Genomes and Genes
cholagogues and choleretics
Summary: Gastrointestinal agents that stimulate the flow of bile into the duodenum (cholagogues) or stimulate the production of bile by the liver (choleretic).
- Lee J, Belanger A, Doucette J, Stanca C, Friedman S, Bach N. Transplantation trends in primary biliary cirrhosis. Clin Gastroenterol Hepatol. 2007;5:1313-5 pubmed..434; P = .083). The liver transplantation burden of PBC in the United States decreased between 1995 and 2006. This is despite an increase in total liver transplants and no change in transplant rates for PSC. ..
- Sokolovic D, Nikolic J, Kocic G, Jevtovic Stoimenov T, Veljkovic A, Stojanovic M, et al. The effect of ursodeoxycholic acid on oxidative stress level and DNase activity in rat liver after bile duct ligation. Drug Chem Toxicol. 2013;36:141-8 pubmed publisher..Therefore, UDCA may be useful in the preservation of liver function in cholestasis treatment. ..
- Lindor K, Kowdley K, Luketic V, Harrison M, McCashland T, Befeler A, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology. 2009;50:808-14 pubmed publisher..01]). 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. ..
- Kaya O, Ozdemir F, Atli M, Aslan V, Cağatay M, Anlar M, et al. The effects of ciprofloxacin and ursodeoxycholic acid on bacterial translocation in obstructive jaundice. Turk J Gastroenterol. 2009;20:186-91 pubmed..Ciprofloxacin and ursodeoxycholic acid have a synergic effect on prevention of bacterial translocation in obstructive jaundice. ..
- Arenas F, Hervias I, Uriz M, Joplin R, Prieto J, Medina J. Combination of ursodeoxycholic acid and glucocorticoids upregulates the AE2 alternate promoter in human liver cells. J Clin Invest. 2008;118:695-709 pubmed publisher..Our data provide a potential molecular explanation for the beneficial effects of the combination of UDCA and glucocorticoids in PBC patients with inadequate response to UDCA monotherapy...
- Amaral J, Castro R, Sola S, Steer C, Rodrigues C. p53 is a key molecular target of ursodeoxycholic acid in regulating apoptosis. J Biol Chem. 2007;282:34250-9 pubmed..In conclusion, these results further clarify the antiapoptotic mechanism of UDCA and suggest that modulation of Mdm-2/p53 interaction is a prime target for this bile acid. ..
- Eaton J, Silveira M, Pardi D, Sinakos E, Kowdley K, Luketic V, et al. High-dose ursodeoxycholic acid is associated with the development of colorectal neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis. Am J Gastroenterol. 2011;106:1638-45 pubmed publisher..44, 95% confidence interval: 1.30-20.10, P=0.02). Long-term use of high-dose UDCA is associated with an increased risk of colorectal neoplasia in patients with UC and PSC. ..
- Berkhout M, Roelofs H, Friederich P, van Schaik A, Gosens M, Marian B, et al. Ursodeoxycholic acid intervention in patients with familial adenomatous polyposis: a pilot study. Transl Res. 2007;150:147-9 pubmed
- Saleh M, Abdo K. Intrahepatic cholestasis of pregnancy: review of the literature and evaluation of current evidence. J Womens Health (Larchmt). 2007;16:833-41 pubmed..To provide an overview of the epidemiology, etiology, pathogenesis, diagnosis, and management of intrahepatic cholestasis of pregnancy...
- Wang S, Tang H, Chen G, Xu J, Zhong L, Wang Z, et al. Effect of ursodeoxycholic acid administration after liver transplantation on serum liver tests and biliary complications: a randomized clinical trial. Digestion. 2012;86:208-17 pubmed publisher..UDCA administration early after DCD-OLT improves serum liver tests and decreases the incidence of biliary sludge and casts within the 1st postoperative year but does not affect overall outcome up to 5 years after OLT. ..
- Hazzan R, Tur Kaspa R. Bezafibrate treatment of primary biliary cirrhosis following incomplete response to ursodeoxycholic acid. J Clin Gastroenterol. 2010;44:371-3 pubmed publisher..Combination therapy with bezafibrate and UDCA improves the biochemical profile of patients with PBC who respond only partially to UDCA. A larger controlled study is needed to evaluate the clinical implications of these findings. ..
- Mayo M. Natural history of primary biliary cirrhosis. Clin Liver Dis. 2008;12:277-88; viii pubmed publisher..A need remains to better define and predict the course of symptomatic and asymptomatic patients on and off UDCA in order to better evaluate outcomes of clinical trials. ..
- Corpechot C, Abenavoli L, Rabahi N, Chretien Y, Andreani T, Johanet C, et al. Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis. Hepatology. 2008;48:871-7 pubmed publisher..3). Antinuclear antibodies against gp210 or Sp100 proteins were associated with death or LT in univariate but not in multivariate analysis...
- Miloh T, Arnon R, Shneider B, Suchy F, Kerkar N. A retrospective single-center review of primary sclerosing cholangitis in children. Clin Gastroenterol Hepatol. 2009;7:239-45 pubmed publisher..Levels of serum liver enzymes normalized after therapy with UDCA, including patients with positive autoimmune markers without histologic features of autoimmune hepatitis. ..
- 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 pubmed publisher..There were no safety issues in this population. Treatment with HD-UDCA was safe, improved aminotransferase levels, serum fibrosis markers, and selected metabolic parameters. Studies with histologic end points are warranted. ..
- Wree A, Dechene A, Herzer K, Hilgard P, Syn W, Gerken G, et al. Steroid and ursodesoxycholic Acid combination therapy in severe drug-induced liver injury. Digestion. 2011;84:54-9 pubmed publisher..Treatment of severe DILI with corticosteroids (both pulse and step-down therapy) and UDCA appears to be safe, and leads to a more rapid reduction in bilirubin and transaminases after DILI. ..
- Roma M, Toledo F, Boaglio A, Basiglio C, Crocenzi F, Sanchez Pozzi E. Ursodeoxycholic acid in cholestasis: linking action mechanisms to therapeutic applications. Clin Sci (Lond). 2011;121:523-44 pubmed publisher..We predict a long-lasting use of UDCA as the therapeutic agent of choice in cholestasis. ..
- Parc Y, Desaint B, Flejou J, Lefevre J, Serfaty L, Vienne A, et al. The effect of ursodesoxycholic acid on duodenal adenomas in familial adenomatous polyposis: a prospective randomized placebo-control trial. Colorectal Dis. 2012;14:854-60 pubmed publisher..Studies suggest that biliary acids have a role in the development of duodenal adenomas. The aim of this study was to evaluate the impact of ursodesoxycholic acid (UDCA) on duodenal adenoma formation in patients with FAP...
- Poupon R. Ursodeoxycholic acid and bile-acid mimetics as therapeutic agents for cholestatic liver diseases: an overview of their mechanisms of action. Clin Res Hepatol Gastroenterol. 2012;36 Suppl 1:S3-12 pubmed publisher..In this overview, the biological properties of UDCA, NorUDCA and FXR agonists are highlighted, as well as their overlapping mechanisms of action in inflammatory biliary disorders. ..
- Parry G, Rodrigues C, Aranha M, Hilbert S, Davey C, Kelkar P, et al. Safety, tolerability, and cerebrospinal fluid penetration of ursodeoxycholic Acid in patients with amyotrophic lateral sclerosis. Clin Neuropharmacol. 2010;33:17-21 pubmed publisher..The drug penetrates the cerebrospinal fluid in a dose-dependent manner. A large, placebo-controlled clinical trial is needed to assess the efficacy of ursodeoxycholic acid in treating amyotrophic lateral sclerosis. ..
- Singh S, Khanna S, Pardi D, Loftus E, Talwalkar J. Effect of ursodeoxycholic acid use on the risk of colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease: a systematic review and meta-analysis. Inflamm Bowel Dis. 2013;19:1631-8 pubmed publisher..However, results should be interpreted with caution, given limited reporting of cancer-related outcomes, primarily from tertiary care centers. ..
- Dufour J, Oneta C, Gonvers J, Bihl F, Cerny A, Cereda J, et al. Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin e in nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol. 2006;4:1537-43 pubmed..Two years of treatment with UDCA in combination with vitamin E improved laboratory values and hepatic steatosis of patients with NASH. Larger trials are warranted. ..
- Kanda T, Yokosuka O, Imazeki F, Saisho H. Bezafibrate treatment: a new medical approach for PBC patients?. J Gastroenterol. 2003;38:573-8 pubmed..A new medical approach to primary biliary cirrhosis (PBC) has been desired. We investigated the feasibility of using combination ursodeoxycholic acid (UDCA)-bezafibrate therapy in patients with PBC nonresponsive to UDCA monotherapy...
- Babatin M, Sanai F, Swain M. Methotrexate therapy for the symptomatic treatment of primary biliary cirrhosis patients, who are biochemical incomplete responders to ursodeoxycholic acid therapy. Aliment Pharmacol Ther. 2006;24:813-20 pubmed..Although it has been shown to improve biochemical markers and delay disease progression, its effect upon fatigue and pruritus, is at best uncertain...
- Dahlan Y, Smith L, Simmonds D, Jewell L, Wanless I, Heathcote E, et al. Pediatric-onset primary biliary cirrhosis. Gastroenterology. 2003;125:1476-9 pubmed..In conclusion, we present 2 liver biopsy-confirmed cases of pediatric-onset AMA-positive PBC. With increased awareness of early-onset PBC, further pediatric cases may be discovered. ..
- Kaplan M, Gershwin M. Primary biliary cirrhosis. N Engl J Med. 2005;353:1261-73 pubmed
- Verma A, Maxwell J, Ang L, Davis T, Hodges S, Northfield T, et al. Ursodeoxycholic acid enhances fractional calcium absorption in primary biliary cirrhosis. Osteoporos Int. 2002;13:677-82 pubmed..Long-term studies are required to determine whether this effect can be sustained, and whether a sustained increase in fractional calcium absorption can translate into a favorable change in bone strength in patients with PBC. ..
- Dohmen K, Mizuta T, Nakamuta M, Shimohashi N, Ishibashi H, Yamamoto K. Fenofibrate for patients with asymptomatic primary biliary cirrhosis. World J Gastroenterol. 2004;10:894-8 pubmed
- Bernal Reyes R, Escudero R. [Treatment of non-alcoholic steatohepatitis (NASH). A comparative study of ursodeoxycholic acid and alpha-tocopherol. A preliminary report]. Rev Gastroenterol Mex. 2002;67:70-5 pubmed..The group is small and requires more persons and to be compared with a control group. It is possible that both drugs can be useful in the treatment of NASH; they are well tolerated and allow good fulfillment. ..
- Siegel J, Jorgensen R, Angulo P, Lindor K. Treatment with ursodeoxycholic acid is associated with weight gain in patients with primary biliary cirrhosis. J Clin Gastroenterol. 2003;37:183-5 pubmed..Discussions with PBC patients beginning UDCA treatment should include the beneficial effects this medication has on disease outcome, but should also mention weight gain as a possible side effect. ..
- Hempfling W, Dilger K, Beuers U. Systematic review: ursodeoxycholic acid--adverse effects and drug interactions. Aliment Pharmacol Ther. 2003;18:963-72 pubmed..Ursodeoxycholic acid is generally well tolerated. Drug absorption interactions with anion exchange resins deserve consideration. Metabolic interactions with compounds metabolized by cytochrome P4503A are to be expected. ..
- Pardi D, Loftus E, Kremers W, Keach J, Lindor K. Ursodeoxycholic acid as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis. Gastroenterology. 2003;124:889-93 pubmed..26; 95% confidence interval, 0.07-0.99; P = 0.049). UDCA significantly decreases the risk for developing colorectal dysplasia or cancer in patients with UC and PSC. ..
- Jacoby R, Cole C, Hawk E, Lubet R. Ursodeoxycholate/Sulindac combination treatment effectively prevents intestinal adenomas in a mouse model of polyposis. Gastroenterology. 2004;127:838-44 pubmed..Cyclooxygenase inhibition, when combined with this naturally occurring bile component, may become a promising approach for colon cancer prevention. ..
- Poupon R, Chretien Y, Chazouilleres O, Poupon R, Chwalow J. Quality of life in patients with primary biliary cirrhosis. Hepatology. 2004;40:489-94 pubmed..These effects must be taken into account by clinicians when treating these patients, as they constitute the clinical outcomes that have the most impact on patients' lifestyle and adherence to treatment. ..
- Song S, Byrd J, Koo J, Bresalier R. Bile acids induce MUC2 overexpression in human colon carcinoma cells. Cancer. 2005;103:1606-14 pubmed..Bile acids induced mucin expression in human colon carcinoma cells by increasing MUC2 transcription through a process involving MAP kinase-independent, PKC-dependent activation of AP-1. ..
- Rodrigues C, Spellman S, Sola S, Grande A, Linehan Stieers C, Low W, et al. Neuroprotection by a bile acid in an acute stroke model in the rat. J Cereb Blood Flow Metab. 2002;22:463-71 pubmed..Thus, TUDCA, a clinically safe molecule, may be useful in the treatment of stroke and possibly other apoptosis-associated acute and chronic injuries to the brain. ..
- Germain A, Carvajal J, Glasinovic J, Kato C S, Williamson C. Intrahepatic cholestasis of pregnancy: an intriguing pregnancy-specific disorder. J Soc Gynecol Investig. 2002;9:10-4 pubmed..Intrahepatic cholestasis of pregnancy should be considered a high-risk condition, and careful fetal assessment and appropriate medical intervention might improve perinatal outcome. ..
- Paumgartner G, Beuers U. Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited. Hepatology. 2002;36:525-31 pubmed..Future efforts will focus on definition of additional clinical uses of UDCA, on optimized dosage regimens, as well as on further elucidation of mechanisms of action of UDCA at the molecular level. ..
- Santos V, Lanzoni V, Szejnfeld J, Shigueoka D, Parise E. A randomized double-blind study of the short-time treatment of obese patients with nonalcoholic fatty liver disease with ursodeoxycholic acid. Braz J Med Biol Res. 2003;36:723-9 pubmed..These results show that ursodeoxycholic acid is able to reduce serum levels of hepatic enzymes in patients with nonalcoholic fatty liver disease, but this effect is not related to modifications in liver fat content. ..
- Corpechot C, Carrat F, Poupon R, Poupon R. Primary biliary cirrhosis: incidence and predictive factors of cirrhosis development in ursodiol-treated patients. Gastroenterology. 2002;122:652-8 pubmed..This study provides new data about the time course of PBC under UDCA and constitutes a rationale for the design and evaluation of clinical trials aimed to assess the efficacy of drugs associated with UDCA. ..
- Binder T, Salaj P, Zima T, Vitek L. Randomized prospective comparative study of ursodeoxycholic acid and S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis of pregnancy. J Perinat Med. 2006;34:383-91 pubmed..To compare the efficacy of the ursodeoxycholic acid (UDCA) and S-adenosyl-L-methionine (SAMe) monotherapy with their combined effect on intrahepatic cholestasis of pregnancy (ICP)...
- Pares A, Rodes J. Natural history of primary biliary cirrhosis. Clin Liver Dis. 2003;7:779-94 pubmed..Prognostic models based on serial measurements of the independent predictors of poor prognosis would lead to a more accurate prediction of survival; however, they probably will not replace clinical outlook. ..
- Koulentaki M, Moscandrea J, Dimoulios P, Chatzicostas C, Kouroumalis E. Survival of anti-mitochondrial antibody-positive and -negative primary biliary cirrhosis patients on ursodeoxycholic acid treatment. Dig Dis Sci. 2004;49:1190-5 pubmed..Therefore the survival of our patients treated with ursodeoxycholic acid is higher than that predicted from the Mayo model. Early treatment may prolong survival. ..
- Zapata R, Sandoval L, Palma J, Hernandez I, Ribalta J, Reyes H, et al. Ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy. A 12-year experience. Liver Int. 2005;25:548-54 pubmed..The drug was well tolerated and no adverse effects were detected in their infants. ..
- Floreani A, Rizzotto E, Ferrara F, Carderi I, Caroli D, Blasone L, et al. Clinical course and outcome of autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome. Am J Gastroenterol. 2005;100:1516-22 pubmed..8117, p < 0.01) Patients with AIH/PSC overlap syndrome seem to benefit from immunosuppression + UDCA therapy, survival is apparently better than in "classical" PSC condition. ..
- Beuers U. Drug insight: Mechanisms and sites of action of ursodeoxycholic acid in cholestasis. Nat Clin Pract Gastroenterol Hepatol. 2006;3:318-28 pubmed..Different mechanisms of action could, therefore, contribute to the beneficial effect of UDCA under various cholestatic conditions. ..
- Poupon R, Lindor K, Pares A, Chazouilleres O, Poupon R, Heathcote E. Combined analysis of the effect of treatment with ursodeoxycholic acid on histologic progression in primary biliary cirrhosis. J Hepatol. 2003;39:12-6 pubmed..These data support the early initiation of the drug to prevent these histologic features of PBC. ..
- Talwalkar J, Souto E, Jorgensen R, Lindor K. Natural history of pruritus in primary biliary cirrhosis. Clin Gastroenterol Hepatol. 2003;1:297-302 pubmed..No significant risk reduction in developing pruritus with UDCA therapy was observed compared to placebo-treated patients. The long-term administration of rifampin for refractory pruritus is associated with occasional hepatotoxicity. ..
- Brites D. Intrahepatic cholestasis of pregnancy: changes in maternal-fetal bile acid balance and improvement by ursodeoxycholic acid. Ann Hepatol. 2002;1:20-8 pubmed..Further elucidation of the precise mechanisms of action of UDCA and its therapeutic potential in improving fetal prognosis could result in the approval of UDCA for ICP treatment. ..
- Pares A, Caballeria L, Rodes J, Bruguera M, Rodrigo L, Garcia Plaza A, et al. Long-term effects of ursodeoxycholic acid in primary biliary cirrhosis: results of a double-blind controlled multicentric trial. UDCA-Cooperative Group from the Spanish Association for the Study of the Liver. J Hepatol. 2000;32:561-6 pubmed
- Miura T, Ouchida R, Yoshikawa N, Okamoto K, Makino Y, Nakamura T, et al. Functional modulation of the glucocorticoid receptor and suppression of NF-kappaB-dependent transcription by ursodeoxycholic acid. J Biol Chem. 2001;276:47371-8 pubmed..Together with the established clinical safety of UDCA, we may propose that UDCA could be a prototypical compound for development of a novel and selective GR modifier. ..
- Funk C, Ponelle C, Scheuermann G, Pantze M. Cholestatic potential of troglitazone as a possible factor contributing to troglitazone-induced hepatotoxicity: in vivo and in vitro interaction at the canalicular bile salt export pump (Bsep) in the rat. Mol Pharmacol. 2001;59:627-35 pubmed..Such an interaction might lead to a troglitazone-induced intrahepatic cholestasis in humans as well, contributing to the formation of a troglitazone-induced liver toxicity. ..