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
In brief
Hepatitis B antigen clearance linked to 5.17 more years of survival
In a Chinese cohort followed for a median 11.1 years, patients with sustained loss of hepatitis B surface antigen and very low virus levels had lower risks of cirrhosis, liver cancer and death than matched patients with persistent infection. Most clearances occurred spontaneously. Because this was an observational study, the survival difference shows an association, not proof that clearance caused longer life.
- Journal
- The Lancet regional health. Western Pacific (Q1)
- Published
- 21 September 2026
- Study design
- Prospective / inception cohort
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Ying Zhang, Wentao Yao, Jie Jiang, Jiao Qian, Xiaoxiao Chen, Qingyu Jiang, et al.
- PMID
- 42825112
- DOI
- 10.1016/j.lanwpc.2026.101983
Why clinicians should know about it
- Picked for Epidemiology (paper of the day, 5 October 2026): Prospective cohort of CHB patients with long-term outcomes
Abstract
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).
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.