Severe hepatitis B flares with hepatic decompensation after withdrawal of nucleos(t)ide analogues: A population-based cohort study.

Background: Finite nucleos(t)ide analogue (NUC) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB).

Aim: To quantify the incidence of severe hepatitis flares following NUC cessation in everyday clinical practice.

Methods: This population-based cohort study enrolled 10,192 patients (male 71.7%, median age 50.9 years, cirrhosis 10.7%) who had received first-line NUCs for at least 1 year before discontinuing treatment. The primary outcome was severe flare with hepatic decompensation. We used competing risk analyses to assess event incidences and associated risk factors.

Results: During a median follow-up of 2.2 years, 132 patients developed severe flares with hepatic decompensation, yielding a 4-year cumulative incidence of 1.8% (95% confidence interval [CI], 1.5%-2.2%). Significant risk factors were cirrhosis (adjusted sub-distributional hazard ratio [aSHR], 2.74; 95% CI, 1.82-4.12), manifestations of portal hypertension (aSHR, 2.46; 95% CI, 1.45-4.18), age (aSHR, 1.21 per 10 years; 95% CI, 1.03-1.42) and male sex (aSHR, 1.58; 95% CI, 1.04-2.38). In patients without cirrhosis or portal hypertension (n = 8863), the 4-year cumulative incidence of severe withdrawal flares stood at 1.3% (95% CI, 1.0%-1.7%). For those patients with available data confirming adherence to the standard stopping rules (n = 1274), the incidence was 1.1% (95% CI, 0.6%-2.0%).

Conclusions: Severe flares with hepatic decompensation were observed in 1%-2% of patients with CHB after stopping NUC therapy in daily practice. Risk factors included older age, cirrhosis, portal hypertension and male sex. Our findings argue against NUC cessation as part of routine clinical care.