title: Significance of early aminotransferase elevation after liver transplantation.
abstract: BACKGROUND
  We retrospectively reviewed 213 consecutive patients who received their first liver allograft between January 1 and December 31, 1993, in order to study the impact of ischemia/preservation/reperfusion injury (IPRI) on patient and graft outcome.
  
  
  METHODS
  The extent of IPRI was assessed by the peak value of aspartate aminotransferase (ASTmax) observed within the first 72 hr after transplant. For the purpose of univariate analysis, categorical classification of recipients was done based upon ASTmax as follows: group 1, ASTmax<600 U/L (n=46); group 2, ASTmax=600-2000 U/L (n=97); group 3, ASTmax>2000-5000 U/L (n=50), and group 4, ASTmax>5000 U/L (n=17). For multivariate analysis, stepwise Cox regression was performed with age, ASTmax, and United Network for Organ Sharing (UNOS) status as covariates.
  
  
  RESULTS
  Groups were comparable with respect to age, UNOS status at the time of transplantation, and diagnostic case mix. Median follow-up was 644 days. The overall incidence of primary graft nonfunction (PNF) was 7.6%. PNF incidence was significantly correlated with the severity of IPRI (0%, 4%, 10%, and 41% for groups 1 to 4, respectively, P < 0.0001), but this impact was confined to the respective rates of retransplantation as early patient survival was unaffected. The 1-year survival of patients whose initial grafts manifested extreme IPRI (group 4) was significantly inferior to recipients in the three other groups (77%, 71%, 73%, and 52% for groups 1 to 4, respectively, P=0.03). This increased mortality was confined to patients who never achieved discharge from their initial hospitalization, with no significant differences between groups being detected in the survival of those patients who were discharged (84%, 80%, 85%, and 81% for groups 1 to 4, respectively, P=NS). Although overall 1-year graft survival was strongly correlated with the extent of IPRI (77%, 67%, 62%, and 41% for groups 1 to 4, respectively, P=0.001), this correlation was abolished when survival of grafts not lost to PNF was examined at 1 and 2 years. Stepwise Cox regression analysis confirmed the independent association between ASTmax and patient and graft survival. The long-term quality of allograft function as well as the incidence of chronic rejection and biliary complications were unrelated to the extent of IPRI.
  
  
  CONCLUSIONS
  We conclude that: (1) patient survival is influenced by IPRI only when it is extreme (ASTmax>5000 U/L), provided parameters of graft function are used in conjunction with aminotransferase values to assess the need for prompt retransplantation; (2) short-term graft survival is proportional to the extent of IPRI, but grafts that are not lost to PNF have equivalent 1- and 2-year survival irrespective of the magnitude of IPRI; (3) 40% of grafts with extreme IPRI are lost to PNF, but the same proportion also provide long-term function; and (4) for surviving grafts, long-term biochemical function as well as the incidence of biliary complications and of chronic rejection are unrelated to the extent of IPRI.
authors.affiliation: Department of Surgery, UCLA School of Medicine and Dumont-UCLA Transplant Center, Los Angeles, California 90095, USA.
authors.forename: H R
authors.initials: HR
authors.lastname: Rosen
authors.forename: P
authors.initials: P
authors.lastname: Martin
authors.forename: J
authors.initials: J
authors.lastname: Goss
authors.forename: J
authors.initials: J
authors.lastname: Donovan
authors.forename: J
authors.initials: J
authors.lastname: Melinek
authors.forename: S
authors.initials: S
authors.lastname: Rudich
authors.forename: D K
authors.initials: DK
authors.lastname: Imagawa
authors.forename: M
authors.initials: M
authors.lastname: Kinkhabwala
authors.forename: P
authors.initials: P
authors.lastname: Seu
authors.forename: R W
authors.initials: RW
authors.lastname: Busuttil
authors.forename: C R
authors.initials: CR
authors.lastname: Shackleton
mesh_terms: D000328:Adult; D001219:Aspartate Aminotransferases / Q000378:metabolism*; D001659:Biliary Tract / Q000503:physiopathology; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008099:Liver / Q000201:enzymology; D016031:Liver Transplantation / Q000502:physiology; D008297:Male; D016853:Muromonab-CD3 / Q000627:therapeutic use; D012189:Retrospective Studies; D016559:Tacrolimus / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D016572:Cyclosporine; D001219:Aspartate Aminotransferases; D016559:Tacrolimus