Hepatitis B flare: the good, the bad and the ugly

INTRODUCTION: Hepatitis B flare, defined as an event of abrupt ALT elevation to >5x ULN, is a frequent episode during the natural course or during/after antiviral therapy of chronic HBV infection, in both HBeAg-positive and HBeAg-negative patients with chronic hepatitis B or liver cirrhosis. AREAS COVERED: The definition, pathogenesis, clinical presentation, and management of hepatitis B flares in the published literature were reviewed. Hepatitis B flares have been considered as a result of the robust immune response of the patient to an upsurging HBV/HBV-antigen(s). 'Host-dominating flares,' reflect effective immune response, may resolve with ALT normalization and decline of HBV/ antigen(s). Contradictorily, 'virus-dominating flares,' reflect ineffective immune response, are usually followed by persistent/intermittent hepatitis and may even develop hepatic decompensation/failure. EXPERT OPINION: Not all hepatitis B flares require antiviral therapy, and close observation with combined HBsAg/ALT kinetics along the ascending ALT during hepatitis flare may differentiate hepatitis flares for an appropriate treatment/retreatment decision. More studies are needed to verify this proposal. Further immunologic studies using multiple samples during hepatitis B flare are important to clarify the precise underlying mechanisms as the basis for further improvement in the management of hepatitis flare.