Genotype prevalence, viral load and outcome of hepatitis B virus precore mutant infection in stable patients and in patients after liver transplantation

Ziv Ben-Ari, Yaffa Ashur, Nili Daudi, Hemda Shmilovitz-Wiess, Marius Brown, Jacqueline Sulkes, Athalia Klein, Eytan Mor, Ran Tur-Kaspa, Daniel Shouval

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: The precore mutant is detectable in most Israeli patients with persistent hepatitis B virus (HBV) infection. The aim of this study was to determine the prevalence of HBV genotypes, viral load and outcome of precore mutant infection in stable patients and in patients after liver transplantation. Methods: The prevalence of HBV genotype and viral load were investigated in 81 patients with HBV precore mutant infection. Of these, 50 patients (40 males, 10 females; mean age 43.4 ± 11.0 yr) underwent liver transplantation and were serum HBV DNA-negative by hybridization at the time of transplantation. Patients received long-term HBV immunoprophylaxis and immunosuppression, and lamivudine in cases of graft HBV recurrence. The remaining 31 patients were stable, with serum anti-HBe-positivity. Genotypes were tested by restriction fragment length polymorphism of an S gene amplicon. Precore mutations were studied with an INNO-LiPA probe assay. Results: Follow-up was 46.6 ± 37.7 months. Most of the transplanted group was of Middle Eastern origin (53.6%); the remainder were from Eastern Europe (21.4%), Western Europe and the USA (10.8%), Africa (7.1 %), and Asia (7.1 %). In the transplanted group, the pre-transplant HBV genotype D was the most prevalent (96%), while genotype A was found in only 4%. Eleven patients (22%) developed recurrent HBV infection post-transplantation. There were no differences in genotype distribution between patients with graft reinfection or lamivudine resistance and patients without recurrence. Mean viral load at recurrence was 148.4 × 106 ± 60.4 × 106 copies/mL. The stable group had a similar origin and HBV genotype prevalence, but a lower mean viral load of 12.4 × 106 ± 29.4 × 106 copies/mL (p = 0.007). The prevalence of mutations at the precore region and codon 28 was similar in both groups. Conclusions: The chronic precore mutant HBV-infected patients were characterized as follows: (i) genotype D was the most frequent genotype, (ii) the HBV genotype distribution was similar in patients with stable infection and after liver transplantation, (iii) viral load at recurrence was significantly higher than in stable infection, and (iv) HBV genotype was unrelated to the development of recurrence or lamivudine resistance in the tested population.

Original languageEnglish
Pages (from-to)415-422
Number of pages8
JournalClinical Transplantation
Volume18
Issue number4
DOIs
StatePublished - Aug 2004

Keywords

  • Genotype
  • Hepatitis B
  • Liver transplantation
  • Precore mutant
  • Viral load

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