High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis #

Abstract

Previous controlled trials are inconclusive regarding the efficacy of ursodeoxycholic acid (UDCA) for treating primary sclerosing cholangitis (PSC). One hundred fifty adult patients with PSC were enrolled in a long-term, randomized, double-blind controlled trial of highdose UDCA (28-30 mg/kg/day) versus placebo. Liver biopsy and cholangiography were performed before randomization and after 5 years. The primary outcome measures were development of cirrhosis, varices, cholangiocarcinoma, liver transplantation, or death. The study was terminated after 6 years due to futility. At enrollment, the UDCA (n ‫؍‬ 76) and placebo (n ‫؍‬ 74) groups were similar with respect to sex, age, duration of disease, serum aspartate aminotransferase and alkaline phosphatase levels, liver histology, and Mayo risk score. During therapy, aspartate aminotransferase and alkaline phosphatase levels decreased more in the UDCA group than the placebo group (P < 0.01), but improvements in liver tests were not associated with decreased endpoints. By the end of the study, 30 patients in the UDCA group (39%) versus 19 patients in the placebo group (26%) had reached one of the pre-established clinical endpoints. After adjustment for baseline stratification characteristics, the risk of a primary endpoint was 2.3 times greater for patients on UDCA than for those on placebo (P < 0.01) and 2.1 times greater for death, transplantation, or minimal listing criteria (P ‫؍‬ 0.038). Serious adverse events were more common in the UDCA group than the placebo group (63% versus 37% [P < 0.01]). Conclusion: Long-term, high-dose UDCA therapy is associated with improvement in serum liver tests in PSC but does not improve survival and was associated with higher rates of serious adverse events. (HEPATOLOGY 2009;50:808-814.)

ARFI elastography in patients with chronic autoimmune liver diseases: A preliminary study

“…AIH was diagnosed on the basis of the simplified criteria described by the International AIH Group [27]. The diagnosis of PSC was based on the criteria of Lindor et al [28], and the criteria of Boberg et al were used to diagnose overlap syndromes [29]. Exclusion criteria were: a) multifactorial liver disease (other than an overlap syndrome); b) ascitic decompensation; c) previous liver transplantation (OLT); d) pregnancy; e) liver tumors; f) alcohol abuse (>20 g/day); g) absence of consent to participation in the study.…”

Evidence-based clinical practice guidelines for liver cirrhosis 2015

“…An RCT revealed that high-dose UDCA therapy (28-30 mg/kg/day) did not improve survival, although it suppressed serum ALT and alkaline phosphatase levels [100]. The therapy was associated with increased risk of esophagogastric varices and mortality, suggesting a risk of high-dose UDCA therapy for patients with primary sclerosing cholangitis [100].…”

“…The therapy was associated with increased risk of esophagogastric varices and mortality, suggesting a risk of high-dose UDCA therapy for patients with primary sclerosing cholangitis [100]. On the basis of variable data on its effects on liver tests and survival [100][101][102][103], UDCA therapy is not recommended in the American Association for the Study of Liver Diseases (AASLD) [104] and European Association for the Study of the Liver (EASL) [105] guidelines. We propose its careful use as a treatment option after assessment of the benefit-risk balance.…”

A review of liver disorders in inflammatory bowel disease (IBD)

“…Higher doses of UCDA (20-30 mg/kg/day) have been shown to be detrimental, rather than to have any substantial clinical benefit [72][73][74][75][76]. UCDA does not improve liver histology or liver transplant free survival, nor does it prevent the development of cholangiocarcinoma, colonic adenomas, colon cancer or incidence of death [73,[77][78][79].…”

“…Higher doses of UCDA (20-30 mg/kg/day) have been shown to be detrimental, rather than to have any substantial clinical benefit [72][73][74][75][76]. UCDA does not improve liver histology or liver transplant free survival, nor does it prevent the development of cholangiocarcinoma, colonic adenomas, colon cancer or incidence of death [73,[77][78][79]. Corticosteroids have not been proven effective either as single agents or when used with colchicine or ursodeoxycholic acid [80], nor have methotrexate, colchicine, pentoxifylline, etanercept, or mycophenolate mofetil proved useful in PSC [81][82][83][84][85][86].…”