[Antiviral and antifibrotic therapies reduce occurrence of hepatocellular carcinoma in patients with chronic hepatitis B and liver fibrosis: a 144-week prospective cohort study].
[Antiviral and antifibrotic therapies reduce occurrence of hepatocellular carcinoma in patients with chronic hepatitis B and liver fibrosis: a 144-week prospective cohort study].
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DOI：
10.12122/j.issn.1673-4254.2019.06.02
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发表时间：
2019-06-30
影响因子：
--
通讯作者：
Yang, Dinghua
中科院分区：
文献类型：
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作者：
Zhou, Yuchen;Hu, Chengguang;Yang, Dinghua
目的：比较不同抗病毒和抗纤维化方案在慢性乙型肝炎（CHB）合并肝纤维化患者中的疗效和安全性，以及与这些治疗相关的肝细胞癌（HCC）发生率。
方法：本项随访队列研究纳入了2010年6月至2018年6月在南方医院接受抗病毒治疗的840例慢性乙型肝炎合并肝纤维化患者。将患者按性别、年龄（差异≤5岁）、HBeAg状态和肝脏硬度测量值（LSM）匹配分为3个队列，分别接受3种抗病毒药物（恩替卡韦、替诺福韦酯和阿德福韦酯）治疗；每个队列再分为2组，其中一组联合复方鳖甲软肝片治疗。在144周时比较3个队列以及6个组之间的乙肝病毒DNA累计转阴率、谷丙转氨酶（ALT）复常率、肝纤维化逆转情况以及肝细胞癌发生率。
结果：144周时共有749例患者可进行随访。与基线数据相比，6个组在治疗过程中乙肝病毒DNA累计转阴率逐渐升高，谷丙转氨酶异常率随时间显著下降（均P < 0.001）。与单独使用任何一种抗病毒药物相比，联合治疗均具有显著更好的抗纤维化效果（恩替卡韦队列2的卡方值 = 11.345，替诺福韦酯队列2的卡方值 = 10.160，阿德福韦酯队列2的卡方值 = 6.358；均P < 0.05）。在144周时，恩替卡韦组、恩替卡韦联合复方鳖甲软肝片组、阿德福韦酯组以及阿德福韦酯联合复方鳖甲软肝片组的肝细胞癌发生率分别为2.2%、1.7%、1.7%和3.3%，两个队列（4组）之间无显著差异（卡方值 = 6.813，P = 0.138）。在观察结束时，替诺福韦治疗的2个组中无患者发生肝细胞癌。
结论：抗病毒治疗联合抗纤维化治疗可有效逆转慢性乙型肝炎患者的肝纤维化并降低肝细胞癌发生率；在3种抗病毒药物中，替诺福韦酯可能是降低这些患者肝细胞癌发生率的更好选择。
OBJECTIVE: To compare the efficacy and safety of different antiviral and antifibrotic regimens in patients with chronic hepatitis B (CHB) and hepatic fibrosis and the incidence of hepatocellular carcinoma (HCC) associated with these therapies.METHODS: A total of 840 patients with CHB and concurrent hepatic fibrosis, who received antiviral therapy in Nanfang Hospital between June, 2010 and June, 2018, were enrolled in this follow-up cohort study. The patients were assigned to 3 cohorts matched for gender, age (difference≤5 years), HBeAg status and liver stiffness measurement (LSM) for treatment with one of the 3 antiviral drugs, namely entecavir, tenofovir dipivoxil and adefovir dipivoxil; each cohort was divided into 2 groups, with one of the groups having a combined treatment with Fufang Biejiaruangan tablet. The cumulative negative conversion rate of HBV DNA, normalization rate of ALT, hepatic fibrosis regression and the incidence of HCC were compared among the 3 cohorts and across the 6 groups at 144 weeks.RESULTS: A total of 749 patients were available to follow-up at 144 weeks. Compared with the baseline data, the cumulative negative conversion rate of HBV DNA increased gradually and the abnormal rate of ALT decreased significantly over time during the treatment in all the 6 groups (all P < 0.001). Compared with the any of the antiviral drugs used alone, the combined treatments all resulted in significantly better antifibrotic effects (chiETV cohort2=11.345, chiTDF cohort2=10.160, chiADV cohort2=6.358; all P < 0.05). At 144 weeks, the incidence of HCC were 2.2%, 1.7%, 1.7% and 3.3% in enecavir group, enecavir with Biejiaruangan tablet group, adefovir group, and adefovir with Biejiaruangan tablet group, respectively, showing no significant difference between the two cohorts (4 groups; chi2=6.813, P=0.138). None of the patients in the 2 groups with tenofovir treatment had HCC by the end of the observation.CONCLUSIONS: Antiviral therapy combined with antifibrotic therapy can effectively reverse hepatic fibrosis and reduce the incidence of HCC in patients with CHB; among the 3 antiviral drugs, tenofovir dipivoxil can be a better option for reducing the incidence of HCC in these patients.