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Use of Ursodeoxycholic Acid Therapy in the Treatment of Cholestatic Liver Diseases
large, multicenter, placebo-controlled trial of high-dose UDCA therapy in
Table 1: Summary of Evidence Supporting the Use of
PSC is currently under way in the US.
Ursodeoxycholic Acid Therapy in Cholestatic Liver Disease
Scenario 3
Disease Dosage of UDCA Strength of Evidence Reference
A 55-year-old female with an increased body mass index (BMI) of 32
PBC 13–15mg/kg/day Evidence of improvement 16, 17
in a randomized, placebo-
presents to you with concerns regarding liver tests noted to be three times
controlled trial
higher than normal. Her evaluation, including viral and autoimmune
PSC 20–30mg/kg/day Promising pilot study and 18, 19
serologies, is negative. A liver biopsy confirms moderate steatosis, a lobular,
a randomized, placebo-
grade 2 hepatitis, and stage 2 fibrosis. She has non-alcoholic steatohepatitis
controlled trial currently
(NASH). You question the value of UDCA therapy.
under way
NASH 12–15mg/kg/day Lack of evidence in a large 21, 22,
In an initial pilot study of UDCA in 24 patients with NASH, a significant placebo-controlled trial 23, 24
improvement in liver tests was reported.
20
Recently, however, a randomized,
NASH 12–15mg/kg/day Evidence of improvement in 25
placebo-controlled trial failed to show improvement using UDCA treatment
plus vitamin E a small, randomized,
at a dose of 13–15mg/kg/day over placebo in 166 patients followed for two
400IU daily placebo-controlled trial
years with biopsy-documented NASH.
21
These results were also
Drug- or TPN- 13–15mg/kg/day Case reports only 2, 6, 26
induced cholestasis
demonstrated in several other smaller trials.
22–24
A European trial of 48
patients with elevated liver tests and biopsy-proven NASH was recently
UDCA = ursodehoxycholic acid; PBC = primary biliary cirrhosis; PSC = primary sclerosing cholangitis;
NASH = non-alcoholic steatohepatitis; TPN = total parenteral nutrition.
reported in Clinical Gastroenterology and Hepatology (2006).
25
Patients
were randomized to receive UDCA 12–15mg/kg/day and vitamin E 400IU Part of the reason for the prevalent use of UDCA therapy in the treatment of
daily, UDCA plus placebo, or placebo plus placebo for two years. cholestatic liver diseases is the low risk profile of the drug. All formulations of
Improvement was reported in both liver tests and fibrosis score on biopsy the drug have been shown to have minimal side effects. My personal
in the UDCA plus vitamin E group over both the UDCA plus placebo group experience is that the Canadian Ursofalk tablets are better tolerated with fewer
and the double-placebo group. There were no significant changes in BMI of the gastrointestinal side effects commonly seen in patients treated with
in either of the groups. Additional treatment trials will be helpful in higher-dose therapy. A study has also demonstrated improved bioavailability in
establishing recommendations regarding the use of UDCA therapy in the the tablet form of the drug (e.g. the Canadian Ursofalk tablets at a dose of
treatment of NASH. 250, 500, or 750mg) compared with the UDCA capsule preparations.
27
Other Treatment Considerations Conclusion
While there have been a number of small case reports demonstrating The clinical efficacy of UDCA therapy in the treatment of PBC at a dose of
improvement in both cholestasis and symptoms in patients with drug-induced 13–15mg/kg/day has been clearly demonstrated. There is also some
liver disease,
26
total parenteral nutrition (TPN)-induced cholestasis, and encouraging evidence supporting its use in the treatment of PSC (in higher
allograft dysfunction following liver transplant, there have been no placebo- doses), NASH (in combination with vitamin E), and drug- or TPN-induced
controlled trials to study the drug’s effect in these indications.
2,6,26
That being cholestasis. Further studies are needed to better define the use of UDCA
said, it is common practice to use UDCA therapy in many of these instances. therapy in the treatment of a number of cholestatic liver diseases. ■
1. Iwasaki T, Uber die konstitution der urso-deoxycholsaure, Z Physiol acids on interferon-induced 2’,5’-adenylate synthesis and NK cell ursodeoxycholic acid as a therapy for patietns with primary
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Curr Gastroenterol Rep, 2002;4:37–44. class II major histocompatibility complex molecules in primary biliary clofibrate in the treatment of non-alcohol-induced steatohepatitis: a
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5. Trauner M, Graziadei IW, Mechanism of action and therapeutic production in primary biliary cirrhosis, Dig Dis Sci, 1996;41:1487–93. 23. Mendez-Sanchez N, Gonzalez V, Chavez-Tapia N, et al., Weight
applications of ursodeoxycholic acid in chronic liver diseases, Aliment 14. Yamazaki K, Suzuki K, Nakamura A, et al., Ursodeoxycholic acid reduction and ursodeoxycholic acid in subjects with nonalcoholic
Pharmacol Ther, 1999;13:979–95. inhibits eosinophil degranulation in patients with primary biliary fatty liver disease. A double-blind placebo-controlled trial, Ann
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