Incidence of hepatic decompensation after nucleos(t)ide analogue withdrawal: Results from a large, international, multi-ethnic cohort of patients with chronic hepatitis B (RETRACT-B study)

Despite improvements in the management of chronic hepatitis B (CHB), risk of cirrhosis and hepatocellular carcinoma remains. While hepatitis B surface antigen loss is the optimal endpoint, safe discontinuation of nucleos(t)ide analogue (NA) therapy is controversial due to the possibility of severe or fatal reactivation flares.Multi-center cohort study of virally suppressed, end-of-therapy HBeAg negative CHB patients who stopped NA therapy (n = 1,557). Survival analysis techniques were used to analyze off-therapy rates of hepatic decompensation, and differences by patient characteristics. We also examined a subgroup of non-cirrhotic patients with consolidation therapy of ≥12 months prior to cessation (n = 1,289). Hepatic decompensation was considered related to therapy cessation if diagnosed off-therapy or within 6 months of starting retreatment.Among the total cohort (11.8% diagnosed with cirrhosis, 84.2% start of therapy HBeAg negative), 20 developed hepatic decompensation after NA cessation; 10 events among the subgroup. Cumulative incidence of hepatic decompensation at 60 months off-therapy among the total cohort and the subgroup was 1.8% and 1.1%, respectively. Hepatic decompensation rate was higher among patients with cirrhosis (HR 5.08, P<0.001), and start of therapy HBeAg positive patients (HR 5.23, P<0.001). This association between start of therapy HBeAg status and hepatic decompensation remained significant even among the subgroup (HR 10.5, P<0.001).Patients with cirrhosis and start of therapy HBeAg positive patients should be carefully assessed prior to stopping NAs to prevent hepatic decompensation. Frequent monitoring of viral and host kinetics after cessation is crucial to determine patient outcome.