Ursodeoxycholic acid treatment of refractory chronic graft-versus-host disease of the liver.
OBJECTIVE
To determine the safety and efficacy of ursodeoxycholic acid treatment in patients with chronic graft-versus-host disease (GVHD) of the liver.


METHODS
Open-label study in which each patient served as his or her own control.


METHODS
Private practice and a university bone marrow transplant center.


METHODS
Twelve patients with refractory chronic GVHD of the liver were studied after allogeneic bone marrow transplantation.


METHODS
After baseline data collection, patients were given ursodeoxycholic acid (UDCA, 10 to 15 mg/kg body weight per day) for 6 weeks. After discontinuation of the drug, patients were followed for an additional 6 weeks. Doses of immunosuppressive drugs were unchanged for these 12 weeks.


METHODS
Signs, symptoms, Karnofsky performance scores, hematocrit, total leukocyte count, absolute neutrophil count, platelet count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, gamma-glutamyltransferase (GGT), total serum bilirubin, prothrombin time, serum creatinine, and blood urea nitrogen were assessed.


RESULTS
Serum tests of cholestatic liver injury measured at 2, 4, and 6 weeks showed improvement compared with baseline. At 6 weeks, the percent decrease from baseline in total serum bilirubin was 33% (P less than 0.005); in alkaline phosphatase the decrease was 32% (P less than 0.038); and in AST the decrease was 37% (P less than 0.007). After discontinuation of UDCA therapy, 11 patients were followed for 6 additional weeks. All showed significant worsening in liver function test results. Symptom scores were unchanged throughout the study. One patient with pruritus improved while receiving therapy with UDCA. No adverse effects were observed.


CONCLUSIONS
Therapy with UDCA was safe, well-tolerated, and efficacious in the short-term treatment of refractory chronic GVHD of the liver. Further investigation is needed to evaluate the long-term effects of UDCA therapy.
Fried
R H
RH
Fred Hutchinson Cancer Research Center, Seattle, Washington.
Murakami
C S
CS
Fisher
L D
LD
Willson
R A
RA
Sullivan
K M
KM
McDonald
G B
GB
D001663:Bilirubin / Q000097:blood; D002779:Cholestasis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D002908:Chronic Disease; D006086:Graft vs Host Disease / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D008107:Liver Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
D014580:Ursodeoxycholic Acid; D001663:Bilirubin