A randomized clinical trial of ursodeoxycholic acid as adjuvant treatment to prevent liver transplant rejection.
Acute rejection following orthotopic liver transplantation is a common problem despite current immunosuppressive regimens. Ursodeoxycholic acid (UDCA) has been shown in small, open-labeled studies to prevent rejection episodes, although its effects on complications such as infections, length of hospital stay, and survival have not been evaluated. We conducted a randomized, placebo-controlled, double-blind trial to determine if UDCA (10-15 mg/kg/d) added to a cyclosporine-based immunosuppressive regimen was associated with a decrease in the incidence of at least one episode of acute cellular rejection. Secondary end-points included determining differences in the total number of rejection episodes, the use of muromonab-CD3, the incidence of infections, length of hospital stay, and survival at 90 days and 1 year. Fifty-two patients were randomized, 28 to the treatment group and 24 to the placebo group. During the 3 months of the trial, there was no difference between the placebo and UDCA groups in the number of patients who were rejection-free; however, there were significantly fewer patients in the treatment group who had multiple episodes of acute rejection (0 vs. 6; P = .007). Patients in the treatment group experienced a significantly lower incidence of bacterial infections (4% vs. 29%; P = .02), shorter hospital stay (25 days vs. 34 days; P = .03), and better 90-day survival (100% vs. 83%; P = .04) and 1-year survival (93% vs. 79%). The addition of UDCA to a cyclosporine-based immunosuppressive regimen results in significantly fewer patients experiencing multiple episodes of rejection and improved survival at 90 days and at 1 year. The use of UDCA as adjuvant therapy for patients undergoing liver transplantation who are treated with a cyclosporine-based immunosuppressive regimen should be considered.
Barnes
D
D
Department of Gastroenterology, Cleveland Clinic Foundation, OH 44195, USA.
Talenti
D
D
Cammell
G
G
Goormastic
M
M
Farquhar
L
L
Henderson
M
M
Vogt
D
D
Mayes
J
J
Westveer
M K
MK
Carey
W
W
D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D014580:Ursodeoxycholic Acid