Hepatitis B Flare After Cessation of Nucleos(t)ide Analogue Therapy in HBeAg-Negative Chronic Hepatitis B: To Retreat or Not to Retreat.

Abstract

Finite nucleos(t)ide analogue (Nuc) therapy in HBV suppressed hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B may substantially increase hepatitis B surface antigen (HBsAg) loss rate after cessation of therapy, in which "no retreatment" is a strong predictor for HBsAg loss. However, the main safety concern of no retreatment is hepatitis flare leading to hepatic decompensation or even fatality. Hence it is crucial to make retreatment decision that is not too soon to allow sufficient immune clearance facilitating further HBsAg decline towards HBsAg loss and, more importantly, not too late to prevent adverse outcomes. This review discussed and evaluated the presentations and pathogenesis of hepatitis B flare, with emphasis on issues surrounding off-Nuc hepatitis B flare in HBeAg-negative patients. The advantage and deficiency of retreatment decision based on current biochemical marker(s) alone were reviewed. The concept of immune clearance and its clinical application of combined HBsAg/ALT kinetics during hepatitis flare in the differentiation between two types of hepatitis flare were also reviewed. The utility of combined HBsAg/ALT kinetics for retreatment decision was proposed and elaborated in detail. The feasibility, application and underlying pathobiologic mechanism(s) of this approach require further investigation. Studies on the role of immunologic and/or other viral markers in retreatment decision are also needed. In conclusion, combined qHBsAg/ALT kinetics seems to be better than current biochemical marker(s) alone in the differentiation of types of hepatitis flare for better decision that retreatment is not necessary or not too soon for "host-dominating flare" to allow sufficient immune clearance response facilitating further HBsAg decline towards HBsAg loss, and not too late for "virus-dominating flare", to prevent adverse outcome such as hepatic decompensation.