恩替卡韦治疗代偿期乙型肝炎肝硬化初治患者远期组织学改善研究*

doi:10.3969/j.issn.1672-5069.2025.01.025

摘要/Abstract

摘要： 目的探讨恩替卡韦(ETV)治疗代偿期乙型肝炎肝硬化初治患者远期肝组织学逆转情况。方法 2015年3月～2019年3月我院诊治的代偿期乙型肝炎肝硬化初治患者58例,均接受ETV持续治疗5年以上。行两次肝活检,采用Metavir评分系统联合P-I-R分型标准判定组织学逆转。常规行肝脏硬度检测(LSM),应用单因素和多因素Logistic回归分析影响远期组织学逆转的因素。结果经ETV治疗5～9年,58例代偿期乙型肝炎肝硬化初治患者发生远期组织学逆转35例(60.3%);组织学逆转组有饮酒史和乙型肝炎家族史占比分别为14.3%和5.7%,显著低于组织学未逆转组的52.2%和39.1%(均P<0.05),年龄为(41.8±9.3)岁,体质指数为(22.2±1.6)kg/m²,显著小于或低于未逆转组【分别为(48.8±8.5)岁和(26.6±1.8)kg/m²,P<0.05】,HBV DNA载量和抗病毒治疗时间分别为5.6(4.1,6.9)Ig IU/ml和7.1(5.7,9.1)年,显著低于或长于未逆转组【分别为7.8(6.1,8.4)Ig IU/ml和5.6(4.7,6.1)年,P<0.05】,LSM为12.8(10.3,15.1)kPa,显著低于未逆转组【14.5(12.7,20.3)kPa,P<0.05】,肝组织炎症活动度>G3比例为14.3%,显著低于未逆转组的69.6%(P<0.05);多因素Logistic回归分析显示,年龄、基线HBV DNA载量、抗病毒治疗时间、LSM和肝组织炎症活动度是发生远期组织学逆转的独立影响因素(P＜0.05)。结论对于乙型肝炎肝硬化患者,只要肝功能代偿和持续接受抗病毒治疗时间足够长,仍有机会获得肝组织学的改善,值得长期观察。

关键词: 肝硬化, 乙型肝炎, 恩替卡韦, 组织学逆转, 影响因素

Abstract: Objective The aim of this study was to investigate liver histological reversal in patients with hepatitis B-induced compensated liver cirrhosis (LC) after long-term treatment with entecavir (ETV). Methods 58 naïve patients with compensated hepatitis B cirrhosis were enrolled in our hospital between March 2015 and March 2019, and all received initial treatment with ETV for 5 to 9 years. Double liver biopsies at presentation and at time for follow-up were performed, and independent influencing factors on long-term histological improvement were analyzed by univariate and multivariate Logistic regression analysis. Results Of the 58 naïve patients with hepatitis B-induced LC, 35 individuals (60.3%) had liver histological improvement after 5 to 9 year antiviral treatment; percentages of alcohol intake and hepatitis B family history in those with histological reversal were 14.3% and 5.7%, both much lower than 52.2% and 39.1%(both P<0.05), age at enrollment was (41.8±9.3)yr, body mass index was (22.2±1.6)kg/m², both much younger or less than [(48.8±8.5) yr and (26.6±1.8)kg/m², P<0.05], serum HBV DNA load and antiviral treatment period were 5.6(4.1, 6.9)Ig IU/ml and 7.1(5.7, 9.1)yrs, significantly lower or longer than [7.8(6.1, 8.4)Ig IU/ml and 5.6(4.7, 6.1)yrs, P<0.05], LSM was 12.8(10.3, 15.1)kPa, much lower than [14.5(12.7, 20.3)kPa, P<0.05], and percentage of histological activity index (HAI) >G3 was 14.3%, much lower than 69.6%(P<0.05) in patients without histological reversal; multivariate Logistic regression analysis showed that age, serum HBV DNA loads at baseline, antiviral therapy period, LSM and HAI were all the independent impacting factors for long-term histological improvement (P＜0.05). Conclusion Early initiation and enough times of ETV antiviral treatment could improve liver histological injuries, and might obtain satisfactory outcomes in patients with compensated hepatitis B cirrhosis.

Key words: Liver cirrhosis, Hepatitis B, Entecavir, Histological reversal, Influencing factors

叶鹏, 杨本场, 茅明. 恩替卡韦治疗代偿期乙型肝炎肝硬化初治患者远期组织学改善研究^*[J]. 实用肝脏病杂志, 2025, 28(1): 96-99.

Ye Peng, Yang Benchang, Mao Ming. Long-term observation of entecavir treatment for histological improvement in patients with compensated hepatitis B-induced liver cirrhosis[J]. Journal of Practical Hepatology, 2025, 28(1): 96-99.

参考文献

[1] Huang DQ, Terrault NA, Tacke F,et al. Global epidemiology of cirrhosis - aetiology, trends and predictions. Nat Rev Gastroenterol Hepatol, 2023, 20(6):388-398.
[2] Idilman R, Aydogan M, Oruncu MB, et al. Natural history of cirrhosis: changing trends in etiology over the years. Dig Dis, 2021, 39(4):358-365.
[3] Wang X, Liu H, Qi J, et al. Trends in mortality of cirrhosis in China: an analysis of the China death surveillance database from 2008 to 2020. J Clin Transl Hepatol, 2024, 12(3):236-244.
[4] 李尧, 梁健, 张春, 等. 恩替卡韦联合聚乙二醇干扰素-α2b治疗代偿期乙型肝炎肝硬化患者疗效研究. 实用肝脏病杂志, 2024, 27(2):226-229.
[5] Wang Q, Zhao H, Deng Y, et al. Validation of baveno VII criteria for recompensation in entecavir-treated patients with hepatitis B-related decompensated cirrhosis. J Hepatol, 2022, 77(6):1564-1572.
[6] Lu F, Geng JB, Zhang JW, et al. Effect of entecavir plus ganshuang granule on fibrosis and cirrhosis in patients with chronic hepatitis B. J Tradit Chin Med, 2021, 41(4):624-629.
[7] Lee KC, Cheng JS, Chang ML, et al. Comparable outcomes of decompensated chronic hepatitis B patients treated with entecavir or tenofovir: an 8-year cohort study. Hepatol Int, 2022, 16(4):799-806.
[8] Hou JL, Zhao W, Lee C, et al. Outcomes of long-term treatment of chronic HBV infection with entecavir or other agents from a randomized trial in 24 countries. Clin Gastroenterol Hepatol, 2020, 18(2):457-467.
[9] 中华医学会肝病学分会. 肝硬化诊治指南. 实用肝脏病杂志, 2019, 22(6):770-786.
[10] 陈姝延, 孙亚朦, 周家玲, 等. 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. 中华肝脏病杂志, 2022, 30(6):583-590.
[11] Shoaib N, Khan Z, Ibrahim M, et al. Dyslipidemia and impaired liver function biomarkers in patients with hepatitis B liver cirrhosis. J Taibah Univ Med Sci, 2023, 18(4):748-754.
[12] Hsu YC, Tseng CH, Su TH, et al. Pooling data to assess risks and benefits of discontinuing nucleos(t)ide analogs in patients with chronic hepatitis B: challenges and opportunities. Gut, 2022, 71(6):1238-1240.
[13] Erken R, Loukachov V, van Dort K, et al. Quantified integrated hepatitis B virus is related to viral activity in patients with chronic hepatitis B. Hepatology, 2022, 76(1):196-206.
[14] Chen S, Zhou J, Wu X, et al. Comparison of fibrosis regression of entecavir alone or combined with pegylated interferon alpha2a in patients with chronic hepatitis B. Hepatol Int, 2021, 15(3):611-620.
[15] Sun J, Li Y, Sun X, et al. Dynamic changes of the aspartate aminotransferase-to-platelet ratio and transient elastography in predicting a histologic response in patients with chronic hepatitis B after entecavir treatment. J Ultrasound Med, 2019, 38(6):1441-1448.
[16] 王维萍, 杨丹红, 张强, 等. 核苷(酸)类似物抗病毒治疗中乙型肝炎肝硬化进展为原发性肝细胞癌危险因素分析. 中华临床感染病杂志, 2020, 13(5):348-352,e370.
[17] Abu-Freha N, Estis-Deaton A, Aasla M, et al. Liver cirrhosis in elderly patients: clinical characteristics, complications, and survival-analyses from a large retrospective study. Aging Clin Exp Res, 2022, 34(9):2217-2223.
[18] 石宇婧, 张大志. 早期积极抗HBV治疗有益于降低肝癌发生风险及HBV特异性T淋巴细胞免疫功能重建. 中华肝脏病杂志, 2023, 31(3):314-315.
[19] Xing YF, Zhou DQ, He JS, et al. Clinical and histopathological features of chronic hepatitis B virus infected patients with high HBV-DNA viral load and normal alanine aminotransferase level: a multicentre-based study in China. PLoS One, 2018, 13(9):e0203220.
[20] Wang J, Wu W, Yan X, et al. HBeAg negativity is associated with more advanced liver fibrosis in patients with chronic hepatitis B: a propensity score-matching analysis. J Clin Gastroenterol, 2020, 54(9):826-831.
[21] Meier MA, Calabrese D, Suslov A, et al. Ubiquitous expression of HBsAg from integrated HBV DNA in patients with low viral load. J Hepatol, 2021, 75(4):840-847.
[22] Xie X, Lv H, Liu C, et al. HBeAg mediates inflammatory functions of macrophages by TLR2 contributing to hepatic fibrosis. BMC Med, 2021, 19(1):247.
[23] Brusilovskaya K, Hofer BS, Simbrunner B, et al. Platelet function decreases with increasing severity of liver cirrhosis and portal hypertension-a prospective study. Thromb Haemost, 2023, 123(12):1140-1150.
[24] Gotlieb N, Schwartz N, Zelber-Sagi S,et al. Longitudinal decrease in platelet counts as a surrogate marker of liver fibrosis. World J Gastroenterol, 2020, 26(38):5849-5862.
[25] Kong Y, Sun Y, Zhou J, et al. Early steep decline of liver stiffness predicts histological reversal of fibrosis in chronic hepatitis B patients treated with entecavir. J Viral Hepat, 2019, 26(5):576-585.

恩替卡韦治疗代偿期乙型肝炎肝硬化初治患者远期组织学改善研究^*

Long-term observation of entecavir treatment for histological improvement in patients with compensated hepatitis B-induced liver cirrhosis

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	吴继华, 石磊, 张肖, 徐震, 王铮. 慢性乙型肝炎与乙型肝炎病毒携带者HLA和ApoE基因多态性差异分析^*[J]. 实用肝脏病杂志, 2025, 28(1): 28-31.
[2]	王常鹤, 朱璇, 邓静, 张聪颖, 赵宇, 刘芳. 超声剪切波弹性成像联合AAR、APRI和FIB-4指数诊断慢性乙型肝炎患者肝纤维化程度效能研究^*[J]. 实用肝脏病杂志, 2025, 28(1): 32-35.
[3]	胡雨, 王静晖, 王瑶. 声触诊组织量化技术联合FIB-4指数和AST/ALT比值诊断慢性乙型肝炎患者肝纤维化价值研究^*[J]. 实用肝脏病杂志, 2025, 28(1): 36-39.
[4]	王宝林, 杜潘艳, 李小超, 侯斌. 自身免疫性肝病患者外周血CD34⁺细胞和血清白细胞介素-3水平变化及其临床意义探讨^*[J]. 实用肝脏病杂志, 2025, 28(1): 64-67.
[5]	刘斐, 姚杰, 张丽骞, 乔志飞, 高乃坤, 王磊, 刘春艳, 李福龙. 32例脓毒症相关性肝损伤患者临床特征及其影响因素分析^*[J]. 实用肝脏病杂志, 2025, 28(1): 76-79.
[6]	沈莉莉, 赵琳, 石磊. 失代偿期乙型肝炎肝硬化并发自发性细菌性腹膜炎患者第三代头孢菌素类耐药情况调查^*[J]. 实用肝脏病杂志, 2025, 28(1): 88-91.
[7]	杨慧玲, 赵文哲, 杨柳青, 杨健, 刘小静. DCE-MRI功能参数诊断代偿期和失代偿期乙型肝炎肝硬化价值研究^*[J]. 实用肝脏病杂志, 2025, 28(1): 92-95.
[8]	司同, 朱家宝, 吴彬彬. 超声联合剪切波弹性成像评估肝硬化门脉高压症患者并发高风险食管静脉曲张价值分析^*[J]. 实用肝脏病杂志, 2025, 28(1): 100-103.
[9]	朱瑞农, 宋丽群, 钱佶. 生长抑素联合内镜下治疗肝硬化并发食管胃底静脉曲张破裂出血患者疗效研究^*[J]. 实用肝脏病杂志, 2025, 28(1): 104-107.
[10]	卓宇宏, 陈平湖, 陈鸿程, 周思君, 陈小云, 范微微, 叶石才. 内镜下套扎术联合生长抑素治疗肝硬化并发食管胃底静脉曲张破裂出血患者疗效研究^*[J]. 实用肝脏病杂志, 2025, 28(1): 108-111.
[11]	王旭丽, 蔡明月, 周志明, 陈苏闽. 不同Child-Pugh分级的乙型肝炎肝硬化患者肝脏体积差异分析^*[J]. 实用肝脏病杂志, 2025, 28(1): 112-115.
[12]	许文慧, 许箐贇, 李彬彬, 潘超. 间接测热法与公式法测定失代偿期乙型肝炎肝硬化患者静息能量消耗临床意义探讨^*[J]. 实用肝脏病杂志, 2025, 28(1): 116-119.
[13]	王文栋, 梁茂全, 刘玉岩. 经颈静脉肝内门体分流术联合部分脾动脉栓塞术治疗肝硬化并发门脉高压症患者门静脉血流动力学变化研究^*[J]. 实用肝脏病杂志, 2025, 28(1): 120-123.
[14]	杨爽, 高学松, 段雪飞. 难治性原发性胆汁性胆管炎研究进展^*[J]. 实用肝脏病杂志, 2025, 28(1): 156-159.
[15]	张天挺, 许晶, 姜正伟, 嵇卉. 丙酚替诺福韦联合肝爽颗粒治疗慢性乙型肝炎患者疗效及其对肝纤维化指标的影响^*[J]. 实用肝脏病杂志, 2024, 27(6): 820-823.