High dose ursodeoxycholic acid in primary sclerosing cholangitis does not prevent colorectal neoplasia.
BACKGROUND
Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) have a high risk of developing colorectal cancer and dysplasia. Ursodeoxycholic acid (UDCA) has been suggested to have chemopreventive effects on the development of colorectal cancer and dysplasia but long-term data and larger trials are lacking.


OBJECTIVE
To evaluate the effect of high dose (17-23 mg/kg/day) UDCA on colorectal neoplasia in a cohort of patients with PSC and IBD.


METHODS
From our previous 5-year randomised controlled trial of UDCA vs. placebo in PSC, we performed a follow-up of 98 patients with concomitant IBD from entry of the trial 1996-1997 until 2009 for development of colorectal cancer or dysplasia.


RESULTS
The total follow-up time was 760 person-years. Dysplasia/cancer-free survival was compared between placebo- (n = 50) and UDCA-treated (n = 48) patients. There was a similar frequency of dysplasia or cancer after 5 years between patients originally assigned to UDCA or placebo (13% vs. 16%) and no difference in dysplasia/cancer-free survival (P = 0.46, log rank test). At the end of 2009 no difference in cancer-free survival was detected, 30% of the placebo patients compared with 27% of UDCA patients had developed colorectal cancer or dysplasia.


CONCLUSIONS
Long-term high dose ursodeoxycholic acid does not prevent colorectal cancer or dysplasia in patients with primary sclerosing cholangitis-associated inflammatory bowel disease.
Department of Gastroenterology and Hepatology, Karolinska University Hospital, Huddinge, Stockholm, Sweden. lina.lindstrom@karolinska.se
L
L
Lindström
K M
KM
Boberg
O
O
Wikman
I
I
Friis-Liby
R
R
Hultcrantz
H
H
Prytz
H
H
Sandberg-Gertzén
P
P
Sangfelt
A
A
Rydning
G
G
Folvik
M
M
Gangsøy-Kristiansen
A
A
Danielsson
Annika
A
Bergquist
D000293:Adolescent; D000328:Adult; D000368:Aged; D002756:Cholagogues and Choleretics / Q000008:administration & dosage*; D015209:Cholangitis, Sclerosing / Q000150:complications / Q000188:drug therapy*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000209:etiology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D013548:Sweden; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage*; D055815:Young Adult
D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid