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Ursodeoxycholic Acid in Liver Cirrhosis: An Evidence-Based Review

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Pharmacotherapy for Liver Cirrhosis and Its Complications

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Abstract

Ursodeoxycholic acid (UDCA) is a drug with multiple hepatoprotectant and anticholestatic properties. It is used extensively for the dissolution of gallstones and for the treatment of various cholestatic liver diseases. UDCA modifies the constituents of the bile acid pool, stimulates hepatobiliary secretion, exerts cytoprotective effects, inhibits bile acid absorption by cholangiocytes, and exerts immunomodulatory action. These cytoprotective effects alleviate hepatic inflammation and provide potential anti-fibrotic property of this compound. The mechanism involved in the direct inhibitory fibrogenetic effects is unclear, and the data concerning it is extremely limited. In clinical studies, UDCA has been shown to delay the progression of fibrosis, stabilize portal pressure, and delay development of varices and clinical decompensation in patients with primary biliary cholangitis. The effects of UDCA on liver fibrosis and cirrhosis in other chronic cholestatic disorders show heterogeneous results. In non-cholestatic disorders, UDCA demonstrated limited clinical benefits, and currently, there is insufficient evidence to support its use in these conditions. It should be emphasized that there is a possibility that the treatment duration in the studies may not be of sufficient length for the drug to show the effects, as the fibrosis may progress slowly. Future studies are required to elucidate long-term clinical benefits in conditions, such as cirrhosis, and also to investigate any potential cirrhosis-related complications.

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References

  1. Beuers U. Drug insight: mechanisms and sites of action of ursodeoxycholic acid in cholestasis. Nat Clin Pract Gastroenterol Hepatol. 2006;3:318–28.

    Google Scholar 

  2. Paumgartner G, Beuers U. Mechanisms of action and therapeutic efficacy of ursodeoxycholic acid in cholestatic liver disease. Clin Liver Dis. 2004;8:67–81, vi.

    Google Scholar 

  3. Angulo P. Use of ursodeoxycholic acid in patients with liver disease. Curr Gastroenterol Rep. 2002;4:37–44.

    Google Scholar 

  4. Perez MJ, Briz O. Bile-acid-induced cell injury and protection. World J Gastroenterol. 2009;15:1677–89.

    Google Scholar 

  5. Tang N, Zhang Y, Liang Q, Liu Z, Shi Y. The role of ursodeoxycholic acid on cholestatic hepatic fibrosis in infant rats. Mol Med Rep. 2018;17:3837–44.

    Google Scholar 

  6. Ye HL, Zhang JW, Chen XZ, Wu PB, Chen L, Zhang G. Ursodeoxycholic acid alleviates experimental liver fibrosis involving inhibition of autophagy. Life Sci. 2020;242:117175.

    Google Scholar 

  7. Zhang LX, Liang TJ, Tan YR, Ren WH, Han GQ, Zhang J, et al. Protective effects of ursodeoxycholic acid against immune-mediated liver fibrosis in rats. Hepato-Gastroenterology. 2010;57:1196–202.

    Google Scholar 

  8. Schiedermaier P, Hansen S, Asdonk D, Brensing K, Sauerbruch T. Effects of ursodeoxycholic acid on splanchnic and systemic hemodynamics. A double-blind, cross-over, placebo-controlled study in healthy volunteers. Digestion. 2000;61:107–12.

    Google Scholar 

  9. Berzigotti A, Bellot P, De Gottardi A, Garcia-Pagan JC, Gagnon C, Spenard J, et al. NCX-1000, a nitric oxide-releasing derivative of UDCA, does not decrease portal pressure in patients with cirrhosis: results of a randomized, double-blind, dose-escalating study. Am J Gastroenterol. 2010;105:1094–101.

    Google Scholar 

  10. Angulo P, Dickson ER, Therneau TM, Jorgensen RA, Smith C, DeSotel CK, et al. Comparison of three doses of ursodeoxycholic acid in the treatment of primary biliary cirrhosis: a randomized trial. J Hepatol. 1999;30:830–5.

    Google Scholar 

  11. Corpechot C, Carrat F, Bonnand AM, Poupon RE, Poupon R. The effect of ursodeoxycholic acid therapy on liver fibrosis progression in primary biliary cirrhosis. Hepatology. 2000;32:1196–9.

    Google Scholar 

  12. Mayo MJ. Portal hypertension in primary biliary cirrhosis: a potentially reversible harbinger of demise. Gastroenterology. 2008;135:1450–1.

    Google Scholar 

  13. Huet PM, Vincent C, Deslaurier J, Cote J, Matsutami S, Boileau R, et al. Portal hypertension and primary biliary cirrhosis: effect of long-term ursodeoxycholic acid treatment. Gastroenterology. 2008;135:1552–60.

    Google Scholar 

  14. Lindor KD, Jorgensen RA, Therneau TM, Malinchoc M, Dickson ER. Ursodeoxycholic acid delays the onset of esophageal varices in primary biliary cirrhosis. Mayo Clin Proc. 1997;72:1137–40.

    Google Scholar 

  15. Harms MH, de Veer RC, Lammers WJ, Corpechot C, Thorburn D, Janssen HLA, et al. Number needed to treat with ursodeoxycholic acid therapy to prevent liver transplantation or death in primary biliary cholangitis. Gut. 2020;69:1502–9.

    Google Scholar 

  16. Pinyopornpanish K, Chadalavada P, Talal Sarmini M, Khoudari G, Alomari M, Padbidri V, et al. Simplified 6-month prediction scores for primary biliary cholangitis patients treated with ursodeoxycholic acid. Eur J Gastroenterol Hepatol. 2022;34:411–6.

    Google Scholar 

  17. Chen S, Duan W, You H, Jia J. A brief review on prognostic models of primary biliary cholangitis. Hepatol Int. 2017;11:412–8.

    Google Scholar 

  18. Kumagi T, Guindi M, Fischer SE, Arenovich T, Abdalian R, Coltescu C, et al. Baseline ductopenia and treatment response predict long-term histological progression in primary biliary cirrhosis. Am J Gastroenterol. 2010;105:2186–94.

    Google Scholar 

  19. Ornolfsson KT, Lund SH, Olafsson S, Bergmann OM, Bjornsson ES. Biochemical response to ursodeoxycholic acid among PBC patients: a nationwide population-based study. Scand J Gastroenterol. 2019;54:609–16.

    Google Scholar 

  20. John BV, Khakoo NS, Schwartz KB, Aitchenson G, Levy C, Dahman B, et al. Ursodeoxycholic acid response is associated with reduced mortality in primary biliary cholangitis with compensated cirrhosis. Am J Gastroenterol. 2021;116:1913–23.

    Google Scholar 

  21. Lindor KD. Ursodiol for primary sclerosing cholangitis. Mayo primary Sclerosing cholangitis-Ursodeoxycholic acid study group. N Engl J Med. 1997;336:691–5.

    Google Scholar 

  22. Olsson R, Boberg KM, de Muckadell OS, Lindgren S, Hultcrantz R, Folvik G, et al. High-dose ursodeoxycholic acid in primary sclerosing cholangitis: a 5-year multicenter, randomized, controlled study. Gastroenterology. 2005;129:1464–72.

    Google Scholar 

  23. Lindor KD, Kowdley KV, Luketic VA, Harrison ME, McCashland T, Befeler AS, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology. 2009;50:808–14.

    Google Scholar 

  24. Lindblad A, Glaumann H, Strandvik B. A two-year prospective study of the effect of ursodeoxycholic acid on urinary bile acid excretion and liver morphology in cystic fibrosis-associated liver disease. Hepatology. 1998;27:166–74.

    Google Scholar 

  25. van der Feen C, van der Doef HP, van der Ent CK, Houwen RH. Ursodeoxycholic acid treatment is associated with improvement of liver stiffness in cystic fibrosis patients. J Cyst Fibros. 2016;15:834–8.

    Google Scholar 

  26. Toledano MB, Mukherjee SK, Howell J, Westaby D, Khan SA, Bilton D, et al. The emerging burden of liver disease in cystic fibrosis patients: a UK nationwide study. PLoS One. 2019;14:e0212779.

    Google Scholar 

  27. Boelle PY, Debray D, Guillot L, Clement A, Corvol H, French CFMGSI. Cystic fibrosis liver disease: outcomes and risk factors in a large cohort of French patients. Hepatology. 2019;69:1648–56.

    Google Scholar 

  28. Colombo C, Alicandro G, Oliver M, Lewindon PJ, Ramm GA, Ooi CY, et al. Ursodeoxycholic acid and liver disease associated with cystic fibrosis: a multicenter cohort study. J Cyst Fibros. 2022;21:220–6.

    Google Scholar 

  29. Jacquemin E, Hermans D, Myara A, Habes D, Debray D, Hadchouel M, et al. Ursodeoxycholic acid therapy in pediatric patients with progressive familial intrahepatic cholestasis. Hepatology. 1997;25:519–23.

    Google Scholar 

  30. Frider B, Castillo A, Gordo-Gilart R, Bruno A, Amante M, Alvarez L, et al. Reversal of advanced fibrosis after long-term ursodeoxycholic acid therapy in a patient with residual expression of MDR3. Ann Hepatol. 2015;14:745–51.

    Google Scholar 

  31. Pathil A, Mueller J, Warth A, Chamulitrat W, Stremmel W. Ursodeoxycholyl lysophosphatidylethanolamide improves steatosis and inflammation in murine models of nonalcoholic fatty liver disease. Hepatology. 2012;55:1369–78.

    Google Scholar 

  32. Lindor KD, Kowdley KV, Heathcote EJ, Harrison ME, Jorgensen R, Angulo P, et al. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology. 2004;39:770–8.

    Google Scholar 

  33. Leuschner UF, Lindenthal B, Herrmann G, Arnold JC, Rossle M, Cordes HJ, et al. High-dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a double-blind, randomized, placebo-controlled trial. Hepatology. 2010;52:472–9.

    Google Scholar 

  34. Ratziu V, de Ledinghen V, Oberti F, Mathurin P, Wartelle-Bladou C, Renou C, et al. A randomized controlled trial of high-dose ursodesoxycholic acid for nonalcoholic steatohepatitis. J Hepatol. 2011;54:1011–9.

    Google Scholar 

  35. Nakamura K, Yoneda M, Yokohama S, Tamori K, Sato Y, Aso K, et al. Efficacy of ursodeoxycholic acid in Japanese patients with type 1 autoimmune hepatitis. J Gastroenterol Hepatol. 1998;13:490–5.

    Google Scholar 

  36. Czaja AJ, Carpenter HA, Lindor KD. Ursodeoxycholic acid as adjunctive therapy for problematic type 1 autoimmune hepatitis: a randomized placebo-controlled treatment trial. Hepatology. 1999;30:1381–6.

    Google Scholar 

  37. Pelletier G, Roulot D, Davion T, Masliah C, Causse X, Oberti F, et al. A randomized controlled trial of ursodeoxycholic acid in patients with alcohol-induced cirrhosis and jaundice. Hepatology. 2003;37:887–92.

    Google Scholar 

  38. Fabbri C, Marchetto S, Pezzoli A, Accogli E, Fusaroli P, Azzaroli F, et al. Efficacy of ursodeoxycholic acid in association with alpha-interferon for chronic hepatitis C in alpha-interferon non-responder patients. Eur J Gastroenterol Hepatol. 2000;12:511–5.

    Google Scholar 

  39. Lirussi F, Beccarello A, Bortolato L, Morselli-Labate AM, Crovatto M, Ceselli S, et al. Long-term treatment of chronic hepatitis C with ursodeoxycholic acid: influence of HCV genotypes and severity of liver disease. Liver. 1999;19:381–8.

    Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

    Kanokwan Pinyopornpanish

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  1. Kanokwan Pinyopornpanish
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Editors and Affiliations

  1. Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China

    Xingshun Qi

  2. Faculty of Liver Disease of Chinese People’s Liberation Army General Hospital, The Fifth Medical Center of the Chinese People’s Liberation Army General Hospital, Beijing, China

    Yongping Yang

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Pinyopornpanish, K. (2022). Ursodeoxycholic Acid in Liver Cirrhosis: An Evidence-Based Review. In: Qi, X., Yang, Y. (eds) Pharmacotherapy for Liver Cirrhosis and Its Complications. Springer, Singapore. https://doi.org/10.1007/978-981-19-2615-0_5

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  • DOI: https://doi.org/10.1007/978-981-19-2615-0_5

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  • Online ISBN: 978-981-19-2615-0

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