Skip to main content
SpringerLink
Log in

Bezafibrate may attenuate biliary damage associated with chronic liver diseases accompanied by high serum biliary enzyme levels

  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Bezafibrate is a commonly used medicine for hyperlipidemia, and recently several reports have suggested the efficacy of bezafibrate for the treatment of primary biliary cirrhosis (PBC). To assess its efficacy for other liver diseases, we administered bezafibrate to patients with various categories of hepatobiliary impairment.

Methods

Bezafibrate (400 mg/day) was orally administered to 67 patients with chronic liver disease [22 with PBC, six with primary sclerosing cholangitis (PSC), 20 with chronic liver disease associated with hepatitis C virus (HCV) infection (CLD-C), seven with auto immune hepatitis (AIH), ten with alcoholic liver injury, and two with drug-induced liver injury].

Results

The levels of biliary enzymes, such as alkaline phosphatase and γ-glutamyltranspeptidase, decreased promptly and dramatically. The abnormally high level of alanine aminotransferase also showed a gradual decrease over 6 months in five of the eight PBC patients, all three PSC patients, eight of the 17 CLD-C patients, and all seven alcoholic liver injury patients. The level of immunoglobulin M showed a gradual decrease in 17 of the 22 PBC patients.

Conclusions

Bezafibrate significantly reduced the level of biliary enzymes in various chronic liver diseases and may be useful for the treatment of certain liver disease subsets.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. D Stahlberg (1992) ArticleTitleEffects of bezafibrate—a hypolipidemic drug Cardiovasc Drug Rev 10 259–79 Occurrence Handle10.1111/j.1527-3466.1992.tb00250.x

    Article  Google Scholar 

  2. CG Ericsson A Hamsten J Nilsson L Grip B Svane U de Faire (1996) ArticleTitleAngiographic assessment of effects of bezafibrate on progression of coronary artery disease in young male postinfarction patients Lancet 347 849–53 10.1016/S0140-6736(96)91343-4 Occurrence Handle10.1016/S0140-6736(96)91343-4 Occurrence Handle1:STN:280:DyaK287nslaisw%3D%3D Occurrence Handle8622389

    Article  CAS  PubMed  Google Scholar 

  3. AP Day MD Feher R Chopra PD Mayne (1993) ArticleTitleThe effect of bezafibrate treatment on serum alkaline phosphatase isozyme activities Metabolism 42 839–42 10.1016/0026-0495(93)90056-T Occurrence Handle10.1016/0026-0495(93)90056-T Occurrence Handle1:STN:280:DyaK3szkslKhtA%3D%3D Occurrence Handle8102192

    Article  CAS  PubMed  Google Scholar 

  4. S Iwasaki K Tsuda H Ueta R Aono M Ono T Saibara et al. (1999) ArticleTitleBezafibrate may have a beneficial effect in pre-cirrhotic primary biliary cirrhosis Hepatol Res 16 12–8 10.1016/S1386-6346(99)00033-9 Occurrence Handle10.1016/S1386-6346(99)00033-9

    Article  Google Scholar 

  5. T Kurihara M Furukawa M Tsuchiya M Akimoto H Ishiguro H Hashimoto et al. (2000) ArticleTitleEffect of bezafibrate in the treatment of primary biliary cirrhosis Curr Ther Res Clin Exp 61 74–82 Occurrence Handle1:CAS:528:DC%2BD3cXitVKrurY%3D

    CAS  Google Scholar 

  6. IG McFarlane InstitutionalAuthorNameInternational Autoimmune Hepatitis Group (1999) ArticleTitleInternational Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis J Hepatol 31 929–38 10.1016/S0168-8278(99)80297-9 Occurrence Handle10.1016/S0168-8278(99)80297-9 Occurrence Handle10580593

    Article  PubMed  Google Scholar 

  7. JJM Smit AH Schinkel RPJ Oude Elferink AK Groen E Wagenaar LV Deemter et al. (1993) ArticleTitleHomozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease Cell 75 451–62 10.1016/0092-8674(93)90380-9 Occurrence Handle10.1016/0092-8674(93)90380-9 Occurrence Handle1:CAS:528:DyaK2cXmtVKm Occurrence Handle8106172

    Article  CAS  PubMed  Google Scholar 

  8. B Staels W Koenig A Habib R Merval M Lebret IP Torra et al. (1998) ArticleTitleActivation of human aortic smooth-muscle cells is inhibited by PPARα but not by PPARγ activators Nature 393 790–3 10.1038/31701 Occurrence Handle10.1038/31701 Occurrence Handle1:CAS:528:DyaK1cXktl2jsbg%3D Occurrence Handle9655393

    Article  CAS  PubMed  Google Scholar 

  9. P Delerive K De Bosscher S Besnard W Vanden Berghe JM Peters FJ Gonzalez et al. (1999) ArticleTitlePeroxisome proliferator-activated receptor α negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factor NF-κB and AP-1 J Biol Chem 274 32048–54 10.1074/jbc.274.45.32048 Occurrence Handle10.1074/jbc.274.45.32048 Occurrence Handle1:CAS:528:DyaK1MXnt12jt74%3D Occurrence Handle10542237

    Article  CAS  PubMed  Google Scholar 

  10. PR Devchand H Keller JM Peters M Vazquez FJ Gonzalez W Wahli (1996) ArticleTitleThe PPARα–leukotriene B4 pathway to inflammation control Nature 384 39–43 10.1038/384039a0 Occurrence Handle10.1038/384039a0 Occurrence Handle1:CAS:528:DyaK28XmvVWrtL8%3D Occurrence Handle8900274

    Article  CAS  PubMed  Google Scholar 

  11. S Tsukamoto T Kanegae E Isobe (1996) ArticleTitleEffect of bezafibrate on ethanol oxidation in rats Alcohol Clin Exp Res 20 1599–603 10.1111/j.1530-0277.1996.tb01704.x Occurrence Handle10.1111/j.1530-0277.1996.tb01704.x Occurrence Handle1:CAS:528:DyaK2sXms1SrtQ%3D%3D Occurrence Handle8986210

    Article  CAS  PubMed  Google Scholar 

  12. KVN Menon RH Wiesner (1999) ArticleTitleEtiology and natural history of primary sclerosing cholangitis J Hepatobiliary Pancreat Surg 6 343–51 10.1007/s005340050128 Occurrence Handle10.1007/s005340050128

    Article  Google Scholar 

  13. YM Lee MM Kaplan (1999) ArticleTitleMedical treatment of primary sclerosing cholangitis J Hepatobiliary Pancreat Surg 6 361–5 10.1007/s005340050131 Occurrence Handle10.1007/s005340050131 Occurrence Handle1:STN:280:DC%2BD3c7jtFSgsw%3D%3D Occurrence Handle10664282

    Article  CAS  PubMed  Google Scholar 

  14. M Hirose M Shimamura T Nagoya (1991) ArticleTitleA controlled clinical trial evaluating cyclosporine in the treatment of primary sclerosing cholangitis (abstract) Hepatology 14 63

    Google Scholar 

  15. TA Knox MM Kaplan (1994) ArticleTitleA double-blind controlled trial of oral-pulse methotrexate therapy in the treatment of primary sclerosing cholangitis Gastroenterology 106 494–9 Occurrence Handle1:STN:280:DyaK2c7jtFanug%3D%3D Occurrence Handle8299916

    CAS  PubMed  Google Scholar 

  16. KD Lindor InstitutionalAuthorNameThe Mayo PSC-UDCA Study Group (1997) ArticleTitleUrsodiol for primary sclerosing cholangitis N Engl J Med 336 691–5 10.1056/NEJM199703063361003 Occurrence Handle10.1056/NEJM199703063361003 Occurrence Handle1:CAS:528:DyaK2sXitValtbw%3D Occurrence Handle9041099

    Article  CAS  PubMed  Google Scholar 

  17. C Degott ES Zafrani P Callard B Balkau RE Poupon R Poupon (1999) ArticleTitleHistopathological study of primary biliary cirrhosis and the effect of ursodeoxycholic acid treatment on histology progression Hepatology 29 1007–12 10.1002/hep.510290444 Occurrence Handle10.1002/hep.510290444 Occurrence Handle1:CAS:528:DyaK1MXisVKgs7s%3D Occurrence Handle10094939

    Article  CAS  PubMed  Google Scholar 

  18. DHV Thiel P Carroll KA Elmagd HR Rilo W Irish J McMichael et al. (1995) ArticleTitleTacrolimus (FK506), a treatment for primary sclerosing cholangitis: results of an open-label preliminary trial Am J Gastroenterol 90 455–9 Occurrence Handle7532912

    PubMed  Google Scholar 

  19. AE Bharucha R Jorgensen SN Lichtman NF LaRusso KD Lindor (2000) ArticleTitleA pilot study of pentoxifylline for the treatment of primary sclerosing cholangitis Am J Gastroenterol 95 2338–42 10.1111/j.1572-0241.2000.02324.x Occurrence Handle10.1111/j.1572-0241.2000.02324.x Occurrence Handle1:CAS:528:DC%2BD3cXntFCmtrc%3D Occurrence Handle11007239

    Article  CAS  PubMed  Google Scholar 

  20. A Stiehl G Rudolph P Sauer C Benz W Stremmel S Walker et al. (1997) ArticleTitleEfficacy of ursodeoxycholic acid and endoscopic dilation of major duct stenoses in primary sclerosing cholangitis. An 8-year prospective study J Hepatol 26 560–6 10.1016/S0168-8278(97)80421-7 Occurrence Handle10.1016/S0168-8278(97)80421-7 Occurrence Handle1:CAS:528:DyaK2sXitlOltbY%3D Occurrence Handle9075663

    Article  CAS  PubMed  Google Scholar 

  21. RH Wiesner PM Grambsch ER Dickson J Ludwig RL MacCarty EB Hunter et al. (1989) ArticleTitlePrimary sclerosing cholangitis: natural history, prognostic factors and survival analysis Hepatology 10 430–6 Occurrence Handle10.1002/hep.1840100406 Occurrence Handle1:STN:280:DyaL1MznvFShuw%3D%3D Occurrence Handle2777204

    Article  CAS  PubMed  Google Scholar 

  22. MK Porayko RH Wiesner NF LaRusso J Ludwig RL MacCarty BL Steiner et al. (1990) ArticleTitlePatients with asymptomatic primary sclerosing cholangitis frequently have progressive disease Gastroenterology 98 1594–602 Occurrence Handle1:STN:280:DyaK3c3kvFKmtg%3D%3D Occurrence Handle2338198

    CAS  PubMed  Google Scholar 

  23. H Takikawa (1999) ArticleTitleRecent status of primary sclerosing cholangitis in Japan J Hepatobiliary Pancreat Surg 6 352–5 10.1007/s005340050129 Occurrence Handle10.1007/s005340050129 Occurrence Handle1:STN:280:DC%2BD3c7jtFShuw%3D%3D Occurrence Handle10664280

    Article  CAS  PubMed  Google Scholar 

  24. RE Poupon E Eschwege R Poupon InstitutionalAuthorNameUDCA-PBC Study Group (1990) ArticleTitleUrsodeoxycholic acid for the treatment of primary biliary cirrhosis, interim analysis of a double-blind multicentre randomised trial J Hepatol 11 16–21 10.1016/0168-8278(90)90265-S Occurrence Handle10.1016/0168-8278(90)90265-S Occurrence Handle1:STN:280:DyaK3cznsFyksQ%3D%3D Occurrence Handle1975819

    Article  CAS  PubMed  Google Scholar 

  25. E Rolandi R Franceschini A Cataldi V Cicchetti L Carati T Barreca (1991) ArticleTitleEffects of ursodeoxycholic acid (UDCA) on serum liver damage indices in patients with chronic active hepatitis A double-blind controlled study Eur J Pharmacol 40 473–6 10.1007/BF00315225 Occurrence Handle10.1007/BF00315225 Occurrence Handle1:STN:280:DyaK3MzlslSntA%3D%3D

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, 5-53 Fudegasaki-cho, Tennoji-ku, Osaka, 543-8555, Japan

    Ryuichi Kita, Toru Kimura, Yukio Osaki & Naomi Tomono

  2. Takamatsu Clinic, Osaka, Japan

    Seigo Takamatsu

  3. Department of Gastroenterology, Shizuoka General Hospital, Shizuoka, Japan

    Hiroyuki Kokuryu

Authors
  1. Ryuichi Kita
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seigo Takamatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Toru Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiroyuki Kokuryu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yukio Osaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Naomi Tomono
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kita, R., Takamatsu, S., Kimura, T. et al. Bezafibrate may attenuate biliary damage associated with chronic liver diseases accompanied by high serum biliary enzyme levels. J Gastroenterol 41, 686–692 (2006). https://doi.org/10.1007/s00535-006-1831-0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-006-1831-0

Key words

Search

Navigation