Effect of Nucleos(t)ide Analogues Withdrawal on Survival Outcomes in Patients With Hepatitis B Virus‐Related Acute‐on‐Chronic Liver Failure

ABSTRACT Background/Aims Nucleos(t)ide analogues (NA) withdrawal is an important cause of hepatitis B virus (HBV) infection relapse or flare, potentially triggering HBV‐related acute‐on‐chronic liver failure (HBV‐ACLF). Although both NA withdrawal and spontaneous severe acute exacerbation (SAE) of chronic hepatitis B are recognised HBV‐ACLF triggers, comparative evidence regarding their distinct clinical trajectories remains absent. This multicenter retrospective cohort study sought to determine whether NA withdrawal independently predicts adverse outcomes in HBV‐related ACLF compared to SAE‐induced cases. Methods We retrospectively enrolled consecutive patients with HBV‐ACLF admitted to four tertiary hospitals in China. The relationship between NA withdrawal and all‐cause mortality in HBV‐ACLF patients was evaluated using multivariate Cox regression analysis. Additionally, sensitivity analyses including propensity score matching (PSM) and inverse probability treatment weighting (IPTW) were performed. Results Among the 313 HBV‐ACLF patients, 66 patients (21.1%) experienced NA withdrawal. HBV‐ACLF patients in the NA‐withdrawal group exhibited lower liver enzyme levels and higher infection rates at diagnosis compared with those in the NA‐naïve group. Multivariate Cox regression models indicated that, after adjusting for demographic and clinical confounders, NA withdrawal was significantly associated with 90‐day mortality (hazard ratio [HR], 1.610; 95% confidence interval [CI], 1.095–2.365; p = 0.015) and 180‐day mortality (HR, 1.549; 95% CI, 1.057–2.271; p = 0.025). Notably, the association remained consistent following PSM and IPTW. Conclusions NA withdrawal is an independent risk factor for death in patients with HBV‐ACLF, underlining the importance of adherence to NA therapy in patients with chronic hepatitis B.