林(RBV)治疗慢性丙型肝炎患者,比较治疗前后的肝组织学的变化.方法 慢性丙型肝炎患者21例,其中男14例、女7例,平均年龄(50±7)岁,随机分入IFN-β-1a单独治疗组(13例)和IFN-β-1a联合RBV治疗组(8例).共治疗24周,停药后观察24周.治疗前1年内行第1次肝组织活检,最后1次随访时(第48周)行第2次肝组织活检.对治疗前后的肝活检组织进行炎症坏死(HAI)积分、纤维化评分以及α-平滑肌肌动蛋白(α-SMA)、Ⅲ型胶原的免疫组化染色.结果 (1)21例患者7例获得了持续病毒学应答(SVR).(2)21例患者治疗前HAI(6.6±2.2)分,治疗后(4.3±2.2)分,治疗后HAI积分有明显改善(t=4.77,P＜0.01);SVR组与非SVR组患者的HAI改善程度的差异有统计学意义(t=2.04,P＜0.05).(3)治疗前纤维化评分为(1.7±1.2)分,治疗后(1.1±1.1)分,治疗后纤维化评分较治疗前有明显改善(t=1.92,P＜0.05).SVR中有71.40%的患者获得了肝纤维化改善,未获得SVR的患者中有42.96%获得了肝纤维化改善.(4)21例患者治疗前后α-SMA和Ⅲ型胶原的表达有差异(t值分别为2.15、1.83,均P＜0.05).(5)联合治疗的患者肝组织学评分更易获得改善.(6)肝组织纤维化评分与肝组织HAI积分、α-SMA评分和Ⅲ型胶原积分光密度值之间均呈正相关,相关系数分别为0.805、0.942、0.949,均P＜0.01).结论 无论患者是否获得了病毒学应答,IFN-β-1a能有效改善慢性丙型肝炎患者的肝组织情况.α-SMA评分和Ⅲ型胶原积分光密度值能较好地反映肝纤维化程度.IFN-β-1a不仅能抗丙型肝炎病毒,还能直接抑制和扭转肝纤维化的进展.

Effect of pegylated interferon β-1a therapy on the liver fibrosis in chronic hepatitis C:a semi-quantitative analysis

Objective To access the effect of pegylated interferon(PEGIFN)β-1a on the reduction of liver fibrosis in chronic hepatitis C(HVC).Methods Twenty-one patients with chronic HVC were divided into two groups randomly and treated with recombinant human PEGIHN-β-1a(n=13)or PEGIHN-β-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 α-smooth muscle actin(α-SMA),marker of activation of hepatic stellate cells(HSCs),and collagen type Ⅲ in the HSCs.Resalts 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 α-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 treratment was 10±10,significantly lower than that before treatment(16±12,t=1.83,P＜0.05).The improvement levels of fibrosis,α-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＜2×106 copies/ml before treatment all showed higher levels in histology response.HAI,α-SMA level,and collagen type Ⅲ values were all significantly correlated with the values of the semiquantitative indexes of fibrosis(all P＜0.01).Conclusion Resisting hepatitis virus C and inhibiting and reversing the fibrotic progress,IFN-β-1a therapy improves the liver histology of chronic HVC regardless of the viral response.