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. 2011 Nov;34(10):1185-92.
doi: 10.1111/j.1365-2036.2011.04863.x. Epub 2011 Sep 29.

High-dose ursodeoxycholic acid increases risk of adverse outcomes in patients with early stage primary sclerosing cholangitis

M H Imam  1 , E Sinakos, A A Gossard, K V Kowdley, V A C Luketic, M Edwyn Harrison, T McCashland, A S Befeler, D Harnois, R Jorgensen, J Petz, J Keach, A C DeCook, F Enders, K D Lindor
Affiliations

High-dose ursodeoxycholic acid increases risk of adverse outcomes in patients with early stage primary sclerosing cholangitis

M H Imam et al. Aliment Pharmacol Ther. 2011 Nov.

Abstract

Background: Ursodeoxycholic acid (UDCA) in a dose of 28-30 mg/kg/day increases the likelihood of clinical deterioration of primary sclerosing cholangitis (PSC) patients.

Aim: To compare the risk of adverse clinical endpoints in patients with varying disease status.

Methods: We reviewed records from patients previously enrolled in a study evaluating the effects of high dose (28-30 mg/kg/day) UDCA in PSC. Patients were grouped according to treatment (UDCA vs. placebo) and baseline disease status (histological stage of PSC, total serum bilirubin). Development of clinical endpoints including death, liver transplantation, cirrhosis, oesophageal varices and cholangiocarcinoma was sought.

Results: A total of 150 patients were included of whom 49 patients developed endpoints. There was an increased development of endpoints among patients using UDCA vs. placebo (14 vs. 4, P=0.0151) with early histological disease (stage 1-2, n=88) but not with late stage (stage 3-4, n=62) disease (17 vs. 14, P=0.2031). Occurrence of clinical endpoints was also higher in patients receiving UDCA vs. placebo (16 vs. 2, P=0.0008) with normal bilirubin levels (total bilirubin ≤1.0 mg/dL) but not in patients with elevated bilirubin levels (15 vs. 16, P=0.6018). Among patients not reaching endpoints 31.7% had normalisation of their alkaline phosphatase levels when compared to 14.3% in patients who reached endpoints (P=0.073).

Conclusion: The increased risk of adverse events with UDCA treatment when compared with placebo is only apparent in patients with early histological stage disease or normal total bilirubin.

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Figures

Figure 1
Figure 1
Number of endpoints* in primary sclerosing cholangitis patients according to stage of disease * Endpoints include death, transplantation, meeting minimal listing criteria, development of varices, cholangiocarcinoma or progression to cirrhosis
Figure 2
Figure 2
Number of endpoints* in primary sclerosing cholangitis patients according to total serum bilirubin level * Endpoints include death, transplantation, meeting minimal listing criteria, development of varices, cholangiocarcinoma or progression to cirrhosis
Figure 3
Figure 3
Kaplan Meyer curve representing the time to development of endpoints in patients with early and late stage disease receiving UDCA.
See this image and copyright information in PMC

Comment in

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