Genetic alterations in the S gene of hepatitis B virus in patients with acute hepatitis B, chronic hepatitis B and hepatitis B liver cirrhosis beforeand after liver transplantation

Background: Several studies have shown that hepatitis B immunoglobulin (HBI G) imposes a selection pressure on the hepatitis B virus (HBV) S gene, and that the emergence of mutations in this region would make reinfection after orthotopic liver transplantation (OLT) possible. Aims. This study was unde rtaken to analyze the presence of HBV S-gene mutations in the different sta ges of HBV infection and the relationship between HBIG therapy and the emer gence of mutations in liver transplant recipients. Methods: The frequency a nd location of mutations in the coding region of the HBV S gene were studie d by PCR and direct sequencing in 30 patients (7 with acute self-limited he patitis B, 16 with chronic hepatitis B and 7 recipients of(OLT) for HBV-rel ated end stage liver disease who became reinfected). Results. The average n umber of amino acid changes was higher in patients with a more advanced sta ge of disease, 0.57 mutations/100 positions in acute hepatitis B and 1.57 i n chronic hepatitis B(1.28 in HBeAg-positive and 1.8 in anti-HBe-positive p atients). The average number of substitutions in the transplanted patients was 2.7 before OLT and 3 after OLT. No amino acid substitutions were detect ed in the "a" determinant of HBsAg in acute hepatitis B, however, 8 substit utions were observed in 6 chronic patients. In 3 OLT patients, 4 substituti ons were observed in samples before and after OLT. One of these patients, w ho had protective levels of anti-HBs, showed 3 additional new amino acid su bstitutions after OLT, suggesting escape mutant selection by the effect of HBIG therapy. No changes were observed between the consensus sequences obta ined several years before and after transplantation, indicating consensus s equence stability. Conclusion. These results show that there is an accumula tion of HBV S-gene mutations in HBV-related end-stage liver disease. Prophy laxis with HBIG mainly obtained from acute self-limited hepatitis patients who have a highly homogeneous viral population, may be one factor underlyin g the reinfection after liver transplantation.