Selection of hepatitis B surface "escape" mutants during passive immune prophylaxis following liver transplantation: potential impact of genetic changes on polymerase protein function

Case report-A patient is described who developed hepatitis B virus (HBV) re infection five months following liver transplantation. Failure of hepatitis B immunoglobulin prophylaxis was associated with the emergence of mutation s. HBV gene sequencing identified nucleotide substitutions associated with amino acid changes, one within the major hydrophilic region (MHR) of the HB V surface antigen at amino acid position 144 and one outside the MHR. Becau se of the overlapping reading frames of surface and polymerase genes, the l atter surface antigen change was associated with an amino acid change in th e polymerase protein. The patient developed significant allograft hepatitis and was treated with lamivudine (3TC) 100 mg daily. Rapid decline of serum HBV DNA was observed with loss of HBV e antigen and HBV surface antigen fr om serum. There was normalisation of liver biochemistry, and liver immunohi stochemistry showed a reduction in HBV core and disappearance of HBs antige n staining. Conclusion-Surface antigen encoding gene mutations associated with HBIg esc ape may be associated with alteration of the polymerase protein. The polyme rase changes may affect sensitivity to antiviral treatment. Selection press ure on one HBV reading frame (for example, HBIg pressure on HBsAg, or nucle oside analogue pressure on polymerase protein) may alter the gene product o f the overlapping frame. Such interactions are relevant to strategies emplo ying passive immune prophylaxis and antiviral treatment.