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 s everal cholestatic disorders and possesses in vitro immunomodulatory a nd immunosuppressive effects, we have tested in a pilot study the effe cts of adjuvant UDCA in the prevention of steroid-resistant rejection. Fifty consecutive liver transplant patients were treated with a stand ard cyclosporine immunosuppressive regimen. Treatment with UDCA (10 mg /kg/d) was initiated in each patient who developed biopsy-proven rejec tion or biochemical evidence of cholestasis. Clinical and laboratory f eatures were monitored for evidence of rejection. Data were analyzed a fter at least a 10-month follow-up period was available in each patien t. Seven patients died during the study period, all within 4 wk of sur gery. No evidence of rejection was documented in these patients. Twent y three of the 43 survivors 53% (23/43) developed an episode of reject ion, and UDCA was initiated in each of them. Only one patient had a se cond episode of rejection, which responded to intravenous methylpredni solone 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.