title: Improved clinical outcomes with liver transplantation for hepatitis B-induced chronic liver failure using passive immunization.
abstract: 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 (HBIg) requirements, and identify the relation between viral protein in the liver and clinical reinfection.
  
  
  BACKGROUND
  Liver transplantation is an accepted treatment for end-stage liver disease from chronic HBV infection, although lifelong antiviral treatment (with HBIg 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 stable patients receiving HBIg 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 HBIg to maintain serum HBV surface antibody (HBsAb) levels > or =500 IU/l for the first 6 months after the transplant, and > or =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 HBIg prophylaxis, nine grafts became infected (all 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 HBIg 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 HBIg 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.
authors.affiliation: Department of Surgery and The Charles O. Strickler Transplant Center, University of Virginia, Charlottesville 22906-0005, USA.
authors.forename: R G
authors.initials: RG
authors.lastname: Sawyer
authors.forename: R W
authors.initials: RW
authors.lastname: McGory
authors.forename: M J
authors.initials: MJ
authors.lastname: Gaffey
authors.forename: C C
authors.initials: CC
authors.lastname: McCullough
authors.forename: B L
authors.initials: BL
authors.lastname: Shephard
authors.forename: C W
authors.initials: CW
authors.lastname: Houlgrave
authors.forename: T S
authors.initials: TS
authors.lastname: Ryan
authors.forename: M
authors.initials: M
authors.lastname: Kuhns
authors.forename: A
authors.initials: A
authors.lastname: McNamara
authors.forename: S H
authors.initials: SH
authors.lastname: Caldwell
authors.forename: A
authors.initials: A
authors.lastname: Abdulkareem
authors.forename: T L
authors.initials: TL
authors.lastname: Pruett
mesh_terms: D000328:Adult; D000368:Aged; D002908:Chronic Disease; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006509:Hepatitis B / Q000150:complications* / Q000235:genetics / Q000276:immunology; D006511:Hepatitis B Antigens / Q000097:blood*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood; D006801:Humans; D007116:Immunization, Passive / Q000379:methods*; D017093:Liver Failure / Q000276:immunology / Q000601:surgery* / Q000821:virology*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D004279:DNA, Viral; D006511:Hepatitis B Antigens; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens