The Lancet regional health. Western Pacific · 2026
HBsAg seroclearance with HBV DNA <100 IU/mL and long-term risks of adverse liver events, all-cause mortality, and cause-specific mortality in chronic hepatitis B: a prospective cohort study.
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Zhang Ying, Yao Wentao, Jiang Jie, Qian Jiao, Chen Xiaoxiao, Jiang Qingyu, Yan Yuxiang, Wang Siyu, Bai Huanjie, He Chu, Zhu Liguo, Jiang Tao, Hu Zhibin, Shen Hongbing, Zhai Xiangjun, Song Ci
Аннотация
BACKGROUND: Sustained HBsAg seroclearance with HBV DNA suppression is associated with favorable outcomes in chronic hepatitis B (CHB), but its associations with overall survival and cause-specific mortality remain insufficiently quantified.
METHODS: In a prospective, multicenter, community-based cohort of 6018 Chinese CHB patients, sustained HBsAg seroclearance with HBV DNA <100 IU/mL was modeled as a time-dependent exposure using propensity score-matched Cox regression. We estimated population attributable fractions (PAFs) for burden associated with persistent infection and restricted mean survival time (RMST) for survival difference.
FINDINGS: During a median 11.1-year follow-up, 1029 participants with sustained HBsAg seroclearance and HBV DNA <100 IU/mL (97.0% spontaneously) were compared with 2931 matched participants with persistent infection. This serovirological state was associated with lower risks of cirrhosis (adjusted hazard ratio [aHR], 0.45; 95% CI, 0.27-0.74) and hepatocellular carcinoma (aHR, 0.52; 95% CI, 0.33-0.81). It was also associated with lower all-cause mortality (aHR, 0.47; 95% CI, 0.36-0.60), as well as liver-related, extrahepatic cancer-related, and cardiovascular mortality. The RMST difference was 5.17 years within the observed age range.
INTERPRETATION: Sustained HBsAg seroclearance accompanied by very low HBV DNA levels was associated with lower risks of adverse liver outcomes and selected extrahepatic mortality, as well as longer RMST, highlighting the prognostic relevance of this serovirological state for long-term risk stratification in CHB.
FUNDING: National Natural Science Foundation of China (82373654, 82674792); Jiangsu Provincial Key Discipline of Epidemiology (ZDXK202250); Scientific Research Project of Jiangsu Provincial Health Commission (H2023041); Science and Technology Plan Project of Jiangsu Provincial Disease Control and Prevention Administration (JSJK2026M00015).
METHODS: In a prospective, multicenter, community-based cohort of 6018 Chinese CHB patients, sustained HBsAg seroclearance with HBV DNA <100 IU/mL was modeled as a time-dependent exposure using propensity score-matched Cox regression. We estimated population attributable fractions (PAFs) for burden associated with persistent infection and restricted mean survival time (RMST) for survival difference.
FINDINGS: During a median 11.1-year follow-up, 1029 participants with sustained HBsAg seroclearance and HBV DNA <100 IU/mL (97.0% spontaneously) were compared with 2931 matched participants with persistent infection. This serovirological state was associated with lower risks of cirrhosis (adjusted hazard ratio [aHR], 0.45; 95% CI, 0.27-0.74) and hepatocellular carcinoma (aHR, 0.52; 95% CI, 0.33-0.81). It was also associated with lower all-cause mortality (aHR, 0.47; 95% CI, 0.36-0.60), as well as liver-related, extrahepatic cancer-related, and cardiovascular mortality. The RMST difference was 5.17 years within the observed age range.
INTERPRETATION: Sustained HBsAg seroclearance accompanied by very low HBV DNA levels was associated with lower risks of adverse liver outcomes and selected extrahepatic mortality, as well as longer RMST, highlighting the prognostic relevance of this serovirological state for long-term risk stratification in CHB.
FUNDING: National Natural Science Foundation of China (82373654, 82674792); Jiangsu Provincial Key Discipline of Epidemiology (ZDXK202250); Scientific Research Project of Jiangsu Provincial Health Commission (H2023041); Science and Technology Plan Project of Jiangsu Provincial Disease Control and Prevention Administration (JSJK2026M00015).