1 Second Academic Department of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece.
Introduction: Long-term, even indefinite treatment with nucleos(t)ide analogs (NAs) is the current first-line therapy for patients with chronic hepatitis B (CHB), regardless of its histological stage. Guidelines and recommendations on duration and endpoints of NA therapy in CHB are not identical and change over time.Areas covered: The authors review NA discontinuation approaches and views with an emphasis on HBeAg-negative patients based on published studies relevant to the topic, stressing on whether or not the optimal endpoint of HBsAg loss is practically achievable.Expert opinion: Discontinuation of NA therapy in HBeAg-negative noncirrhotic patients has to be considered after long-term effective treatment with controlled liver disease activity, undetectable viremia, and significant decline in serum HBsAg titers. Close post-treatment monitoring is required for early intervention in cases of severe clinical relapse. Immediate retreatment hampers the favorable outcome of HBsAg clearance (functional cure) and should be avoided in transient ALT flares. Predictors of such relapses are still under investigation and include viral and patient factors. For HBeAg-positive noncirrhotic patients, there is wide acceptance of the endpoint of HBeAg seroconversion, after a long consolidation period.