title: Hepatitis flares and hepatitis B e antigen seroconversion: implication in anti-hepatitis B virus therapy.
abstract: Hepatitis flares or acute exacerbations, defined as an abrupt elevation of serum alanine aminotransferase (ALT) over fivefold the upper limit of normal (ULN), of chronic hepatitis B virus (HBV) infection are the results of HLA-I restricted, cytotoxic T lymphocyte (CTL)-mediated immune response against HBV and its downstream mechanisms. Higher ALT levels reflect a more vigorous immune response and a more extensive hepatolysis that, in the extreme situation, may lead to decompensation and failure. In contrast, higher ALT also reflects a more robust immune clearance of HBV and, therefore, a higher chance of HBV-DNA loss and hepatitis B e antigen (HBeAg) seroconversion, both in the setting of natural course and drug therapy. Alanine aminotransferase of fivefold the ULN appears to be a significant cut-off level to categorize the patients in terms of endogenous immune response against HBV. Patients with ALT levels less than fivefold the ULN or those with a less vigorous immune response require immunomodulation to induce robust immune response to enhance HBV clearance. In contrast, those with a more vigorous immune response or those with ALT flare over fivefold the ULN should be monitored closely for spontaneous HBV clearance/HBeAg seroconversion or to start direct antiviral therapy in time to prevent the occurrence or deterioration of hepatic decompensation. In conclusion, a better understanding of the pathogenetic mechanisms and natural course of hepatitis flares, wiser selection of patients and the timing of drug therapy are crucial to achieve better treatment results.
authors.affiliation: Liver Research Unit, Medical College, Chang Gung University, Taipei, Taiwan. liveryfl@so-net.net.tw
authors.forename: Yun-Fan
authors.initials: YF
authors.lastname: Liaw
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000276:immunology / Q000627:therapeutic use; D006510:Hepatitis B Antibodies / Q000276:immunology / Q000627:therapeutic use; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000097:blood / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D006801:Humans
chemical_list: D000998:Antiviral Agents; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase