Improved clinical outcomes with liver transplantation for hepatitis B-induced chronic liver failure using passive immunization

Objective The goals were to summarize the results of liver transplantation for chronic hepatitis B disease (HBV) at the University of Virginia, correlate pretransplant viral markers with posttransplant hepatitis B immunoglobulin (HBlg) requirements, and identify the relation between viral protein in the liver and clinical reinfection. Summary Background Data Liver transplantation is an accepted treatment for end-stage liver disease from chronic HBV infection, although lifelong antiviral treatment (with HBlg or antiviral agents) is still necessary. Patients with evidence of active viral replication (detectable serum HBV-DNA or e antigen) at the time of transplant have a higher rate of allograft infection. Whether clinically sta bie patients receiving HBlg immunoprophylaxis have detectable viral products in their grafts remains unknown. Methods Forty-four transplants performed for HBV disease at the University of Virginia since March 1990 were reviewed. Most patients underwent aggressive passive immunoprophylaxis with HBlg to maintain serum HBV surface antibody (HBsAb) levels greater than or equal to 500 IU/l for the first 6 months after the transplant, and greater than or equal to 150 IU/l thereafter. Patients had viral markers quantified, underwent pharmacokinetic analysis of HBsAb levels to adjust: dosing, and were biopsied routinely every 3 to 6 months and when indicated. Results Forty-four transplants were performed in 39 patients. Actual 1-year and 3-year graft survival was 95% and 81%, respectively, and 1-year and 3-year patient survival was 98% and 96%, respectively. After the adoption of indefinite HBlg prophylaxis, nine grafts became infected tail in recipients positive for HBV e antigen). Three occurred within 8 weeks of transplantation and were associated with a short HBsAb half-life and a wild-type virus. Six occurred >8 months after the transplant, and most of these were associated with viral mutation. Quantification of pretransplant markers was an overall poor predictor of HBlg requirements after the transplant. Immunohistochemistry demonstrated transient low-level expression of core protein in the liver in 23% of patients without serum or clinical evidence of recurrent hepatitis. Conclusions An excellent outcome is possible after liver transplantation for chronic HBV disease using HBlg dosed by pharmacokinetic parameters. Currently, quantification of pretransplant serum markers of the HBV antigen load does not predict the intensity of posttransplant treatment required for good clinical outcomes. Because HBV is not eradicated from the patient, some form of indefinite antiviral therapy continues to be warranted.