扶正化瘀片联合恩替卡韦治疗慢性乙型肝炎肝纤维化的效果观察

Clinical effect of Fuzheng Huayu tablets combined with entecavir in the treatment of chronic hepatitis B liver fibrosis

目的观察扶正化瘀片(FZHY)联合恩替卡韦(ETV)治疗慢性乙型肝炎(CHB)肝纤维化的疗效与安全性。方法选取2011年4月—2013年1月在上海交通大学附属瑞金医院和上海中医药大学附属曙光医院2个中心,肝纤维化Ishak分期≥F3的CHB肝纤维化患者52例,分为FZHY联合ETV组(联合组,n=26)和安慰剂联合ETV组(对照组,n=26),分别治疗48周。治疗前后行两次肝穿刺活检,以两组的肝脏病理纤维化Ishak分期逆转率和肝组织学活动指数(HAI)炎症分级改善率等判断疗效,以心电图等为安全性指标。确定3个分析数据集(全分析集、符合方案集、安全数据集),计量资料两组间比较采用t检验或Wilcoxon检验;计数资料组间比较采用CMHχ^2法、χ^2检验或Fisher精确概率法。结果46例患者完成了治疗前后两次肝穿刺,其中联合组22例,对照组24例。治疗48周时,两组Ishak分期下降≥1级患者比例差异有统计学意义(81.8%vs 54.2%,χ^2=5.297,P=0.021)。联合组和对照组HAI分级改善率分别为59.1%、25.0%,差异有统计学意义(χ^2=6.822,P=0.009)。两组不良事件发生率、严重不良事件发生率,不良反应发生率、生命体征安全性分析、实验室安全性指标等比较,差异均无统计学意义(P值均>0.05)。结论在改善肝纤维化和肝脏炎症方面,FZHY联合ETV相较于单用ETV有显著优势,抗病毒联合抗纤维化治疗能够给CHB患者带来更好的肝组织学改善。FZHY联合ETV治疗CHB肝纤维化患者有良好的安全性。

Objective To investigate the efficacy and safety of Fuzheng Huayu tablets(FZHY)combined with entecavir(ETV)in the treatment of chronic hepatitis B(CHB)liver fibrosis.Methods A total of 52 patients with CHB liver fibrosis with an Ishak stage of≥F3 who were treated in Ruijin Hospital,Shanghai Jiao Tong University School of Medicine and Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from April 2011 to January 2013 were enrolled and divided into FZHY combined with ETV group(combination group)and placebo combined with ETV group(control group),with 26 patients in each group,and the course of treatment was 48 weeks for both groups.Liver biopsy was performed before and after these treatment;clinical outcome was determined based on the reversal rate of Ishak stage for liver fibrosis and the improvement rate of histological activity index(HAI)for inflammation grade,and safety was evaluated based on electrocardiographic findings.Three datasets(full analysis set,per-protocol set,and safety dataset)were identified for analysis;the t-test or the Wilcoxon test was used for comparison of continuous data between two groups,and the CMH chi-square test,the chi-square test,or the Fisher’s exact test was used for comparison of categorical data between groups.Results Of all 52 patients,46 underwent the two liver biopsies before and after treatment,with 22 in the combination group and 24 in the control group.At week 48 of treatment,there was a significant difference in the proportion of patients with Ishak stage reduced by≥1 stage between the combination group and the control group(81.8%vs 54.2%,χ^2=5.297,P=0.021).There was also a significant difference in the improvement rate of HAI grade between the combination group and the control group were(59.1%vs 25.0%,χ^2=6.822,P=0.009).There were no significant differences between the two groups in the incidence rates of adverse events and serious adverse events,the safety analysis of vital signs,and laboratory safety indicators(all P>0.05).Conclusion FZHY combined with ETV has significant advantages over ETV alone in improving liver fibrosis and inflammation,and antiviral therapy combined with anti-fibrosis therapy can bring better hepatic histological improvement for CHB patients.FZHY combined with ETV has good safety in the treatment of patients with CHB liver fibrosis.