CLINICAL AND MOLECULAR VIROLOGICAL DIFFERENCES BETWEEN FULMINANT HEPATIC FAILURES FOLLOWING ACUTE AND CHRONIC INFECTION WITH HEPATITIS-B VIRUS

Clinical and molecular biological characteristics were compared betwee n patients who presented with fulminant hepatic failure following acut e infection with hepatitis B virus (HBV) and those who developed hepat ic failure during they carried HBV. The 11 patients with acute HBV inf ection had higher levels of alanine aminotransferase (mean +/- SD: 494 3 +/- 2867 vs. 1157 +/- 678 IU/L, P < 0.01), more often with a single peak (91% vs. 0%, P < 0.001), and lower total bilirubin levels (15.3 /- 4.4 vs. 28.1 +/- 14.3 mg/100 mi, P < 0.01) than the 13 patients wit h chronic HBV infection. Hepatitis B surface antigen was detected less often (55% vs. 100%, P < 0.05) and viral DNA polymerase less frequent ly (0% vs. 46%, P < 0.05) in the patients with acute than chronic HBV infection. Hepatitis B e antigen was detected in one (9%) patient with acute infection, less frequently than in six (46%) patients with chro nic infection (P < 0.05). Mutations in the precore region was detected in HBV DNA clones from ten (91%) patients with acute infection and on ly in those from eight (62%) patients with chronic infection. All HBV DNA clones from the five (38%) patients with chronic infection that di d not have precore mutations, however, possessed mutations in the core promoter. These results indicate that HBV mutants incapable of transl ating hepatitis B e antigen would play a major role in fulminant hepat ic failure occurring after acute HBV infection. In contrast, HBV varia nts with core promoter mutations for reducing the transcription of hep atitis B e antigen would play an additional role in fulminant hepatic failure developing during chronic infection. (C) 1998 Wiley-Liss, Inc.