Three cases of severe subfulminant hepatitis in heart-transplanted patients after nosocomial transmission of a mutant hepatitis B virus

Fulminant and severe viral hepatitis are frequently associated with mutant hepatitis B virus (HBV) strains. In this study, the genetic background of a viral strain causing severe subfulminant outcome in heart-transplanted pat ients was studied and compared with viral hepatitis B strains that were not Linked to severe liver disease in the same setting. A total of 46 patients infected nosocomially with HEV genotype A were studied. Five different vir al strains were detected, infecting 3, 9, 5, 24, and 5 patients, respective ly. Only one viral strain was found to be associated with the subfulminant outcome and 3 patient deaths as a consequence of severe liver disease. The remaining 43 patients with posttransplantation HBV infection did not show t his fatal outcome. instead, symptoms of hepatitis were generally mild or cl inically undiagnosed. Comparison of this virus genome with the four other s trains showed an accumulation of mutations in the basic core promoter, a re gion that influences viral replication but also in hepatitis B X protein (H BX) (7 mutant motifs), core (10 mutant motifs), the preS1 region (5 mutant motifs), and the HBpolymerase open reading frame (17 motifs). Some of these variations, such as those in the core region, were located on the tip of t he protruding spike of the viral capsid (codons 60 to 90), also known in pa rt as an important HLA class II-restricted epitope region. These mutations might therefore influence the immune-mediated response. The viral strain ca using subfulminant hepatitis was, in addition, the only strain with a preCo re stop codon mutation and, thus, hepatitis B e antigen (HBeAg) expression was never observed. The combination of these specific viral factors is thou ght to be responsible for the fatal outcome in these immune-suppressed hear t-transplant recipients.