Flares on and off therapy during chronic HBV infection: Pathogenesis, significance and management

Approximately 400 million people worldwide are chronically infected with the hepatitis B virus (HBV). Chronic infection with HBV can lead to progressive liver diseases including cirrhosis, liver failure, and hepatocellular carcinoma. During treatment of chronic hepatitis B (CHB) patients, flares of inflammatory activity are a well known phenomenon. Flares can be life threatening but have also been associated with virological response. While, interferon induced flares have been attributed to the stimulatory effect of IFN, and may precede HBeAg seroconversion, Lamivudine related flares are seen during treatment and after withdrawal of lamivudine, which are probably caused by reoccurrence of HBV replication, and have been associated with decompensation of liver disease. These flares play an important role in the treatment with Peg-IFN α-2b alone or in combination with lamivudine, and patients with pre-existing cirrhosis are at greater risk for experiencing a flare. Furthermore, host induced flares but not virus induced flares may herald a response to therapy. For optimisation of treatment, it is necessary to understand the virological and immunological mechanisms which induce the specific flare patterns. This article reviews the pathogenesis, significance and management of flares encountered during and after cessation of treatment of patients with chronic HBV infection.