Pretransplantation pre-S2 and S protein heterogeneity predisposes to hepatitis B virus recurrence after liver transplantation

Abstract Liver transplantation (LT) in patients with hepatitis B virus (HBV) infection often is complicated by recurrence of infection despite immunoglobulin treatment. To evaluate whether variability in HBV genomic sequences and the target of antibody to hepatitis B surface antigen action in pre-LT samples may be associated with a high recurrence rate, HBV pre-S/S regions of 14 HBV-positive candidates for LT (in 9 of these patients, HBV infection subsequently recurred) were amplified and sequenced. Two hundred ninety-one mutations in 1,167 sequenced nucleotides (24.9%) were found. Of these, 120 mutations (10.2%) led to an amino-acid change. The only significant difference between patients with and without recurrent disease was in the number of mutations in the pre-S2 region (total mutations, P = .042; missense mutations, P = .012) of pre-LT HBV DNA. In addition, a difference in amino-acid level was present in the pre-S2 region (P = .030). The delay in HBV infection recurrence was proportional to the number of pre-LT HBV mutations in the pre-S2 and S genes: the higher the number, the longer the interval between LT and recurrence of infection (pre-S2, P = .0124; S, P = .0060; total number of mutations in S protein, P = .0421). In conclusion, pre-LT determination of pre-S/S gene sequence variability showed that heterogeneity of the pre-S2 and, to a lesser extent, S genes was associated with a greater chance for HBV recurrence. Modification of B-cell epitopes of S, but especially of pre-S2, protein leading to conformational changes and alterations in the viral encapsidation and secretion process may facilitate HBV recurrence and contribute to the failure of immune globulin therapy.