PRECORE MUTANTS OF HEPATITIS-B VIRUS IN PATIENTS RECEIVING IMMUNOSUPPRESSIVE TREATMENT AFTER ORTHOTOPIC LIVER-TRANSPLANTATION

Orthotopic liver transplantation (OLT) is a possible treatment for acu te or chronic liver failure due to hepatitis B virus (HBV) infection, but reinfection of the graft can be a serious complication. The aim of this study was to monitor HBV markers, to analyse pre-core-/core-muta tions as well as to identify the viral population causing reinfection after OLT, and to investigate the emergence or disappearance of these mutants in patients receiving immunosuppressive treatment. Fifty-four pre-and posttransplant serum samples of 17 patients were analysed. All patients underwent OLT for HBV-related liver disease and had HBV-DNA before and after OLT. Total DNA was extracted from all sera and a 240 bp fragment comprising the pre-core region of HBV was amplified by pol ymerase chain reaction (PCR). Precore mutants of HBV were determined b y direct sequencing of these PCR products and by sequencing of PCR clo nes. Eight of 17 patients were infected with pre-core wildtype HBV bef ore OLT (group A). Seven of eight patients of group A were reinfected by precore wildtype HBV after OLT. In one of eight patients in additio n to wildtype HBV a mutant strain (nt. 1899 G --> A) was detected. Nin e of 17 patients were infected with pre-core mutant HBV before OLT (gr oup B). Six of nine patients of group B were reinfected with the same mutant population; in one, an additional pre-core mutation emerged; tw o patients lost pre-core mutant HBV (nt. 1896 and 1899 G --> A). In on e of the latter two, a pre-core start-codon mutant (nt. 1816 G --> T), not detectable before OLT, emerged, in the other a nt. 1897 G --> A s top-codon mutant persisted. Five patients of each group were followed- up for more than 24 (25 to 58) months on immunosuppressive therapy. In all five patients of group A, pre-core wildtype of HBV persisted duri ng long-term follow up. Two of five patients of group B were infected stably with a stop-codon HBV-mutant nt. 1896. In three patients, the n t. 1896 stop-codon mutant disappeared during immunosuppressive therapy . However, in one of the latter three, an HBV stop-codon mutant nt. 18 97 persisted. In conclusion, most patients who underwent OLT for HBV-r elated disease were reinfected with the same virus population that exi sted before OLT. In rare cases, new mutants emerged after OLT or preex isting mutants were lost. During long-term follow-up on immunosuppress ive therapy, in the majority of patients pre-core mutants disappeared a nd wildtype HBV became the predominant virus strain. (C) 1996 Wiley- Liss, Inc.