By Liz Highleyman

Over years or decades, chronic hepatitis B virus (HBV) can progress to severe liver disease including cirrhosis (scarring) and hepatocellular carcinoma (liver cancer).

Effective treatment that lowers HBV viral load can slow or halt liver disease progression, but the sustained effectiveness of therapy is limited by the emergence of drug-resistant virus.

Clearance of hepatitis B surface antigen (HBsAg) and the appearance of antibodies against HBsAg, along with normalization of liver function, is generally accepted as evidence of resolution of or recovery from acute HBV infection.

But HBV reactivation may occur after apparent disease resolution, typically when individuals experience declining immune function -- for example, due to chemotherapy that suppresses the bone marrow. This indicates that people with presumed resolved infection may actually continue to harbor residual "occult" -- or hidden -- virus in their liver.

In a brief report in the September 1, 2008 issue of Clinical Infectious Diseases, Japanese researchers described results from a cross-sectional study of outcomes in individuals who experienced hepatitis B reactivation after previously resolved infection.

HBV reactivation may have various manifestations, they noted as background, ranging from minor subclinical increases in liver enzyme (ALT or AST) levels to rapid and severe potentially fatal fulminant hepatic failure.

In 2005, the investigators sent a questionnaire to 230 hospitals certified by the Japan Society of Hepatology asking about patients who had become newly positive for HBsAg between January 2000 and December 2004. A total of 1239 patients were registered by 93 hospitals. Of these patients, 55 were recorded as having experienced HBV reactivation after resolved infection, while the remaining 1184 were classified as having first-time acute hepatitis B. Then 63 of the 93 hospitals responded to a second survey, providing information on the 552 patients included in the present analysis.

HBV reactivation was defined as a decrease in the level of antibodies to HBsAg associated with the reappearance of HBsAg, a 3-fold elevation of serum ALT above normal, and detection of serum HBV DNA during or after chemotherapy.

Results

"These results revealed that liver-related mortality was significantly higher in the group with HBV reactivation than in the group with acute hepatitis," the study authors concluded. One quarter of these cases developed into fulminant liver failure, and among such patients, mortality was 100%.

Because of these dire outcomes, the study authors recommended that "management of HBV reactivation in patients with resolved HBV infection should be discussed."

"[W]e need to emphasize greater testing of HBV markers, including antibody to hepatitis B core antigen, antibody to HBsAg, and HBV DNA levels before administration of chemotherapy, especially therapy containing rituximab," they wrote. "Patients with resolved HBV infection should be routinely monitored for liver function and HBV DNA levels, and antiviral therapy should be administered immediately when evidence of HBV reactivation is found."

Department of Internal Medicine, Hepatology, and Gastroenterology, Shinshu University School of Medicine, Matsumoto, and Department of Hepatology, Toranomon Hospital, Tokyo, Japan.

9/05/08

Reference
T Umemura, E Tanaka, K Kiyosawa, and others. Mortality secondary to fulminant hepatic failure in patients with prior resolution of hepatitis B virus infection in Japan. Clinical Infectious Diseases 47(5): e52-56. September 1, 2008. (Abstract).