Anticholestatic effects of bezafibrate in patients with primary biliary cirrhosis treated with ursodeoxycholic acid

Hepatology

Volumn 57, Issue 5, 2013, Pages 1931-1941

  Honda, Akira ^a,b   Ikegami, Tadashi ^a   Nakamuta, Makoto ^c   Miyazaki, Teruo ^b   Iwamoto, Junichi ^a   Hirayama, Takeshi ^a   Saito, Yoshifumi ^a   Takikawa, Hajime ^d   Imawari, Michio ^e   Matsuzaki, Yasushi ^a  

^a Tokyo Medical University Ibaraki Medical Center   (Japan)

^b TOKYO MEDICAL UNIVERSITY   (Japan)

^c NATIONAL HOSPITAL ORGANIZATION   (Japan)

^d TEIKYO UNIVERSITY   (Japan)

^e SHOWA UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

4BETA HYDROXYCHOLESTEROL; 7ALPHA HYDROXY 4 CHOLESTERN 3 ONE; BEZAFIBRATE; BILE ACID; BIOLOGICAL MARKER; CHOLESTANETRIOL 26 MONOOXYGENASE; CHOLESTEROL; CHOLESTEROL 7ALPHA MONOOXYGENASE; CHOLESTEROL DERIVATIVE; CYTOCHROME P450 3A4; CYTOCHROME P450 3A5; ENZYME; IMMUNOGLOBULIN M; LIPID; MULTIDRUG RESISTANCE PROTEIN 1; MULTIDRUG RESISTANCE PROTEIN 2; MULTIDRUG RESISTANCE PROTEIN 3; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; POLYPEPTIDE; PREGNANE X RECEPTOR; SODIUM TAUROCHOLOLATE COTRANSPORTING POLYPEPTIDE; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; URSODEOXYCHOLIC ACID;

ADULT; AGED; ARTICLE; BILE ACID SYNTHESIS; BLOOD CHEMISTRY; CELL ASSAY; CHOLESTEROL BLOOD LEVEL; CLINICAL ARTICLE; CONTROLLED STUDY; DRUG EFFICACY; DRUG MECHANISM; ENZYME ACTIVITY; ENZYME ASSAY; ENZYME BLOOD LEVEL; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; GENE EXPRESSION; GENE TARGETING; HEPATOMA CELL; HISTOPATHOLOGY; HUMAN; HUMAN CELL; IMMUNOGLOBULIN BLOOD LEVEL; IN VITRO STUDY; LIPID ANALYSIS; LIPID BLOOD LEVEL; MALE; MONOTHERAPY; PRIMARY BILIARY CIRRHOSIS; PRIORITY JOURNAL; PROTEIN FUNCTION; RECEPTOR DOWN REGULATION; RECEPTOR UPREGULATION; SERUM; TREATMENT DURATION; TREATMENT RESPONSE; TRIACYLGLYCEROL BLOOD LEVEL;

ADULT; AGED; AGED, 80 AND OVER; ANTICHOLESTEREMIC AGENTS; BEZAFIBRATE; CARCINOMA, HEPATOCELLULAR; CELL LINE, TUMOR; CHOLAGOGUES AND CHOLERETICS; CYTOCHROME P-450 CYP3A; DRUG THERAPY, COMBINATION; FEMALE; HUMANS; LIPIDS; LIVER; LIVER CIRRHOSIS, BILIARY; LIVER NEOPLASMS; MALE; MIDDLE AGED; PPAR ALPHA; RECEPTORS, STEROID; TREATMENT FAILURE; TREATMENT OUTCOME; URSODEOXYCHOLIC ACID;

EID: 84876741725     PISSN: 02709139     EISSN: 15273350     Source Type: Journal    
DOI: 10.1002/hep.26018     Document Type: Article

References (55)

1. Kaplan MM, Gershwin ME. Primary biliary cirrhosis. N Engl J Med 2005; 353: 1261- 1273.
2. Ikegami T, Matsuzaki Y. Ursodeoxycholic acid: mechanism of action and novel clinical applications. Hepatol Res 2008; 38: 123- 131.
3. Poupon R, Chretien Y, Poupon RE, Ballet F, Calmus Y, Darnis F. Is ursodeoxycholic acid an effective treatment for primary biliary cirrhosis? Lancet 1987; 1: 834- 836.
4. Leuschner U, Fischer H, Kurtz W, Guldutuna S, Hubner K, Hellstern A, et al. Ursodeoxycholic acid in primary biliary cirrhosis: results of a controlled double-blind trial. Gastroenterology 1989; 97: 1268- 1274.
5. Matsuzaki Y, Tanaka N, Osuga T, Aikawa T, Shoda J, Doi M, et al. Improvement of biliary enzyme levels and itching as a result of long-term administration of ursodeoxycholic acid in primary biliary cirrhosis. Am J Gastroenterol 1990; 85: 15- 23.
6. Poupon RE, Balkau B, Eschwege E, Poupon R. A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. UDCA-PBC Study Group. N Engl J Med 1991; 324: 1548- 1554.
7. Marschall HU, Wagner M, Zollner G, Fickert P, Diczfalusy U, Gumhold J, et al. Complementary stimulation of hepatobiliary transport and detoxification systems by rifampicin and ursodeoxycholic acid in humans. Gastroenterology 2005; 129: 476- 485.
8. Corpechot C, Carrat F, Bahr A, Chretien Y, Poupon RE, Poupon R. The effect of ursodeoxycholic acid therapy on the natural course of primary biliary cirrhosis. Gastroenterology 2005; 128: 297- 303.
9. Leuschner M, Maier KP, Schlichting J, Strahl S, Herrmann G, Dahm HH, et al. Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: results of a prospective double-blind trial. Gastroenterology 1999; 117: 918- 925.
10. Rabahi N, Chretien Y, Gaouar F, Wendum D, Serfaty L, Chazouilleres O, et al. Triple therapy with ursodeoxycholic acid, budesonide and mycophenolate mofetil in patients with features of severe primary biliary cirrhosis not responding to ursodeoxycholic acid alone. Gastroenterol Clin Biol 2010; 34: 283- 287.
11. Angulo P, Jorgensen RA, Keach JC, Dickson ER, Smith C, Lindor KD. Oral budesonide in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid. HEPATOLOGY 2000; 31: 318- 323.
12. Talwalkar JA, Angulo P, Keach JC, Petz JL, Jorgensen RA, Lindor KD. Mycophenolate mofetil for the treatment of primary biliary cirrhosis in patients with an incomplete response to ursodeoxycholic acid. J Clin Gastroenterol 2005; 39: 168- 171.
13. Fiorucci S, Cipriani S, Mencarelli A, Baldelli F, Bifulco G, Zampella A. Farnesoid X receptor agonist for the treatment of liver and metabolic disorders: focus on 6-ethyl-CDCA. Mini Rev Med Chem 2011; 11: 753- 762.
14. Iwasaki S, Tsuda K, Ueta H, Aono R, Ono M, Saibara T, et al. Bezafibrate may have a beneficial effect in pre-cirrhotic primary biliary cirrhosis. Hepatol Res 1999; 16: 12- 18.
15. Itakura J, Izumi N, Nishimura Y, Inoue K, Ueda K, Nakanishi H, et al. Prospective randomized crossover trial of combination therapy with bezafibrate and UDCA for primary biliary cirrhosis. Hepatol Res 2004; 29: 216- 222.
16. Iwasaki S, Ohira H, Nishiguchi S, Zeniya M, Kaneko S, Onji M, et al. The efficacy of ursodeoxycholic acid and bezafibrate combination therapy for primary biliary cirrhosis: a prospective, multicenter study. Hepatol Res 2008; 38: 557- 564.
17. Kok T, Bloks VW, Wolters H, Havinga R, Jansen PL, Staels B, et al. Peroxisome proliferator-activated receptor alpha (PPARα)-mediated regulation of multidrug resistance 2 (Mdr2) expression and function in mice. Biochem J 2003; 369: 539- 547.
18. Willson TM, Brown PJ, Sternbach DD, Henke BR. The PPARs: from orphan receptors to drug discovery. J Med Chem 2000; 43: 527- 550.
19. Honda A, Miyazaki T, Ikegami T, Iwamoto J, Yamashita K, Numazawa M, et al. Highly sensitive and specific analysis of sterol profiles in biological samples by HPLC-ESI-MS/MS. J Steroid Biochem Mol Biol 2010; 121: 556- 564.
20. Ando M, Kaneko T, Watanabe R, Kikuchi S, Goto T, Iida T, et al. High sensitive analysis of rat serum bile acids by liquid chromatography/electrospray ionization tandem mass spectrometry. J Pharm Biomed Anal 2006; 40: 1179- 1186.
21. Honda A, Salen G, Matsuzaki Y, Batta AK, Xu G, Hirayama T, et al. Disrupted coordinate regulation of farnesoid X receptor target genes in a patient with cerebrotendinous xanthomatosis. J Lipid Res 2005; 46: 287- 296.
22. Honda A, Yoshida T, Xu G, Matsuzaki Y, Fukushima S, Tanaka N, et al. Significance of plasma 7α-hydroxy-4-cholesten-3-one and 27-hydroxycholesterol concentrations as markers for hepatic bile acid synthesis in cholesterol-fed rabbits. Metabolism 2004; 53: 42- 48.
23. Sauter G, Berr F, Beuers U, Fischer S, Paumgartner G. Serum concentrations of 7α-hydroxy-4-cholesten-3-one reflect bile acid synthesis in humans. HEPATOLOGY 1996; 24: 123- 126.
24. Lundasen T, Galman C, Angelin B, Rudling M. Circulating intestinal fibroblast growth factor 19 has a pronounced diurnal variation and modulates hepatic bile acid synthesis in man. J Intern Med 2006; 260: 530- 536.
25. Lindor KD, Lacerda MA, Jorgensen RA, DeSotel CK, Batta AK, Salen G, et al. Relationship between biliary and serum bile acids and response to ursodeoxycholic acid in patients with primary biliary cirrhosis. Am J Gastroenterol 1998; 93: 1498- 1504.
26. Hart SN, Li Y, Nakamoto K, Subileau EA, Steen D, Zhong XB. A comparison of whole genome gene expression profiles of HepaRG cells and HepG2 cells to primary human hepatocytes and human liver tissues. Drug Metab Dispos 2010; 38: 988- 994.
27. Luo G, Cunningham M, Kim S, Burn T, Lin J, Sinz M, et al. CYP3A4 induction by drugs: correlation between a pregnane X receptor reporter gene assay and CYP3A4 expression in human hepatocytes. Drug Metab Dispos 2002; 30: 795- 804.
28. Willson TM, Jones SA, Moore JT, Kliewer SA. Chemical genomics: functional analysis of orphan nuclear receptors in the regulation of bile acid metabolism. Med Res Rev 2001; 21: 513- 522.
29. Aouabdi S, Gibson G, Plant N. Transcriptional regulation of the PXR gene: identification and characterization of a functional peroxisome proliferator-activated receptor α binding site within the proximal promoter of PXR. Drug Metab Dispos 2006; 34: 138- 144.
30. Enjoji M, Yada R, Fujino T, Yoshimoto T, Yada M, Harada N, et al. The state of cholesterol metabolism in the liver of patients with primary biliary cirrhosis: the role of MDR3 expression. Hepatol Int 2009; 3: 490- 496.
31. Nakamuta M, Fujino T, Yada R, Yasutake K, Yoshimoto T, Harada N, et al. Therapeutic effect of bezafibrate against biliary damage: a study of phospholipid secretion via the PPARα-MDR3 pathway. Int J Clin Pharmacol Ther 2010; 48: 22- 28.
32. Marrapodi M, Chiang JY. Peroxisome proliferator-activated receptor a (PPARα) and agonist inhibit cholesterol 7α-hydroxylase gene (CYP7A1) transcription. J Lipid Res 2000; 41: 514- 520.
33. Post SM, Duez H, Gervois PP, Staels B, Kuipers F, Princen HM. Fibrates suppress bile acid synthesis via peroxisome proliferator-activated receptor-alpha-mediated down-regulation of cholesterol 7α-hydroxylase and sterol 27-hydroxylase expression. Arterioscler Thromb Vasc Biol 2001; 21: 1840- 1845.
34. Stedman C, Liddle C, Coulter S, Sonoda J, Alvarez JG, Evans RM, et al. Benefit of farnesoid X receptor inhibition in obstructive cholestasis. Proc Natl Acad Sci U S A 2006; 103: 11323- 11328.
35. Assem M, Schuetz EG, Leggas M, Sun D, Yasuda K, Reid G, et al. Interactions between hepatic Mrp4 and Sult2a as revealed by the constitutive androstane receptor and Mrp4 knockout mice. J Biol Chem 2004; 279: 22250- 22257.
36. Renga B, Migliorati M, Mencarelli A, Cipriani S, D'Amore C, Distrutti E, et al. Farnesoid X receptor suppresses constitutive androstane receptor activity at the multidrug resistance protein-4 promoter. Biochim Biophys Acta 2011; 1809: 157- 165.
37. Diczfalusy U, Nylen H, Elander P, Bertilsson L. 4β-Hydroxycholesterol, an endogenous marker of CYP3A4/5 activity in humans. Br J Clin Pharmacol 2011; 71: 183- 189.
38. Kajosaari LI, Backman JT, Neuvonen M, Laitila J, Neuvonen PJ. Lack of effect of bezafibrate and fenofibrate on the pharmacokinetics and pharmacodynamics of repaglinide. Br J Clin Pharmacol 2004; 58: 390- 396.
39. Faucette SR, Sueyoshi T, Smith CM, Negishi M, Lecluyse EL, Wang H. Differential regulation of hepatic CYP2B6 and CYP3A4 genes by constitutive androstane receptor but not pregnane X receptor. J Pharmacol Exp Ther 2006; 317: 1200- 1209.
40. Staudinger JL, Goodwin B, Jones SA, Hawkins-Brown D, Mackenzie KI, LaTour A, et al. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci U S A 2001; 98: 3369- 3374.
41. Xie W, Radominska-Pandya A, Shi Y, Simon CM, Nelson MC, Ong ES, et al. An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. Proc Natl Acad Sci U S A 2001; 98: 3375- 3380.
42. Synold TW, Dussault I, Forman BM. The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nat Med 2001; 7: 584- 590.
43. Kast HR, Goodwin B, Tarr PT, Jones SA, Anisfeld AM, Stoltz CM, et al. Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. J Biol Chem 2002; 277: 2908- 2915.
44. Li T, Chiang JYL. Mechanism of rifampicin and pregnane X receptor (PXR) inhibition of human cholesterol 7α-hydroxylase gene (CYP7A1) transcription. Am J Physiol 2005; 288: G74- G84.
45. De Fabiani E, Mitro N, Gilardi F, Caruso D, Galli G, Crestani M. Coordinated control of cholesterol catabolism to bile acids and of gluconeogenesis via a novel mechanism of transcription regulation linked to the fasted-to-fed cycle. J Biol Chem 2003; 278: 39124- 39132.
46. Bachs L, Pares A, Elena M, Piera C, Rodes J. Effects of long-term rifampicin administration in primary biliary cirrhosis. Gastroenterology 1992; 102: 2077- 2080.
47. Prince MI, Burt AD, Jones DE. Hepatitis and liver dysfunction with rifampicin therapy for pruritus in primary biliary cirrhosis. Gut 2002; 50: 436- 439.
48. Zimmermann C, van Waterschoot RA, Harmsen S, Maier A, Gutmann H, Schinkel AH. PXR-mediated induction of human CYP3A4 and mouse Cyp3a11 by the glucocorticoid budesonide. Eur J Pharm Sci 2009; 36: 565- 571.
49. Sorokin A, Brown JL, Thompson PD. Primary biliary cirrhosis, hyperlipidemia, and atherosclerotic risk: a systematic review. Atherosclerosis 2007; 194: 293- 299.
50. Stahlberg D, Reihner E, Rudling M, Berglund L, Einarsson K, Angelin B. Influence of bezafibrate on hepatic cholesterol metabolism in gallstone patients: reduced activity of cholesterol 7α-hydroxylase. HEPATOLOGY 1995; 21: 1025- 1030.
51. Roglans N, Vazquez-Carrera M, Alegret M, Novell F, Zambon D, Ros E, et al. Fibrates modify the expression of key factors involved in bile-acid synthesis and biliary-lipid secretion in gallstone patients. Eur J Clin Pharmacol 2004; 59: 855- 861.
52. Raedsch R, Plachky J, Wolf N, Simonis G. Biliary lipids, lithogenic index and biliary drug concentrations during etofibrate and bezafibrate treatment. Eur J Drug Metab Pharmacokinet 1995; 20: 113- 118.
53. Caroli-Bosc FX, Le Gall P, Pugliese P, Delabre B, Caroli-Bosc C, Demarquay JF, et al. Role of fibrates and HMG-CoA reductase inhibitors in gallstone formation: epidemiological study in an unselected population. Dig Dis Sci 2001; 46: 540- 544.
54. Wallace K, Cowie DE, Konstantinou DK, Hill SJ, Tjelle TE, Axon A, et al. The PXR is a drug target for chronic inflammatory liver disease. J Steroid Biochem Mol Biol 2010; 120: 137- 148.
55. Li MD, Yang X. A retrospective on nuclear receptor regulation of inflammation: lessons from GR and PPARs. PPAR Res 2011; 2011: 742785.