2024 年第 1 期 第 19 卷

富马酸丙酚替诺福韦和替诺福韦酯治疗慢性乙型肝炎初治患者的临床效果及应答不佳的处理方案探讨

Clinical effect and discussion on the solution of poor response of tenofovir alafenamide fumarate and tenofovir dixil in the treatment of chronic hepatitis B patients undergoing initial treatment

作者：黎清梅 江建宁 苏明华 苏土梅 殷倩冰 胡伯斌 王荣明 梁蘅恺 韦璐 冯彦菲

英文作者：Li Qingmei Jiang Jianning Su Minghua Su Tumei Yin Qianbing Hu Bobin Wang Rongming Liang Hengkai Wei Lu Feng Yanfei

单位：广西医科大学第一附属医院感染性疾病科教育部区域性高发肿瘤早期防治研究重点实验室，南宁530021

英文单位：Department of Infectious Diseases the First Affiliated Hospital of Guangxi Medical University Key Laboratory of High-Incidence-Tumor Prevention and Treatment Ministry of Education Nanning 530021 China

关键词：慢性乙型肝炎；富马酸丙酚替诺福韦；替诺福韦酯；完全病毒学应答

英文关键词：ChronichepatitisB;Tenofoviralafenamidefumarate;Tenofovirdiaxil;Completevirologicalresponse

• 摘要：

• 目的  探讨富马酸丙酚替诺福韦（TAF）和替诺福韦酯（TDF）对初次治疗慢性乙型肝炎（CHB）患者的效果及应答不佳的处理方案。方法  回顾性收集163例2018年1月至2022年6月广西医科大学第一附属医院感染性疾病科CHB患者的临床资料，根据服用药物不同分为TDF组（85例）和TAF组（78例）。采用Logistic回归方法分析影响乙型肝炎病毒（HBV）DNA应答的因素，并对基线HBV DNA、基线丙氨酸转氨酶（ALT）、药物、性别、基线乙型肝炎e抗原（HBeAg）进行分层分析。分析治疗48周未获得完全病毒学应答（HBV DNA＜20 kIU/L）的CHB患者结局。结果  多因素Logistic回归分析表明性别、基线ALT、基线HBV DNA、基线HBeAg是患者获得完全病毒学应答的影响因素，其中女性、基线ALT异常、基线HBV DNA载量低、基线HBeAg阴性患者更容易获得完全病毒学应答（均P＜0.05）。治疗48周72.4%（118/163）的患者获得完全病毒学应答，TAF组完全病毒学应答率高于TDF组（P＜0.05），基线HBV DNA≤2×105 kIU/L组完全病毒学应答率高于基线HBV DNA＞2×105 kIU/L组（P＜0.001）。在治疗48周未获得完全病毒学应答的患者中，继续按原方案治疗48周者，78.6%（11/14）获得完全病毒学应答；转换或加用另一种核苷（酸）类抗病毒药治疗48周者，81.0%（17/21）获得完全病毒学应答。结论  TDF和TAF均能有效抑制HBV DNA复制，且TAF疗效不劣于TDF；患者HBV DNA水平是发生完全病毒学应答的重要影响因素。对于治疗48周发生应答不佳的患者应及时换药或在联合用药基础上增加剂量，促进患者获得完全病毒学应答及减少耐药的发生。

• Objective  To investigate the efficacy of tenofovir alafenamide fumarate (TAF) and tenofovir dixil (TDF) and the solution of poor response in previously untreated chronic hepatitis B (CHB) patients. Methods  The clinical data of 163 CHB patients admitted to Department of Infectious Diseases, the First Affiliated Hospital of Guangxi Medical University from January 2018 to June 2022 were collected. They were divided into TDF group (85 cases) and TAF group (78 cases) according to different drugs. Factors influencing hepatitis B virus (HBV) DNA response were analyzed by Logistic regression analysis, and baseline HBV DNA, baseline alanine aminotransferase (ALT), drug, gender, and baseline hepatitis B e antigen (HBeAg) were stratified analyzed. The outcomes of CHB patients who did not receive complete virology response (HBV DNA＜20 kIU/L) after 48 weeks of treatment were analyzed. Results  Multivariate Logistic regression analysis showed that gender, baseline ALT, baseline HBV DNA and baseline HBeAg were the influencing factors of complete viral response, of which female, abnormal baseline ALT, low baseline HBV DNA load and negative baseline HBeAg were more likely to obtain complete virological response (all P＜0.05). After 48 weeks of treatment, 72.4% (118/163) patients achieved complete virological response, complete virological response rate was higher in the TAF group than that in the TDF group (P＜0.05). The complete virological response rate in the group of baseline HBV DNA ≤2×105 kIU/L was higher than that in the group of baseline HBV DNA＞2×105 kIU/L (P＜0.001). For patients who did not obtain a complete virological response after 48 weeks of treatment, 78.6% (11/14) obtained a complete virological response after followed 48 weeks of treatment by the original regimen. A complete virological response was achieved by 81.0% (17/21) after 48 weeks of conversion or addition to another nucleoside (acid) antiviral. Conclusions  Both TDF and TAF can effectively inhibit HBV DNA replication, and the efficacy of TAF is not inferior to that of TDF. The level of HBV DNA is an important factor in the achievement of complete virological response. For patients with poor response after 48 weeks of treatment, drugs should be changed in time or the drug dose should be increased to promote the rate of complete virological response and reduce the occurrence of drug resistance.