[A study on mutations of the overlapping hepatitis B virus surface and polymerase gene in patients with HBV reinfection after liver transplantations].
OBJECTIVE
To investigate the influence of combined hepatitis B immune globulin (HBIG) and lamivudine (LMV) treatment on hepatitis B virus (HBV) surface antigen and polymerase overlapping gene mutations in HBV reinfected liver transplant recipients.


METHODS
From June 2002 to December 2003, 320 patients who underwent liver transplantations due to HBV-related end-stage liver diseases were followed-up for 1.5 to 3 years postoperatively. Fourteen patients developed HBV reinfection. They had LMV before their liver transplantations and had LMV and HBIG after the transplantations to prevent HBV infections. Their serum levels of HBV DNA were measured by polymerase chain reaction. Gene sequencing method was used to analyze HBV genotype and mutations of the S gene. Micro-particle enzyme immunoassay was used to measure the serum concentration of HBIG.


RESULTS
(1) There was no obvious difference in the number of amino acid mutation sites in S and P regions before and after the transplantations. (2) The HBV genotypes were B-type (n=2) and C-type (n=12) in the reinfected group before the transplantations, and genotypes after the transplantations remained the same. (3) HBIG concentrations were 0 U/L in 7 patients, less than 100 U/L in 5 patients, and more than 100 U/L in 2 patients. Mutations were detected as I126S, T131N, S143T and G145R in 'a' determinant and L110F, I113S, T160K in up- or down-stream of 'a' determinant. (4) Mutations in S gene caused missense mutation in the surface antigen region. These mutations also caused corresponding missense mutations in the polymerase region. The missense mutation in the polymerase region involved lamivudine mutation sites and other mutation sites.


CONCLUSIONS
Immunosuppressant therapy has no obvious influence on the numbers of mutations, but it can influence the sites of the mutations. Besides 'a' determinant mutations, there exist mutations in up- or down-streams of 'a' determinant and they may cause HBV reinfection.
Song
Hong-li
HL
Center of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, China.
Shen
Zhong-yang
ZY
Wang
Jian
J
Zheng
Wei-ping
WP
Wang
Zheng-lu
ZL
D000328:Adult; D005260:Female; D005787:Gene Frequency; D016679:Genome, Viral; D005838:Genotype; D006509:Hepatitis B / Q000188:drug therapy / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D007136:Immunoglobulins / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009154:Mutation; D032041:Nested Genes; D012008:Recurrence
D006514:Hepatitis B Surface Antigens; D007136:Immunoglobulins; D019259:Lamivudine; C045213:hepatitis B hyperimmune globulin