Evidence that ursodeoxycholic acid prevents steroid-resistant rejection in adult liver transplantation.
Steroid-resistant rejection continues to be a serious problem in liver transplantation. Since ursodeoxycholic acid (UDCA) is beneficial in several cholestatic disorders and possesses in vitro immunomodulatory and immunosuppressive effects, we have tested in a pilot study the effects of adjuvant UDCA in the prevention of steroid-resistant rejection. Fifty consecutive liver transplant patients were treated with a standard cyclosporine immunosuppressive regimen. Treatment with UDCA (10 mg/kg/d) was initiated in each patient who developed biopsy-proven rejection or biochemical evidence of cholestasis. Clinical and laboratory features were monitored for evidence of rejection. Data were analyzed after at least a 10-month follow-up period was available in each patient. Seven patients died during the study period, all within 4 wk of surgery. No evidence of rejection was documented in these patients. Twenty three of the 43 survivors 53% (23/43) developed an episode of rejection, and UDCA was initiated in each of them. Only one patient had a second episode of rejection, which responded to intravenous methylprednisolone therapy; no patient required antilymphocyte therapy. There was no evidence of toxicity for UDCA. These data suggest that UDCA can be given safely following OLT and may contribute to prevention of steroid-resistant rejection in liver transplant recipients.
Clavien
P A
PA
Department of General and Thoracic Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Sharara
A I
AI
Camargo
C A
CA
Harland
R C
RC
Fitz
J G
JG
D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D002779:Cholestasis / Q000188:drug therapy* / Q000209:etiology; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012008:Recurrence; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid