MUTATIONS IN THE HEPATITIS-B VIRUS PRECORE CORE GENE AND CORE PROMOTER IN PATIENTS WITH 7 - RECURRENT DISEASE FOLLOWING LIVER-TRANSPLANTATION/

Recurrent hepatitis B virus (HBV) infection is a major problem in pati ents undergoing liver transplantation. Previously, we reported that in fection with HBV strains containing a mutation in the precore region ( G-to-A at nucleotide 1896) was associated with severe recurrent diseas e posttransplantation. In this study we investigated other mutations i n the precore/core gene and core promoter which may be associated with this severe recurrence, The precore/core gene and core promoter of HB V from pre and posttransplantation sera of 15 patients with HBV recurr ence were amplified by polymerase chain reaction (PCR) and sequenced, Pre and posttransplant sequences were very similar for each patient. H BV from patients who developed severe recurrence had significantly mor e mutations in both the nucleotide (P < .05) and predicted amino acid (P < .05) sequences of the precore/core gene, but not in the core prom oter, than virus from patients with mild recurrence, There was also an apparent link between severe disease and HBV strains of genotype D (P < .05), The number of nucleotide and amino acid mutations in the prec ore/core gene was strongly associated with the presence of the precore mutation (P < .01), Mutations were found throughout the entire gene, however, at the amino acid level clustering was observed in the B- and helper T-cell epitopes as well as nuclear localization signals, In th e encapsidation signal, nucleotide mutations were found that were pred icted to increase the stability of the stem-loop structure, Overall, o ur data shows that genotype D and accumulated mutations throughout the HBV precore/core gene, but not core promoter, were associated with se vere recurrent disease posttransplantation. These mutations were stron gly linked to the presence of the precore mutation at nucleotide posit ion 1896 and may contribute to the poor outcome in these patients.