Skip to main content
SpringerLink
Log in

Yo Jyo Hen Shi Ko (YHK) Improves Transaminases in Nonalcoholic Steatohepatitis (NASH): A Randomized Pilot Study

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

NASH is a common condition with a rising incidence. There is progression to cirrhosis in some cases and the potential for mortality or requirement of liver transplantation. Currently, there is no approved therapy for NASH. The natural compound YHK has both anti-inflammatory and antifibrotic properties, and can lead to improvement in transaminases in viral hepatitis. Improvement in transaminases may correlate with improved histology in NASH and hence may impact on the natural history. We sought to determine the effects of YHK on NASH. We performed a randomized, double-blind, placebo-controlled pilot study to determine the effects of YHK on transaminases and on quality of life (QoL) in patients with biopsy-confirmed NASH and a persistently abnormal ALT or AST. Eight patients were randomized to YHK or placebo for 8 weeks. The ALT and AST were measured at baseline and weeks 4, 8, and 12. SF-36 surveys were serially completed. All five patients in the YHK group but none in the placebo group had a marked decrease in ALT at both week 4 and week 8 compared to baseline. After discontinuing YHK the ALT returned toward baseline at week 12. The mean decrease in ALT compared to baseline was significantly greater in the YHK group than in the placebo group at both week 4 (−42.8 ± 23.2 vs. −6.3 ± 6.7 U/L; P = 0.036) and week 8 (−45.4 ± 23.4 vs. 6.0 ± 24.6 U/L; P = 0.036). There was also a nonsignificant decrease in AST in the YHK group compared to placebo. QoL was not affected and no severe adverse events were reported. In this controlled pilot study we found the novel nutraceutical agent YHK to be effective at reducing ALT values in patients with NASH. YHK is well tolerated. Further studies are justified to assess the impact of YHK in the natural history of NASH.

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. Caldwell SH, Oelsner DH, Iezzoni JC, Hespenheide EE, Battle EH, Driscoll CJ: Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology 29:664–669, 1999

    Article  PubMed  CAS  Google Scholar 

  2. Friis-Liby I, Aldenborg F, Jerlstad P, Rundstrom K, Bjornsson E: High prevalence of metabolic complications in patients with non-alcoholic fatty liver disease. Scand J Gastroenterol 39:864–869, 2004

    Article  PubMed  CAS  Google Scholar 

  3. Neuschwander-Tetri BA, Caldwell SH: Nonalcoholic steatohepatitis: summary of an AASLD single topic conference. Hepatology 37:1202–1219, 2003

    Article  PubMed  Google Scholar 

  4. McCullough AJ: The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease. Clin Liver Dis 8:521–533, 2004

    Article  PubMed  Google Scholar 

  5. Satapathy SK, Garg S, Chauhan R, Sakhuja P, Malhotra V, Sharma BC, Sarin SK: Beneficial effects of tumor necrosis factor-α inhibition by pentoxifylline on clinical, biochemical, and metabolic parameters of patients with nonalcoholic steatohepatitis. Am J Gastroenterol 99:1946–1952, 2004

    Article  PubMed  CAS  Google Scholar 

  6. Borchers AT, Sakai S, Henderson G, Harkey MR, Keen CL, Stern JS, Terasawa K, Gershwin ME: Shosaiko-to and other Kampo (Japanese herbal) medicines: a review of their immunomodulatory activities. J Ethnopharmacol 73:1–13, 2000

    Article  PubMed  CAS  Google Scholar 

  7. Thyagarajan SP, Jayaram S, Gopalakrishnan V, Hari R, Jeyakumar P, Sripathi MS: Herbal medicines for liver diseases in India. J Gastroenterol Hepatol 17:S370–S376, 2002

    Article  PubMed  Google Scholar 

  8. Liu J, Manheimer E, Tsutani K, Gluud C: Medicinal herbs for hepatitis C virus infection: a Cochrane Hepatobiliary systematic review of randomized trials. Am J Gastroenterol 98:538–544, 2003

    Article  PubMed  Google Scholar 

  9. Marotta F, Harada M, Bertuccelli J, Rouge A, Anzulovic H, Yanaihara N, Ideo G: A nutritional approach with herbal remedy K-17,22 delays the onset of spontaneous chronic pancreatitis. J Pancreas 2(Suppl 5):350, 2001

    Google Scholar 

  10. Marotta F, Yahman-Shiled Y, Minelli E, Oliva E, Safran P, Harada M: Is there any liver anti-fibrotic effect of K-17,22? An experimental study with immunohistochemical analysis in a rat model. J Hepatol 40(Suppl 1):97, 2004

    Article  Google Scholar 

  11. Marotta F, Rouge A, Harada M, Anzulovic H, Ideo GM, Yahaihara N, Princess G, Ideo G: Beneficial effect of a controlled Chinese herbal remedy, K-17,22, in CCl4-induced liver toxicity: an in vivo and in vitro study. Biomed Res 22:167–174, 2001

    CAS  Google Scholar 

  12. Marotta F, Bertuccelli J, Albergati F, Harada M, Safran P, Yanaihara N, Ideo G: Ischemia-reperfusion liver injury : effect of a nutritional approach with K-17,22 on hepatic antioxidant defense system. Biomed Res 22:221–228, 2001

    CAS  Google Scholar 

  13. Harada M, Marotta F, Sha SH, Minelli E: YHK, a novel herbal remedy with effective antifibrotic action, in chronic liver disease: a pilot clinical study aiming to a successful integrative medicine development. First JSH Single Topic Conference, Yamanashi, Japan, November 14–15, 2002

  14. Sha S, Harada M, Yanaihara N: Effect of YHK, a new Chinese herb prescription, on serum ALT and AST levels in patients with hepatic diseases. IASL-APASL Joint Meeting 2000, New Insights of Hepatology in the 21st Century, Fukuoka, Japan, June 2–7, 2000

  15. Ware JE Jr, Sherbourne CD: The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 30:473–483, 1992

    PubMed  Google Scholar 

  16. Ludwig J, Viggiano TR, McGill DB, Oh BJ: Nonalcoholic steatohepatitis. Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 55:434–438, 1980

    PubMed  CAS  Google Scholar 

  17. Fogden E, Neuberger J: Alternative medicines and the liver. Liver Int 23:213–220, 2003

    Article  PubMed  CAS  Google Scholar 

  18. Chan P, Hong CY, Tomlinson B, Chang NC, Chen JP, Lee ST, Cheng JT: Myocardial protective effect of trilinolein: an antioxidant isolated from the medicinal plant Panax pseudoginseng. Life Sci 61:1999–2006, 1997

    Article  PubMed  CAS  Google Scholar 

  19. Chan P, Tomlinson B: Antioxidant effects of Chinese traditional medicine: focus on trilinolein isolated from the Chinese herb sanchi (Panax pseudoginseng). J Clin Pharmacol 40:457–461, 2000

    Article  PubMed  CAS  Google Scholar 

  20. Deyama T, Nishibe S, Nakazawa Y: Constituents and pharmacological effects of Eucommia and Siberian ginseng. Acta Pharmacol Sin 22:1057–1070, 2001

    PubMed  CAS  Google Scholar 

  21. Chen H, Feng R, Guo Y, Sun L, Jiang J: Hypoglycemic effects of aqueous extract of Rhizoma Polygonati Odorati in mice and rats. J Ethnopharmacol 73:225–229, 2001

    Article  Google Scholar 

  22. van Rossum TG, Vulto AG, Hop WC, Schalm SW: Glycyrrhizin-induced reduction of ALT in European patients with chronic hepatitis C. Am J Gastroenterol 96:2432–2437, 2001

    Article  PubMed  Google Scholar 

  23. Miyake K, Tango T, Ota Y, Mitamura K, Yoshiba M, Kako M, Hayashi S, Ikeda Y, Hayashida N, Iwabuchi S, Sato Y, Tomi T, Funaki N, Hashimoto N, Umeda T, Miyazaki J, Tanaka K, Endo Y, Suzuki H: Efficacy of Stronger Neo-Minophagen C compared between two doses administered three times a week on patients with chronic viral hepatitis. J Gastroenterol Hepatol 17:1198–1204, 2002

    Article  PubMed  CAS  Google Scholar 

  24. Tandon A, Tandon BN, Bhujwala RA: Clinical spectrum of acute sporadic hepatitis E and possible benefit of glycyrrhizin therapy. Hepatol Res 23:55–61, 2002

    Article  PubMed  CAS  Google Scholar 

  25. Kumada H: Long-term treatment of chronic hepatitis C with glycyrrhizin [stronger neo-minophagen C (SNMC)] for preventing liver cirrhosis and hepatocellular carcinoma. Oncology 62(Suppl 1):94–100, 2002

    Article  PubMed  CAS  Google Scholar 

  26. Miyaji C, Miyakawa R, Watanabe H, Kawamura H, Abo T: Mechanisms underlying the activation of cytotoxic function mediated by hepatic lymphocytes following the administration of glycyrrhizin. Int Immunopharmacol 2:1079–1086, 2002

    Article  PubMed  CAS  Google Scholar 

  27. Fujisawa Y, Sakamoto M, Matsushita M, Fujita T, Nishioka K: Glycyrrhizin inhibits the lytic pathway of complement—possible mechanism of its anti-inflammatory effects on liver cells in viral hepatitis. Microbiol Immunol 44:799–804, 2000

    PubMed  CAS  Google Scholar 

  28. Abe M, Akbar F, Hasebe A, Horiike N, Onji M: Glycyrrhizin enhances interleukin-10 production by liver dendritic cells in mice with hepatitis. J Gastroenterol 38:962–967, 2003

    Article  PubMed  CAS  Google Scholar 

  29. Dixon JB, Bhathal PS, Hughes NR, O'Brien PE: Nonalcoholic fatty liver disease: improvement in liver histological analysis with weight loss. Hepatology 39:1647–1654, 2004

    Article  PubMed  Google Scholar 

  30. Harrison SA, Fincke C, Helinski D, Torgerson S, Hayashi P: A pilot study of orlistat treatment in obese, non-alcoholic steatohepatitis patients. Aliment Pharmacol Ther 20:623–628, 2004

    Article  PubMed  CAS  Google Scholar 

  31. Promrat K, Lutchman G, Uwaifo GI, Freedman RJ, Soza A, Heller T: A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology 39:188–196, 2004

    Article  PubMed  CAS  Google Scholar 

  32. Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, Oliver D, Bacon BR: Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-γ ligand rosiglitazone. Hepatology 38:1008–1017, 2003

    Article  PubMed  CAS  Google Scholar 

  33. Harrison SA, Torgerson S, Hayashi P, Ward J, Schenker S: Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol 98:2485–2490, 2003

    Article  PubMed  CAS  Google Scholar 

  34. Fassio E, Alvarez E, Dominguez N, Landeira G, Longo C: Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies. Hepatology 40:820–826, 2004

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology, The University of Western Ontario, Ontario, Canada

    Nilesh Chande MD, FRCPC, Paul Adams MD, FRCPC & Paul Marotta MD, FRCPC

  2. Human Nutraceutical Research Unit, University of Guelph, Guelph, Ontario, Canada

    Maggie Laidlaw MSc

  3. London Health Sciences Centre, South Street Hospital, 375 South Street, London, Ontario, Canada, N6A 4G5

    Nilesh Chande MD, FRCPC

Authors
  1. Nilesh Chande MD, FRCPC
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maggie Laidlaw MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul Adams MD, FRCPC
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paul Marotta MD, FRCPC
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nilesh Chande MD, FRCPC.

Additional information

This study was funded by Kyotsu Jigyo, Inc., Japan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chande, N., Laidlaw, M., Adams, P. et al. Yo Jyo Hen Shi Ko (YHK) Improves Transaminases in Nonalcoholic Steatohepatitis (NASH): A Randomized Pilot Study. Dig Dis Sci 51, 1183–1189 (2006). https://doi.org/10.1007/s10620-006-8030-y

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-006-8030-y

Keywords

Search

Navigation