Genotype prevalence, viral load and outcome of hepatitis B virus precore mutant infection in stable patients and in patients after liver transplantation.
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 x 10(6) +/- 60.4 x 10(6) copies/mL. The stable group had a similar origin and HBV genotype prevalence, but a lower mean viral load of 12.4 x 10(6) +/- 29.4 x 10(6) 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.
Ben-Ari
Ziv
Z
Liver Institute and Department of Medicine D, Rabin Medical Center, Sackler School of Medicine, Tel Aviv University, Israel. gbenari@bezeqint.net
Ashur
Yaffa
Y
Daudi
Nili
N
Shmilovitz-Wiess
Hemda
H
Brown
Marius
M
Sulkes
Jaqueline
J
Klein
Athalia
A
Mor
Eytan
E
Tur-Kaspa
Ran
R
Shouval
Daniel
D
D000328:Adult; D018388:Codon, Terminator; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000601:surgery* / Q000821:virology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use; D016031:Liver Transplantation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011184:Postoperative Period; D012008:Recurrence; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016036:Seroepidemiologic Studies; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
D018388:Codon, Terminator; D004279:DNA, Viral; D007166:Immunosuppressive Agents; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine