TY - JOUR T1 - Selection of hepatitis B surface “escape” mutants during passive immune prophylaxis following liver transplantation: potential impact of genetic changes on polymerase protein function JF - Gut JO - Gut SP - 306 LP - 309 DO - 10.1136/gut.45.2.306 VL - 45 IS - 2 AU - P L Shields AU - A Owsianka AU - W F Carman AU - E Boxall AU - S G Hubscher AU - J Shaw AU - K O’Donnell AU - E Elias AU - D J Mutimer Y1 - 1999/08/01 UR - http://gut.bmj.com/content/45/2/306.abstract N2 - CASE REPORT A patient is described who developed hepatitis B virus (HBV) reinfection five months following liver transplantation. Failure of hepatitis B immunoglobulin prophylaxis was associated with the emergence of mutations. HBV gene sequencing identified nucleotide substitutions associated with amino acid changes, one within the major hydrophilic region (MHR) of the HBV surface antigen at amino acid position 144 and one outside the MHR. Because of the overlapping reading frames of surface and polymerase genes, the latter surface antigen change was associated with an amino acid change in the 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 from serum. There was normalisation of liver biochemistry, and liver immunohistochemistry showed a reduction in HBV core and disappearance of HBs antigen staining.CONCLUSION Surface antigen encoding gene mutations associated with HBIg escape may be associated with alteration of the polymerase protein. The polymerase changes may affect sensitivity to antiviral treatment. Selection pressure on one HBV reading frame (for example, HBIg pressure on HBsAg, or nucleoside analogue pressure on polymerase protein) may alter the gene product of the overlapping frame. Such interactions are relevant to strategies employing passive immune prophylaxis and antiviral treatment.HBIghepatitis B immunoglobulinMHRmajor hydrophilic regionPCRpolymerase chain reaction ER -