长期抗病毒治疗乙型肝炎肝硬化患者的组织学逆转率和临床改善情况  

Histological regression and clinical benefits in patients with liver cirrhosis after long-term anti-HBV treatmeht

作　　者：陈姝延 孙亚朦[1] 周家玲 吴晓宁[1] 孟彤彤 王冰琼 刘晖[2] 王泰龄[3] 邵晨[2] 赵欣宇 徐小倩 孔媛媛 欧晓娟[1] 贾继东[1] 尤红[1] Chen Shuyan;Sun Yameng;Zhou Jialing;Wu Xiaoning;Meng Tongtong;Wang Bingqiong;Liu Hui;Wang Tailing;Shao Chen;Zhao Xinyu;Xu Xiaqian;Kong Yuanyuan;Ou Xiaojuan;Jia Jidong;You Hong(Liver Research Center,Beijing Friendship Hospital,Capital Medical University,National Clinical Research Center for Digestive Diseases,Beijing 100050,China;Department of Pathology,Beijing Youan Hospital,Capial Medical University,Beijing 100069,China;Deparment of Pathology,China-Japan Friendship Hospital,Beijing 100029,China;Clinical Epidemiology and EBM Unit,Bejing Friendship Hospilal,Capilal Medical University,Bijing Clinical Research Institute,Bijing 100050,China)

机构地区：[1]首都医科大学附属北京友谊医院肝病中心,国家消化系统疾病临床医学研究中心,北京100050 [2]首都医科大学附属北京佑安医院病理科,北京100069 [3]中日友好医院病理科,北京100029 [4]首都医科大学附属北京友谊医院,北京市临床医学研究所临床流行病学与循证医学研究室,北京100050

出　　处：《中华肝脏病杂志》2022年第6期583-590,共8页Chinese Journal of Hepatology

基　　金：“十三五”国家科技重大专项(2018ZX10302204)。

摘　　要：目的探讨乙型肝炎肝硬化患者长期抗病毒治疗后的组织学逆转和临床指标改善情况。方法入组符合肝活检或临床诊断标准的代偿期乙型肝炎肝硬化初治患者, 予以恩替卡韦为基础的抗病毒治疗, 每半年进行1次随访评估, 治疗第5年行肝组织病理学检查。采用Metavir系统联合"北京标准"(P-I-R评分), 评价乙型肝炎肝硬化患者治疗5年后的组织学逆转率, 并分析其丙氨酸转氨酶(ALT)、肝脏硬度值(LSM)等临床指标的改善情况。对计量资料进行Kruskal Wallis、Wilcoxon秩和检验, 对计数资料行Fisher精确检验, 用logistic回归分析法进行多因素分析。结果共入组73例具有抗病毒治疗5年肝活检标本的乙型肝炎肝硬化初治患者。根据Metavir系统和P-I-R评分, 治疗5年后肝硬化逆转率为72.6%(53/73), 其中显著逆转组患者(Metavir评分下降≥2期)占比30.1%(22/73), 轻度逆转组患者(Metavir评分下降1期或Metavir评分不变但P-I-R评分判定为逆转为主型)占比42.5%(31/73), 不逆转组患者占比27.4%(20/73)。与治疗前相比, 抗病毒治疗5年后显著逆转组、轻度逆转组及不逆转组患者血清HBV DNA、ALT、天冬氨酸转氨酶、LSM(分别由12.7 kPa降至6.4 kPa、18.1 kPa降至7.3 kPa、21.4 kPa降至11.2 kPa)及Ishak肝组织炎症活动度评分均显著降低(P值均<0.05), 血小板和白蛋白水平显著升高(P<0.05)。多因素分析提示治疗前LSM升高是治疗5年后组织学显著逆转的独立危险因素(OR=0.887, 95%CI为0.802~0.981, P=0.020)。结论长期抗病毒治疗后, 72.6%乙型肝炎肝硬化患者可发生组织学逆转, 且所有患者的临床指标均获得改善。Objective Our study aims to determine histological regression and clinical improvement after long-term antiviral therapy in hepatitis B virus-related cirthosis patients.Methods Treatment-naive chronic hepatitis B patients with histologically or clinically diagnosed liver cirrhosis were enrolled.Liver biopsies were performed after 5 years entecavir-based antiviral treatment.Patients were followed up every 6 months.Cirrhosis regression was evaluated based on Metavir system and P-I-R score.Clinical improvement was evaluated before and after the long-term treatment.Kruskal Wallis test and Wilcoxon signed-rank test were used for continuous variables,Fisher's exact test was used for categorical variables and multivariate analysis was performed using logistic regression analysis.Results Totals of 73 patients with HBV-related liver cirrhosis were enrolled.Among them,30(41.1%)patients were biopsy proved liver cirrhosis and the remaining 43(58.9%)cirrhotic patients were diagnosed by clinical features.Based on Metavir system and P-I-R score,72.6%(53/73)patients attained histological regression.Furthermore,30.1%(22/73)were defined as significant regression(Metavir decrease>≥2 stage),42.5%(31/73)were mild regression(Metavir decreaseI stage or predominantly regressive by P-I-R system if still cirrhosis after treatment)and 27.4%(20/73)were the non-regression.Compared to levels of clinical characteristics at baseline,HBV DNA,ALT,AST,liver stifness(decreased from 12.7 to 6.4 kPa in significant regression,from 18.1 to 7.3 kPa in mild regression and from 21.4 to 11.2 kPa in non-regression)and Ishak-HAI score significantly decreased after 5 years of anti-HBV treatment,while serum levels of platelets and albumin improved remarkably(P<0.05).In multivariate analysis,only the pre-treatment liver stifness level was associated with significant regression(OR=0.887,95%Cl:0.802-0.981,P=0.020).Conclusions After long-term antiviral therapy,patients with HBV-related cirrhosis are casily to attain improvements in clinical parameters,while a ce

关 键 词：乙型肝炎 肝硬化 逆转 临床改善 

分 类 号：R512.62[医药卫生—内科学] R575.2[医药卫生—临床医学]