Nucleos(t)ide Analog Treatment Discontinuation in Chronic Hepatitis B Virus Infection: A Systematic Literature Review.

Background and Aims: The aim of this systematic literature review (SLR) was to examine outcomes and associated predictors following nucleos(t)ide analog (NA) treatment cessation in adult patients with chronic hepatitis B virus infection. Methods: The SLR was conducted according to PRISMA methodology. All included studies were quality assessed using appropriate scales or checklists. Results: The SLR identified 145 studies. Cumulative rates of clinical relapse (40 studies), virological relapse (53 studies), biochemical relapse (10 studies) and retreatment events (14 studies) post NA cessation varied widely across studies (clinical relapse: 40%-65%, virological relapse: 75%-94%, biochemical relapse: 63%-73%, retreatment rates: 30%-78% at 24 and 144 weeks, respectively). Significant predictors with adequate evidence of clinical relapse included older age, male gender, and higher hepatitis B surface antigen (HBsAg) and hepatitis B virus DNA at baseline and end of treatment. HBsAg loss was reported in 25 studies, with overall median HBsAg loss rates ranging from 2% at 24 weeks (5 studies) to 11% at 192 weeks (2 studies) post NA cessation. There was adequate evidence for lower HBsAg level at baseline and end of treatment as a significant and consistent predictor of HBsAg loss. Conclusion: There is considerable heterogeneity among studies of NA cessation. Data are currently incomplete to provide strong recommendations for NA cessation or to identify patients who may benefit most from this approach in clinical practice. Further studies are required to provide clearer guidelines, and tools to assess and monitor patients who may benefit from NA treatment cessation.