-
[show abstract]
[hide abstract]
ABSTRACT: Although lamivudine (LAM) is a potent inhibitor of hepatitis B virus (HBV), prolonged therapy may induce the development of LAM-resistant strains, YMDD mutants. Although YMDD mutants have impaired replication that leads to a benign clinical course compared with wild-type virus, some immunosuppressive agents may enhance replication of YMDD mutants, causing a severe hepatitis flare. We retrospectively investigated the incidence and clinical outcomes of YMDD mutants in renal allograft recipients on immunosuppressive treatment. Clinical records of 25 renal allograft recipients, who underwent renal transplantation between December 1997 and February 2006 were hepatitis B surface antigen positive at the time of transplantation, were reviewed. All patients received LAM treatment after renal transplantation. Over 9 to 98 months of follow-up, 16 patients (64.0%) maintained undetectable HBV DNA levels; however, 9 patients (36.0%) showed persistent or increased levels of HBV DNA. Seven were identified as having developed YMDD mutants. Although genotypic analysis was not performed, YMDD mutants were strongly suspected in another two patients, who developed severe hepatic dysfunction combined with high levels of HBV viremia at close to 2 years of LAM therapy. One patient recovered after hepatic transplantation and another patient died of hepatic failure. In conclusion, the incidence of YMDD mutants was similar to that of nonimmunosuppressed individuals; however, the presence of these mutants made it more likely for severe liver disease to develop in renal transplant recipients. Therefore, close monitoring for the development of YMDD mutants should be performed during LAM treatment, especially in this group of patients.
Transplantation Proceedings 01/2008; 39(10):3121-6. · 1.00 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We investigated the overall and site-specific prevalence of pre-S mutations and its clinical significance in patients with genotype C hepatitis B virus (HBV) infection. Three hundred subjects were included: 50 asymptomatic carriers (AC), 87 chronic hepatitis (CH), 91 liver cirrhosis (LC) and 72 hepatocellular carcinoma (HCC). Pre-S mutations were determined by nucleotide sequence analysis. Possible correlations between pre-S mutations and clinical/virological parameters were examined. Pre-S mutations were detected in 82 cases (27.3%); it was more frequently found in HCC (43.1%) and LC (35.2%) group than in the CH (20.7%) and AC (2.0%) group. Pre-S2 deletion was the most commonly found mutation (10.7%), followed by pre-S2 start codon mutation (9.7%), pre-S1-S2 deletion (3.0%) and both pre-S2 deletion and start codon mutation (2.7%). Pre-S2 deletion and pre-S2 start codon mutation were more frequently detected in advanced diseases (LC and HCC). Pre-S mutations were associated with older age and higher rates of positive HBV DNA (>/=0.5 pg/mL). Advanced disease and positive HBV DNA were shown to be independent predictors of pre-S mutations by logistic regression analysis. These findings suggest that pre-S mutations, especially pre-S2 deletions and pre-S2 start codon mutations, are common in patients with genotype C HBV infection and are associated with advanced liver disease and active viral replication.
Journal of Viral Hepatitis 03/2007; 14(3):161-8. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Renal recipients with hepatitis B virus (HBV) should be treated with prolonged lamivudine. However, lamivudine resistance usually results after YMDD mutation within the HBV polymerase gene. Thereupon, the aim of this study was to investigate the genotypic resistance to lamivudine among renal transplant recipients to identify its effect on the clinical course of HBV in these patients. Between March 1997 and September 2003, eight of 17 renal transplant patients with hepatitis B virus were enrolled into this study and treated with 100 mg of lamivudine once each day. We amplified a selected region of the polymerase gene of HBV in order to confirm mutations in the YMDD motif. Mutations of YMDD region were observed in five of eight patients (62.5%). Out of five patients positive for HBV DNA, three (60%) showed genotypic resistance (YMDD mutation) with a normal ALT level. Two patients converted to HBV DNA negative. But, they were not associated with HBeAg seroconversion. Out of three patients who were pretransplant HBV DNA negative, genotypic resistance was observed in two patients (67%) revealing both positivity of HBe antibody and negativity of HBV DNA. In conclusion, although a normal ALT level and HBV DNA negative are maintained, the mutation of the YMDD locus may develop. Accordingly, we suggest that if the YMDD mutation is not involved in the progression of hepatitis B, lamivudine therapy should be continued despite genotypic resistance.
Transplantation Proceedings 04/2005; 37(2):1235-7. · 1.00 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A novel parvovirus was identified in Manchurian chipmunks inhabiting Korea. Hepatitis B surface antigen (HBsAg) was detected in sera from 4 animals among 62 apparently healthy chipmunks. Electron microscopic examination of the HBsAg-positive sera revealed virus-like spherical particles 20-22 nm in diameter. Extraction of nucleic acid under annealing conditions from the serum samples containing virus-like particles yielded a single species of DNA molecule with the electrophoretic mobility of 5.6-kb double-stranded DNA. Four overlapping clones that encompassed almost the full-length viral genome, except both ends, were obtained. By sequencing these clones, we determined the sequence of 5097 nucleotides of the viral DNA. Two open reading frames were identified, with the left side open reading frame encoding a putative nonstructural protein and the right side open reading frame encoding a putative capsid protein. The nucleotide and amino acid sequences showed significant homology to parvovirus B19 and simian parvovirus, but showed little homology to other mammalian autonomous parvoviruses or adeno-associated viruses. These observations indicate that the virus isolated from Manchurian chipmunks is a novel parvovirus and may be a potentially useful animal model of human B19 infection as a new member of the Erythrovirus genus of the Parvoviridae.
Virology 02/1999; 253(2):250-8. · 3.35 Impact Factor
