Hepatitis B is a chronic viral infection that may lead to cirrhosis and hepatocellular cancer. During the course of HBV infection, the virus goes through cyclical phases of replication, and nonreplication. Approximately 50% of patients will experience acute reactivations during the natural history of their disease. These reactivations may present as an acute event, may be asymptomatic, and are often spontaneous; these also may occur after cancer chemotherapy or the use of corticosteroid therapy.

HBV reactivation may present as acute hepatitis with symptoms of malaise and fatigue; the average ALT elevation is 300 IU/L but may reach into the thousands. Serum bilirubin may range from mild to marked elevations. Male patients with baseline ALT levels greater than 200 IU/L are three times more likely to develop a reactivation than patients with lower ALT levels. The HBcAb-IgM (the marker for acute hepatitis B) is present in about 60% of patients. Although hepatitis B viral DNA is expected to be present in high concentrations, it may be absent in 50% of patients at the time of peak ALT levels. Reactivation of chronic HBV infection may last weeks to months. A patient's underlying liver disease usually worsens during reactivation, and if cirrhosis is present, decompensation may occur with ascites, variceal bleeding, and liver failure in about 10% with mortality rates of 5%-10%.

Patients with a history of hepatitis B who receive cancer chemotherapy are at risk for HBV reactivation. The virologic and clinical events in these patients offer some insight about the pathogenesis of the disease. The current view is that immunosuppressive drugs favor increased HBV replication while inhibiting cytotoxic T cell function in the liver. When the cycle of chemotherapy is completed, the reconstituted immune system recognizes enhanced HBV antigen expression on the hepatocyte membrane leading to cell necrosis, which can sometimes be massive. About 50% of HBsAg positive patients, and as many as 6% of HBsAg negative but core positive (HBcAb) patients undergoing chemotherapy, may have experienced such a reactivation.

Corticosteroid therapy should be avoided in patients with chronic hepatitis B except as a life-saving treatment. HBV reactivation following cancer chemotherapy is managed by continuing corticosteroid therapy between courses and by very slow tapering of the dose, while monitoring ALT and HBV DNA levels during steroid withdrawal, which may last several months.

The treatment of spontaneous reactivation is not well defined. Interferon is not considered a useful treatment and is not recommended in patients who deteriorate during a reactivation. Lamivudine (3TC, Epivir) is an attractive choice because of its potent suppression of HBV replication. Since viral replication resumes within three months of discontinuing lamivudine in most patients, one is committed to long-term treatment once drug therapy starts. The role of other drugs such as Famciclovir (Famvir) needs to be defined.