High-dose ursodeoxycholic acid in primary sclerosing cholangitis: a 5-year multicenter, randomized, controlled study.
OBJECTIVE
There is no medical treatment of proven benefit for primary sclerosing cholangitis. This study aimed at studying the effect of a higher dose of ursodeoxycholic acid than previously used on survival, symptoms, biochemistry, and quality of life in this disease.


METHODS
A randomized placebo-controlled study was performed in tertiary and secondary gastroenterology units. A total of 219 patients were randomized to 17 to 23 mg/kg body weight per day of ursodeoxycholic acid (n = 110) or placebo (n = 109) for 5 years. Follow-up data are available from 97 patients randomized to ursodeoxycholic acid and for 101 randomized to placebo. Quality of life was assessed by using the Medical Outcomes Study 36-item Short-Form Health Survey.


RESULTS
The combined end point "death or liver transplantation" occurred in 7 of 97 (7.2%) patients in the ursodeoxycholic acid group vs 11 of 101 (10.9%) patients in the placebo group (P = .368; 95% confidence interval, -12.2% to 4.7%). The occurrence of liver transplantation as a single end point showed a similar positive trend for ursodeoxycholic acid treatment (5/97 [5.2%] vs 8/101 [7.9%]; 95% confidence interval, -10.4% to 4.6%). Three ursodeoxycholic acid and 4 placebo patients died from cholangiocarcinoma, and 1 placebo patient died from liver failure. Alkaline phosphatase and alanine aminotransferase tended to decrease during the first 6 months. There were no differences between the 2 groups in symptoms or quality of life. Analyses of serum ursodeoxycholic acid concentration gave no evidence that noncompliance may have influenced the results.


CONCLUSIONS
This study found no statistically significant beneficial effect of a higher dose of ursodeoxycholic acid than previously used on survival or prevention of cholangiocarcinoma in primary sclerosing cholangitis.
Olsson
Rolf
R
Department of Medicine, Sahlgrenska University Hospital/Sahlgrenska, Gotheburg, Sweden. rolf.olsson@medicine.gu.se
Boberg
Kirsten M
KM
de Muckadell
Ove Schaffalitsky
OS
Lindgren
Stefan
S
Hultcrantz
Rolf
R
Folvik
Geir
G
Bell
Helge
H
Gangsøy-Kristiansen
Magnhild
M
Matre
Jon
J
Rydning
Andreas
A
Wikman
Ola
O
Danielsson
Ake
A
Sandberg-Gertzén
Hanna
H
Ung
Kjell-Arne
KA
Eriksson
Anders
A
Lööf
Lars
L
Prytz
Hanne
H
Marschall
Hanns-Ulrich
HU
Broomé
Ulrika
U
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D001647:Bile Acids and Salts / Q000097:blood; D002756:Cholagogues and Choleretics / Q000008:administration & dosage* / Q000009:adverse effects; D015209:Cholangitis, Sclerosing / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017093:Liver Failure / Q000401:mortality / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D011788:Quality of Life; D016019:Survival Analysis; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage* / Q000009:adverse effects
D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase