Liver and Bile
Gut. 2022;71(8):1629–41
Discontinuation of nucleos(t)ide analogue therapy in HBeAg-negative chronic hepatitis B: A meta-analysis
Background and aims: Sustained virological suppression and hepatitis B surface antigen (HBsAg) loss have been described after nucleos(t)ide analogue (NA) discontinuation for patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). A meta-analysis of the clinical outcomes after NA discontinuation for HBeAg-negative CHB was performed.
Methods: Studies involving NA cessation in HBeAg-negative CHB individuals with a median follow-up of ≥ 12 months were included. Participants were HBeAg-negative at the time of NA initiation. Random-effects meta-analyses were performed for the following clinical outcomes: (1) virological relapse (VR) at 6 and 12 months; (2) clinical relapse (CR) at 6 and 12 months and (3) HBsAg loss. Effect of other variables was estimated using subgroup analysis and meta-regression. Studies including patients stopping entecavir (ETV) and/or tenofovir disoproxil fumarate (TDF) were considered separately to studies including patients stopping older-generation NA.
Results: 37 studies met inclusion criteria. Cumulative incidence of VR and CR after stopping ETV/TDF was 44% and 17% at 6 months and 63% and 35% at 12 months. Similar relapse rates were observed after stopping older NAs. Among patients stopping ETV/TDF, TDF cessation was associated with increased CR rates at 6 months versus ETV. There was an association between follow-up ≥ 4 years and HBsAg loss rates when stopping older NAs. Hepatic decompensation and hepatocellular carcinoma were rare but occurred more frequently in studies including cirrhotic individuals.
Conclusion: Virological relapse is common after nucleos(t)ide analogue (NA) discontinuation, however, clinical relapse was only seen in one-third of patients at 12 months. Stopping NA therapy can be followed by hepatitis B surface antigen clearance, and rates are higher with longer follow-up.