Occult hepatitis B virus infection and lamivudine-resistant mutations in isolates from renal patients undergoing hemodialysis.
OBJECTIVE
Patients undergoing hemodialysis are at risk of infection with both hepatitis B virus (HBV) and hepatitis C virus (HCV). Occult HBV infection is usually associated with low levels of HBV and is frequently detected in HCV-infected patients. The aims of the present study were to compare the prevalence of occult HBV infection among anti-HCV-positive and anti-HCV-negative patients undergoing hemodialysis, and characterize the molecular patterns of HBV isolates from patients with occult infection.


METHODS
Serum samples from 100 patients negative for hepatitis B surface antigen undergoing hemodialysis, half of whom were positive for anti-HCV antibodies, were tested for the presence of HBV-DNA using semi-nested polymerase chain reaction (PCR). PCR products of the S gene were directly sequenced.


RESULTS
HBV-DNA was detected in 15 samples. There were no significant differences in HCV status, sex, age, time of dialysis, alanine aminotransferase levels or HBV serological markers between patients with or without occult HBV infection, with the exception of antibody to hepatitis B core antigen (anti-HBc)-only serological marker (P = 0.003). All six HBV isolates that could be sequenced were of genotype A/subgenotype A1. Four of these six HBV isolates contained mutations associated with lamivudine resistance in the DNA polymerase (two with L180M/M204V and two with rt173V/180M/204V) and a specific substitution (Y100C) in the HBV small surface protein.


CONCLUSIONS
HBV isolates with the identified substitutions have the potential to spread silently by nosocomial transmission within the hemodialysis unit. These results have potential implications for the management of patients with occult HBV infection undergoing hemodialysis.
Motta
Jorge S
JS
Molecular Virology Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil.
Mello
Francisco C
FC
Lago
Barbara V
BV
Perez
Renata M
RM
Gomes
Selma A
SA
Figueiredo
Fatima F
FF
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D001938:Brazil / Q000453:epidemiology; D003428:Cross Infection / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000635:transmission; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015684:Gene Products, pol / Q000235:genetics; D005838:Genotype; D006509:Hepatitis B / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology / Q000635:transmission; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D015995:Prevalence; D006435:Renal Dialysis; D014759:Viral Envelope Proteins / Q000235:genetics
D000998:Antiviral Agents; D004279:DNA, Viral; D015684:Gene Products, pol; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D018937:Hepatitis C Antibodies; C066027:P protein, Hepatitis B virus; C118669:S envelope protein, hepatitis B virus; D014759:Viral Envelope Proteins; D019259:Lamivudine