Residual hepatitis B virus particles in liver transplant recipients receiving lamivudine: PCR quantitation of HBV DNA and ELISA of preS1 antigen

Abstract

Lamivudine, an antiviral agent, has a potential role in the treatment of recurrent or acquired de novo hepatitis B virus (HBV) infection after liver transplantation. During lamivudine therapy, residual HBV particles in serum, PBMC, and liver were quantified in 7 patients in whom hepatitis B occurred de novo (n = 4) or recurred (n = 3). HBV DNA and preS1 antigen were measured using a sensitive PCR technique and an in-house ELISA method, respectively. The genetic and antigenic properties of HBV variants that emerged during lamivudine treatment were also examined. One month after the outset of lamivudine treatment, all 7 patients remained positive for both HBV DNA and preS1 antigen in serum, reflecting residual HBV replication. At the end of therapy, four patients were considered to be lamivudine responders, including one who seroconverted to anti-HBs but remained HBV DNA positive in the liver (> 10(3) copies/microg of DNA). Among the three patients who did not respond to lamivudine, one had pol mutations (L450P and S550C) that had not been described previously, in addition to the common mutations within the YMDD locus and B domain. Defective core and preS viral proteins and atypical sedimentation profiles of HBV DNA-positive particles were observed in all three lamivudine-resistant patients. These findings confirm the persistence of HBV in liver transplant recipients despite strong inhibition of replication by lamivudine, and show abnormal viral transcription and/or morphogenesis in lamivudine-resistant patients.