Antigenic characterisation of pre- and post-liver transplant hepatitis B surface antigen sequences from patients treated with hepatitis B immune globulin

Background/Aims: The success of treatment with hepatitis B hyperimmune glob ulin in preventing recurrence of hepatitis B virus infection in patients un dergoing orthotopic liver transplantation depends on maintaining levels of anti-HBs sufficient to neutralise hepatitis B virus and also on patient com pliance. Breakthrough infections may occur, and these have been associated with the emergence of variants in HBsAg. Methods: Three patients, two who relapsed and one who had no evidence of he patitis B virus infection post-orthotopic liver transplantation were studie d. Polymerase chain reaction and sequencing of pre- and post-orthotopic liv er transplantation samples was followed by antigenic analysis of the in vit ro expressed cloned sequences. Results: In two patients who were treated with hyperimmune globulin, amino acid variation in the region of the immunodominant B cell epitopes of HBsAg occurred. Sequencing of clones revealed fluctuating variant sequences over time. One had clinical relapse and immune escape was evident on in vitro a ntigenic analysis. Patient two lost HBsAg reactivity postorthotopic liver t ransplantation, There was loss of an antigenically critical cysteine molecu le; sequencing of clones revealed that this was the dominant species. The t hird patient relapsed when protective levels of anti-HBs were not maintaine d; HBsAg showed no variation compared to a standard subtype sequence. Conclusion: These data provide strong experimental evidence of immune escap e, It appears that hyperimmune globulin provides the selection pressure. In these patients, HBsAg negativity does not exclude infection of the transpl anted liver.