Center for Liver Diseases and School of Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan.
Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan.
Hepatol Int. 2022 Dec;16(6):1297-1307. doi: 10.1007/s12072-022-10411-x. Epub 2022 Sep 7.
Both entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are first-line therapies for chronic hepatitis B (CHB), but their comparative effectiveness with regards to hepatitis B surface antigen (HBsAg) seroclearance remains unclear.
This international multicenter cohort study enrolled 7697 treatment-naïve CHB patients (median age 50 years; male 66.75%) initiated on either ETV (n = 5430) or TDF (n = 2267) without baseline malignancy or immunosuppression from 23 centers across 10 countries or regions. Patients were observed for HBsAg seroclearance until death, loss to follow-up, or treatment discontinuation or switching. The incidences of HBsAg seroclearance were adjusted for competing mortality and compared between ETV and TDF cohorts with inverse probability of treatment weighting (IPTW) and also by multivariable regression analysis.
The study population was followed up for a median duration of 56.1 months with 36,929 11 person-years of observation. HBsAg seroclearance occurred in 70 ETV-treated and 21 TDF-treated patients, yielding 8-year cumulative incidence of 1.69% (95% confidence interval [CI] 1.32-2.17) for ETV and 1.34% (95% CI 0.85-2.10%), for TDF (p = 0.58). In the IPTW analysis with the two study cohorts more balanced in background covariates, the age-adjusted hazard ratio (HR) of TDF versus ETV for HBsAg seroclearance was 0.91 (95% CI 0.50-1.64; p = 0.75). Furthermore, there was no significant difference between the two medications in the multivariable competing risk regression model (adjusted sub-distributional HR 0.92 for TDF vs. ETV; 95% CI 0.56-1.53; p = 0.76).
ETV and TDF did not differ significantly in the incidence of HBsAg seroclearance, which rarely occurred with either regimen.
恩替卡韦（ETV）和富马酸替诺福韦二吡呋酯（TDF）均为慢性乙型肝炎（CHB）的一线治疗药物，但关于其乙型肝炎表面抗原（HBsAg）血清学清除的比较疗效尚不清楚。
这项国际多中心队列研究纳入了 7697 名初治 CHB 患者（中位年龄 50 岁；男性占 66.75%），他们分别接受 ETV（n=5430）或 TDF（n=2267）治疗，均无基线恶性肿瘤或免疫抑制病史，来自 10 个国家/地区的 23 个中心。患者接受观察，直至死亡、失访或治疗停药或换药。用竞争死亡率调整 HBsAg 血清学清除的发生率，并通过逆概率治疗加权（IPTW）和多变量回归分析比较 ETV 和 TDF 队列之间的差异。
研究人群中位随访时间为 56.1 个月，共观察了 36929 人年。ETV 治疗组有 70 例和 TDF 治疗组有 21 例患者发生 HBsAg 血清学清除，ETV 和 TDF 的 8 年累积发生率分别为 1.69%（95%置信区间 [CI] 1.32-2.17）和 1.34%（95% CI 0.85-2.10%）（p=0.58）。在背景协变量更为平衡的 IPTW 分析中，TDF 相对于 ETV 用于 HBsAg 血清学清除的年龄调整危险比（HR）为 0.91（95% CI 0.50-1.64；p=0.75）。此外，在多变量竞争风险回归模型中，两种药物之间没有显著差异（调整后的分布 HR 为 TDF 与 ETV 之比 0.92；95% CI 0.56-1.53；p=0.76）。
ETV 和 TDF 在 HBsAg 血清学清除的发生率上没有显著差异，两种方案都很少发生这种情况。
