Yang Sisi, Ma Xueqing, Cai Chengwei, Wang Huanqiu, Xiao Fenqiang, Yu Chengbo
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Neurosurgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Front Med (Lausanne). 2021 Mar 15;8:637126. doi: 10.3389/fmed.2021.637126. eCollection 2021.
Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are equally recommended as the first-line antiviral treatments for chronic hepatitis B (CHB) at present. We aimed to compare the long-term efficacy and safety between ETV and TDF therapy in CHB patients who had not received nucleoside analog treatment. In this single-center retrospective study, 414 patients who received ETV (290 patients) or TDF (124 patients) therapy at our center from January 2017 to May 2019 were included. To reduce the imbalance of baseline variables, propensity score matching (PSM) was employed to yield 124 pairs of patients at a ratio of 1:1 based on the treatment regimen. After PSM, the cumulative rate of patients who achieved complete virological response (CVR) was not different by drug therapy at each inspection time (1, 3, 6, 12, 18, and 24 months). Subgroup analysis on HBeAg status and level of HBV DNA demonstrated that evolution of proportion of achieving CVR was not significantly different between groups. Despite the insignificant incidence of HBsAg seroclearance in either group, patients in TDF group achieved higher on-treatment HBsAg decline at each inspection time (1, 3, 6, 9, 12, 18, and 24 months), 0.39, 0.51, 0.61, 0.64, 0.68, 0.76, and 0.91 log IU/mL, respectively; while the corresponding reduction were 0.27, 0.37, 0.40, 0.45, 0.48, 0.55, and 0.66 log IU/mL in ETV group ( < 0.05). In subgroup analysis, we found that the significant difference still existed in patients with high baseline HBsAg level (>3 log IU/mL). Additionally, the proportion of patients who achieved on-treatment HBsAg decline >1 log IU/mL in TDF and ETV group was 33.3 and 17.1% ( < 0.01) at the 12th month, 44.4 and 29.5% ( = 0.03) at the 24th month, respectively. Mean increase in serum creatinine from baseline was 0.10 and 0.08 mg/dL in TDF and ETV group ( = 0.11), with no patient experienced acute kidney injury. TDF has higher potency in reducing HBsAg than ETV in this study. Considering the effect still existed in patients with high HBsAg level (>3 log IU/mL), TDF might be a superior therapeutic regimen combining with its relatively safety.
目前，替诺福韦酯（TDF）和恩替卡韦（ETV）均同样被推荐作为慢性乙型肝炎（CHB）的一线抗病毒治疗药物。我们旨在比较ETV和TDF治疗未接受过核苷类似物治疗的CHB患者的长期疗效和安全性。在这项单中心回顾性研究中，纳入了2017年1月至2019年5月在我们中心接受ETV治疗（290例患者）或TDF治疗（124例患者）的414例患者。为减少基线变量的不平衡，采用倾向得分匹配（PSM）以1:1的比例产生124对患者，基于治疗方案进行匹配。PSM后，在每个检查时间点（1、3、6、12、18和24个月），实现完全病毒学应答（CVR）的患者累积率在药物治疗组间无差异。对HBeAg状态和HBV DNA水平的亚组分析表明，两组间实现CVR的比例变化无显著差异。尽管两组中HBsAg血清学清除率均较低，但TDF组患者在每个检查时间点（1、3、6、9、12、18和24个月）的治疗期间HBsAg下降幅度更高，分别为0.39、0.51、0.61、0.64、0.68、0.76和0.91 log IU/mL；而ETV组相应的下降幅度为0.27、0.37、0.40、0.45、0.48、0.55和0.66 log IU/mL（P<0.05）。在亚组分析中，我们发现基线HBsAg水平较高（>3 log IU/mL）的患者中仍存在显著差异。此外，在第12个月时，TDF组和ETV组治疗期间HBsAg下降幅度>1 log IU/mL的患者比例分别为33.3%和17.1%（P<0.01），在第24个月时分别为44.4%和29.5%（P=0.03）。TDF组和ETV组血清肌酐较基线的平均升高分别为0.10和0.08 mg/dL（P=0.11），无患者发生急性肾损伤。在本研究中，TDF降低HBsAg的效力高于ETV。考虑到在HBsAg水平较高（>3 log IU/mL）的患者中仍有效果，TDF可能是一种更优的治疗方案，且其安全性相对较好。
