title: Clinical hepatitis after transplantation of hepatitis C virus-positive kidneys: HLA-DR3 as a risk factor for the development of posttransplant hepatitis.
abstract: BACKGROUND
  Exposure to hepatitis C virus (HCV) and subsequent infection after renal transplantation lead to significant clinical hepatitis in approximately 50% of graft recipients.
  
  
  METHODS
  One hundred thirty-two consecutive renal allotransplant patients, who underwent transplantation of kidneys from HCV-positive cadaveric donors, were studied to investigate the relationship between donor and recipient HLA type and the risk of developing clinical hepatitis. Specific attention was directed toward the DR3 and DR4 alleles, as these had previously been associated with worse prognoses in autoimmune and viral hepatitis.
  
  
  RESULTS
  Overall, 42% of patients receiving kidneys from donors seropositive for HCV developed clinical hepatitis. This was unrelated to preoperative recipient HCV serum reactivity (P=0.65). Patients receiving kidneys from seropositive donors with HCV RNA as detected by PCR were more likely to develop hepatitis than those receiving kidneys from PCR-negative donors (56% vs. 11%; P=0.005). The presence of the DR3 allele was associated with a significant risk of clinical hepatitis (P=0.025); 80% of DR3-positive recipients (n=34) progressed to hepatitis compared with 42% of DR3-negative patients. No other recipient HLA type was significantly related to prognosis. All patients receiving a donated kidney that expressed the B41 allele developed hepatitis, compared with 55% of recipients of non-B41 grafts (P=0.039). No association between the development of clinical hepatitis and HLA compatibility was found.
  
  
  CONCLUSIONS
  These results suggest that both HLA type and viral presence as assayed by polymerase chain reaction, influence the risk of disease progression after transplantation of HCV-positive kidneys. Application of these associations may decrease the relative risk of a recipient contracting HCV hepatitis after cadaveric renal transplantation.
authors.affiliation: Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine, Madison 53792, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Kirk
authors.forename: D M
authors.initials: DM
authors.lastname: Heisey
authors.forename: A M
authors.initials: AM
authors.lastname: D'Alessandro
authors.forename: S J
authors.initials: SJ
authors.lastname: Knechtle
authors.forename: J S
authors.initials: JS
authors.lastname: Odorico
authors.forename: S C
authors.initials: SC
authors.lastname: Rayhill
authors.forename: H W
authors.initials: HW
authors.lastname: Sollinger
authors.forename: J D
authors.initials: JD
authors.lastname: Pirsch
mesh_terms: D000483:Alleles; D015803:HLA-DR3 Antigen / Q000032:analysis; D015804:HLA-DR4 Antigen / Q000032:analysis; D015805:HLA-DR5 Antigen / Q000032:analysis / Q000235:genetics; D016174:Hepacivirus / Q000302:isolation & purification; D006505:Hepatitis / Q000209:etiology*; D006526:Hepatitis C / Q000097:blood* / Q000453:epidemiology; D006801:Humans; D007668:Kidney / Q000382:microbiology*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology*; D012307:Risk Factors
chemical_list: D015803:HLA-DR3 Antigen; D015804:HLA-DR4 Antigen; D015805:HLA-DR5 Antigen