Possible association of vigorous hepatitis B virus replication with the development of fulminant hepatitis

A 49 year-old man was referred to our hospital for fear of developing fulminant hepatic failure. There had been an outbreak of fulminant hepatitis B in a dialysis clinic in the western part of Honshu, Japan, that resulted in four deaths among six patients. After the sixth patient contracted severe hepatitis, all patients in the unit were screened biweekly for hepatitis B surface antigen (HBsAg) to detect newly infected patients as soon as possible. Our patient was the seventh victim, and on the day he gave a positive result for HBsAg, his hepatitis B virus (HBV) DNA level had reached 1.1 x 10(11) copies/ml as assessed by real time polymerase chain reaction. Sequence analysis of the causal HBV revealed the presence of a mutation in the precore region (nt 1896), two mutations in the core promoter (nt 1762 and nt 1764), and some minor mutations in the P gene that were restricted to the upstream region. These mutations are indicative of a virus with a high replicative rate that cannot secrete HBeAg. Taken together, these findings indicate that it is very likely that the replicative ability of the causal virus was as vigorous as that of HBV in hepatitis B e antigen-positive asymptomatic carriers with markedly high viral titers. The present case report provides clinical evidence of a possible association between the rapid spread of highly replicative HBV before host immunological recognition and the development of fulminant hepatitis.