S. Gunther et al., ACCUMULATION AND PERSISTENCE OF HEPATITIS-B VIRUS CORE GENE DELETION MUTANTS IN RENAL-TRANSPLANT PATIENTS ARE ASSOCIATED WITH END-STAGE LIVER-DISEASE, Hepatology, 24(4), 1996, pp. 751-758
In renal transplant recipients, chronic hepatitis B virus (HBV) infect
ion often leads to cirrhosis and liver failure. Ln this study, we inve
stigated whether or not in these patients viral variants would emerge
despite immunosuppression, and whether they are associated with a spec
ific course of liver disease. In a population of 552 renal transplant
recipients hepatitis B 24 surface antigen (HBsAg)-positive patients we
re available for a 2-year follow-up. By polymerase chain reaction (PCR
) and DNA sequencing, HBV genomes with deletions in the middle of the
core gene (C-gene) were found in 9 out of the 24 patients. Seven of th
e 9 patients (group I) showed either persistent or increasing amounts
of these variants; all patients had cirrhosis, and 5 died of endstage
Liver disease. The viral variants emerged at least 1 year before liver
failure. In 2 out of the 9 patients, the core deletion variants disap
peared, and no further deterioration of the liver function was observe
d thereafter. In the remaining 15 patients (group II) without deletion
mutants detected at any time, only 3 had cirrhosis (P < .001, group I
vs. II), and none died (P < .001). Between both groups, there were no
statistically significant differences in the other relevant variables
that were examined. These results indicate that HBV C-gene deletion m
utants can accumulate in long-term immunosuppressed patients, and that
their persistence is associated with progressive liver disease. The a
ccumulation of these variants may be caused by the development of cirr
hosis or could be involved in hepatopathogenesis.