马来酸恩替卡韦治疗中国慢性乙型肝炎主要为 B 型或 C 型的 1

StephenW

马来酸恩替卡韦治疗中国慢性乙型肝炎主要为 B 型或 C 型的 192 周治疗
徐景航 1 ，王撒 2 ，张大志 3 ，于彦彦 4 ，崇文 1 ，郑增 1 ，徐中南 5 ，李军 6 ，青茂 7 ，唐红 8 ，盛继芳 9 , 陈新月 10 , 秦宁 11 , 石广峰 12 , 谢青 13 , 张喜全 5 , 戴军 5
隶属关系
隶属关系

    1
    北京大学第一医院肝病中心感染科,北京 100094
    2
    首都医科大学北京地坛医院传染病临床与研究中心,北京 100015
    3
    重庆医科大学第二附属医院感染科,重庆 400010
    4
    北京大学第一医院肝病中心感染科,北京 100094 [email protected]。
    5
    江苏正大天庆药业有限公司，江苏省南京市 222006
    6
    南京医科大学第一附属医院感染科，江苏省南京市 210029
    7
    西南医院感染科，重庆 400038
    8
    四川省成都 610041, 华西医院感染科
    9
    浙江大学第一附属医院感染科，浙江杭州 310010
    10
    首都医科大学北京佑安医院国际医学​​科，北京 100069
    11
    华中科技大学同济医学院同济医院感染科及研究所,湖北武汉 430030
    12
    复旦大学华山医院感染科，上海 200040
    13
    交通大学医学院附属瑞金医院感染科,上海 200025

    PMID：36246814 PMCID：PMC9561570 DOI：10.12998/wjcc.v10.i28.10085

抽象的

背景：恩替卡韦 (ETV) 是一种有效的选择性核苷酸类似物，对乙型肝炎病毒 (HBV) 具有显着的活性。 ETV 马来酸盐是 ETV 的衍生化合物，据报道，在 III 期临床试验（Clinical Trials.gov 编号， NCT01926288）在第 48、96 和 144 周。

目的：研究 ETV 马来酸盐在第 192 周对主要基因型为 B 或 C 的中国 CHB 患者的抗病毒效力和安全性。

方法：在这项双盲研究中，我们将患者随机分配接受 0.5 mg/d ETV（A 组）或 ETV 马来酸盐（B 组）（比例，1:1），每人服用安慰剂片剂，持续 48 周。然后，所有患者从第 49 周开始接受 0.5 mg/d ETV 马来酸盐的开放标签治疗。主要疗效终点是 HBV DNA 水平相对于基线的降低。次要终点包括无法检测到 HBV DNA（<20 IU/mL）的患者比例、血清学反应、血清丙氨酸氨基转移酶（ALT）正常化和耐药突变的发生。

结果：对 218 名乙型肝炎 e 抗原 (HBeAg) 阳性患者和 57 名 HBeAg 阴性患者进行了分析，主要表现为基因型 B (49.82%) 或 C (48.73%)。对于 HBeAg 阳性 CHB 患者，平均 HBV DNA 水平降低（6.61 Log10 IU/mL vs 6.69 Log10 IU/mL，P > 0.05），HBV DNA < 20 IU/mL 的病毒抑制（83.33% vs 79.17%，P > 0.05) 和 HBeAg 血清学转换 (28.77% vs 20.00%, P > 0.05) 在 A 组和 B 组之间在第 192 周发生相似。但是，ALT 水平正常的患者比例存在显着差异 (91.14% vs 78.38% , P < 0.05)。对于 HBeAg 阴性 CHB 患者，在第 192 周时，A 组和 B 组在 HBV DNA 水平相对于基线的降低方面没有显着差异（6.05 Log10 IU/mL vs 6.03 Log10 IU/mL，P > 0.05），百分比HBV DNA 检测不到的患者比例（100% vs 100%，P > 0.05）和 ALT 正常化率（95.65% vs 100.00%，P > 0.05）。 A 组和 B 组之间的安全性和不良事件概况相似。A 组中的两名 HBeAg 阳性患者和 B 组中的 5 名患者对 ETV 产生了基因型耐药。

结论：长达 192 周的长期 ETV 马来酸盐治疗对主要基因分型为 B 或 C 的中国 CHB 患者是有效且安全的。

关键词：慢性乙型肝炎；恩替卡韦马来酸盐；基因型;突变;随机对照试验;治疗结果。

©作者 2022。由百视登出版集团有限公司出版。保留所有权利。
利益冲突声明

利益冲突声明：谢庆曾担任诺华、百时美施贵宝和罗氏的顾问；史广峰曾是咨询委员会或审查小组的成员，曾获得诺华、葛兰素史克和百时美施贵宝的咨询费； 石广峰曾担任诺华、百时美施贵宝、葛兰素史克和罗氏的顾问； 其他作者没有什么要声明的。

StephenW

One hundred and ninety-two weeks treatment of entecavir maleate for Chinese chronic hepatitis B predominantly genotyped B or C
Jing-Hang Xu  1 , Sa Wang  2 , Da-Zhi Zhang  3 , Yan-Yan Yu  4 , Chong-Wen Si  1 , Zheng Zeng  1 , Zhong-Nan Xu  5 , Jun Li  6 , Qing Mao  7 , Hong Tang  8 , Ji-Fang Sheng  9 , Xin-Yue Chen  10 , Qin Ning  11 , Guang-Feng Shi  12 , Qing Xie  13 , Xi-Quan Zhang  5 , Jun Dai  5
Affiliations
Affiliations

    1
    Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, Beijing 100094, China.
    2
    Clinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.
    3
    Department of Infectious Diseases, The Second Affiliated Hospital with Chongqing Medical University, Chongqing 400010, China.
    4
    Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, Beijing 100094, China. [email protected].
    5
    Jiangsu Chia-tai Tianqing Pharmaceutical Co., Ltd, Nanjing 222006, Jiangsu Province, China.
    6
    Department of Infectious Diseases, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
    7
    Department of Infectious Diseases, Southwest China Hospital, Chongqing 400038, China.
    8
    Department of Infectious Diseases, West China Hospital, Chengdu 610041, Sichuan Province, China.
    9
    Department of Infectious Diseases, The First Affiliated Hospital of Zhejiang University, Hangzhou 310010, Zhejiang Province, China.
    10
    Department of International Medicine, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China.
    11
    Department and Institute of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
    12
    Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
    13
    Department of Infectious Diseases, Ruijin Hospital, Jiaotong University School of Medicine, Shanghai 200025, China.

    PMID: 36246814 PMCID: PMC9561570 DOI: 10.12998/wjcc.v10.i28.10085

Abstract

Background: Entecavir (ETV) is a potent and selective nucleotide analog with significant activity against hepatitis B virus (HBV). ETV maleate is a derivative compound of ETV and was reported to have an efficacy and safety profile that is comparable to ETV (Baraclude) when used in Chinese patients with chronic hepatitis B (CHB) in phase III clinical trials (Clinical Trials.gov number, NCT01926288) at weeks 48, 96, and 144.

Aim: To investigate the antiviral potency and safety of ETV maleate at week 192 in Chinese CHB patients predominantly genotyped B or C.

Methods: In this double-blind study, we randomly assigned patients to receive 0.5 mg/d ETV (Group A) or ETV maleate (Group B) (ratio, 1:1), each with a placebo tablet for 48 wk. Then, all patients received open-label treatment with 0.5 mg/d ETV maleate starting at week 49. The primary efficacy endpoint was the reduction in HBV DNA levels from baseline. Secondary endpoints included the proportion of patients with undetectable HBV DNA (< 20 IU/mL), serologic response, serum alanine aminotransferase (ALT) normalization and development of resistance mutations.

Results: Two hundred eighteen patients who were hepatitis B e antigen (HBeAg) positive and 57 who were HBeAg negative were analyzed and predominantly presented with genotype B (49.82%) or C (48.73%). For the HBeAg-positive CHB patients, the mean HBV DNA level decrease (6.61 Log10 IU/mL vs 6.69 Log10 IU/mL, P > 0.05), viral suppression with HBV DNA < 20 IU/mL (83.33% vs 79.17%, P > 0.05) and HBeAg seroconversion (28.77% vs 20.00%, P > 0.05) occurred similarly between Groups A and B at week 192. However, there was a significant difference in the proportion of patients with normal ALT levels (91.14% vs 78.38%, P < 0.05). For the HBeAg-negative CHB patients, no significant difference was found between Groups A and B at week 192 in terms of reductions in HBV DNA levels from baseline (6.05 Log10 IU/mL vs 6.03 Log10 IU/mL, P > 0.05), percentages of patients who achieved undetectable HBV DNA (100% vs 100%, P > 0.05) and rates of ALT normalization (95.65% vs 100.00%, P > 0.05). Safety and adverse event profiles were similar between Groups A and B. Two HBeAg-positive patients in Group A and 5 in Group B developed genotypic resistance to ETV.

Conclusion: Long-term ETV maleate treatment for up to 192 wk is effective and safe in Chinese CHB patients predominantly genotyped as B or C.

Keywords: Chronic hepatitis B; Entecavir maleate; Genotype; Mutation; Randomized controlled trial; Treatment outcome.

©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Conflict of interest statement

Conflict-of-interest statement: Qing Xie has acted as a consultant for Novar’s, Bristol-Myers Squibb and Roche; Guang-Feng Shi has been a member of advisory committees or review panels, received consulting fees from Novar’s, GlaxoSmithKline and Bristol-Myers Squibb; Guang-Feng Shi has acted as a consultant for Novar’s, Bristol-Myers Squibb, GlaxoSmithKline and Roche; other authors have nothing to declare.

StephenW

https://doi.org/10.12998/wjcc.v10.i28.10085