HEPATITIS-B VIRUS SEQUENCE CHANGES EVOLVING IN LIVER-TRANSPLANT RECIPIENTS WITH FULMINANT-HEPATITIS

Background/Aims: Patients undergoing liver transplantation for hepatit is B virus (HBV) related liver cirrhosis are at major risk of developi ng HBV recurrence, and occasionally fulminant hepatitis, Here we teste d in a longitudinal study whether specific viral variants are associat ed with fulminant HBV infection in the graft, Methods: The complete HB V genomes isolated from the sera of three patients with HBV and HBV an d hepatitis delta virus (HDV) coinfection during chronic infection bef ore and during fulminant reinfection after transplantation were amplif ied and directly sequenced, Results: Twenty, 25 and 19 mutations, dist ributed over the entire genome, were identified which differed between the HBV genomes isolated from each patient during chronic and fulmina nt infection, respectively This reflects a much higher rate of nucleot ide sequence changes than expected from the natural variation of HEX N o common HBV mutation emerged in any of the three cases during fulmina nt infection, However, precore defective viruses were found to be pres ent in all three patients at the time of fulminant infection and in tw o of the patients before fulminant infection, Two of the patients had preS2-defective HBVs both before and after transplantation. A point mu tation in the 'a'-determinant of the surface protein emerged in one ca se after transplantation under treatment with polyclonal HBV specific immunoglobulins, Conclusions: Many new, but no specific common mutatio ns emerged during fulminant HBV reinfection, Although HBeAg defective variants were found in all cases studied, the presence of these varian ts also during chronic infection in two cases demonstrates that they a re not sufficient to cause fulminant hepatitis, Thus, other factors th an the emergence of a specific viral strain seem to contribute to the development of fulminant reinfection in a liver graft.