Skip to main content
SpringerLink
Log in

The Use of S-Adenosyl-L-Methionine in the Treatment of Cholestatic Disorders

A Meta-Analysis of Clinical Trials

  • Published:
Drug Investigation Aims and scope Submit manuscript

Summary

S-Adenosyl-L-methionine (SAMe) is a new therapeutic agent for the treatment of intrahepatic cholestasis (IHC), a syndrome that overlaps with many different types of liver diseases. To obtain a global assessment of the therapeutic efficacy of this compound, a meta-analysis of 6 controlled clinical trials of SAMe in the symptomatic treatment of IHC of liver diseases and pregnancy was carried out.

The therapeutic response to SAMe treatment for 15 to 30 days proved to be superior to placebo, as assessed by resolution of pruritus (77.6% vs 27.8%, p < 0.00001; mean odds ratio: 9.23, p < 0.001), normalisation or 50% improvement in serum total bilirubin (65.2% vs 28.6%, p < 0.00001; mean odds ratio 4.69, p < 0.001), serum conjugated bilirubin (52.3% vs 27.7%, p < 0.00001; mean odds ratio 2.52, p < 0.01), alanine aminotransferase (52.4% vs 20%, p < 0.00001; mean odds ratio 3.38, p < 0.01), and γ-glutamyl transpeptidase (42.9% vs 18.1%, p < 0.00001; mean odds ratio 3.33, p < 0.01), and alkaline phosphatase (24.1% vs 12.5%, p < 0.01; mean odds ratio 1.65).

These findings confirm that SAMe is more effective than placebo in resolving pruritus and reducing or normalising the biochemical variables of cholestasis and hepatocellular necrosis in IHC of liver diseases and pregnancy.

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

  • Adachi Y, Nanno T, Kanbe A, et al. The effects of S-adenosyl-methionine on intrahepatic cholestasis. Japanese Archives of Internal Medicine 33: 185–192, 1986

    Google Scholar 

  • Almasio P, Bortolini M, Pagliaro L, Coltorti M. Role of S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis. Drugs 40 (Suppl. 3): 111–123, 1990

    Article  PubMed  Google Scholar 

  • Arias IM. Mechanisms and consequences of ion transport in the liver. In Popper H, Schaffner F (Eds) Progress in liver diseases, pp. 145–159, Grune & Stratton, New York, 1986

    Google Scholar 

  • Bergasa NV, Jones A. Management of the pruritus of cholestasis: potential role of opiate antagonists. American Journal of Gastroenterology 86: 1404–1412, 1991

    PubMed  CAS  Google Scholar 

  • Bonfirraro G, Chieffi O, Quinti R, Tedesco R, Le Grazie C, et al. S-adenosyl-L-methionine (SAMe)-induced amelioration of intrahepatic cholestasis of pregnancy: results of an open study. Drug Investigation 2: 125–128, 1990

    Google Scholar 

  • Bortolini M, Almasio P, Bray G, et al. Retrospective multicenter survey on the prevalence of intrahepatic cholestasis (IHC) complicating chronic liver disease (CLD). Abstract. Journal of Hepatology 13: S99, 1991a

    Article  Google Scholar 

  • Bortolini M, Catalino F, Scarponi S, et al. Efficacy and safety of intravenous (IV) S-adenosylmethionine (SAMe) in the management of intrahepatic cholestasis of pregnancy (ICP). Abstract. Hepatology 14: 250A, 1991b

    Google Scholar 

  • Boyer JL. Treatment of intrahepatic cholestasis. In Rodés J, Arroyo V (Eds) Therapy in liver diseases, pp. 73–82, Ediciones Doyma, Spain, 1991

    Google Scholar 

  • Bray G, Di Padova C, Tredger JM, et al. A comparison of S-adenosylmethionine (SAMe). Rifampicin (R) and ursodeoxy-cholic acid (UDCA) in primary biliary cirrhosis (PBC): interim results. Abstract. Journal of Hepatology 13 (Suppl. 2): S101, 1991

    Article  Google Scholar 

  • Caballero Plasencia AM, Montero Garcia M, Ceballos Torres A, Ortiz Betes P, Bortolini M. Total parenteral nutrition plus S-adenosylmethionine in a case of intrahepatic cholestasis. Drug Investigation 3: 333–335, 1991

    Google Scholar 

  • Cacciatore L, Varriale A, Cozzolino G, et al. S-Adenosylmethionine (SAMe) in the treatment of pruritus in chronic liver disease. Acta Therapeutica 15: 363–371, 1989

    Google Scholar 

  • Cantoni GL. Biological methylation: selected aspects. Annual Review of Biochemistry 44: 435–451, 1975

    Article  PubMed  CAS  Google Scholar 

  • Caro LE, Bruch Igarrua E, Findor J. Cirrosis biliar primaria (CPB). Tratamiento con S-adenosyl-L-methionine (SAMe). Abstract. Acta Gastroenterologica Latina Americana 13: 161, 1987

    Google Scholar 

  • Chawla RK, Lewis FW, Kutner MH, et al. Plasma cysteine, cystine and glutathione in cirrhosis. Gastroenterology 87: 770–776, 1984

    PubMed  CAS  Google Scholar 

  • Chawla RK, Bonkovsky HL, Galambos JT. Biochemistry and pharmacology of S-adenosyl-L-methionine and rationale for its use in liver disease. Drugs 40 (Suppl. 3): 98–110, 1990

    Article  PubMed  Google Scholar 

  • Coltorti M, Bortolini M, Di Padova C. A review of the studies on the clinical use of S-adenosylmethionine (SAMe) for the symptomatic treatment of intrahepatic cholestasis. Methods and Findings in Experimental and Clinical Pharmacology 12: 69–78, 1990

    PubMed  CAS  Google Scholar 

  • Corrales F, Gimenez A, Alvarez L, et al. S-adenosyl-methionine treatment prevents CCL4-induced S-adenosyl methionine synthetase inactivation and attenuates liver injury. Hepatology 16: 1022–1027, 1992

    Article  PubMed  CAS  Google Scholar 

  • Corrales F, Pajares A, Plieg OM, et al. Effect of S-adenosylmethionine treatment on methionine intolerance in alcoholic cirrhosis. Journal of Hepatology 13: S111, 1991

    Article  Google Scholar 

  • Fleiss JL. Statistical methods for rates and proportions, 2nd ed., John Wiley & Sons, New York, 1981

    Google Scholar 

  • Frezza M, Pozzato G, Chiesa L, et al. Reversal of intrahepatic cholestasis of pregnancy in women after high dose S-adenosyl-L-methionine administration. Hepatology 4: 274–278, 1984

    Article  PubMed  CAS  Google Scholar 

  • Frezza M, Di Padova C, the Italian Study Group for SAMe in liver disease. Multicenter placebo controlled trial of intravenous and oral S-adenosylmethionine in cholestatic patients with liver disease. Hepatology 7: 1105, 1987

    Google Scholar 

  • Frezza M, Surrenti C, Manzillo G, et al. Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. Gastroenterology 99: 211–215, 1990a

    PubMed  CAS  Google Scholar 

  • Frezza M, Centini G, Cammareri G, et al. S-Adenosylmethionine for the treatment of intrahepatic cholestasis of pregnancy. Results of a controlled clinical trial. Hepato-Gastroenterology 37 (Suppl. II): 122–125, 1990b

    PubMed  Google Scholar 

  • Gerbarg ZB, Horwitz RI. Resolving conflicting clinical trials: guidelines for meta-analysis. Journal of Clinical Epidemiology 41: 503–509, 1988

    Article  PubMed  CAS  Google Scholar 

  • Giannuoli G, Tinè F, Malizia G, et al. S-Adenosylmethionine for the treatment of pruritus in compensated chronic liver disease. A pilot study. Abstract. Hepatology 6: 1110, 1986

    Google Scholar 

  • Gimenez A, Caballeria J, Pares A, et al. Effect of S-adenosylmetionine on liver fibrosis in rats. Abstract. Journal of Hepatology 13: S214, 1991

    Article  Google Scholar 

  • Jorge A, Milutin C. Acciòn del SAMe en las colestasis intrahepaticas. Abstract. Acta Gastroenterologica Latino America 17: 158, 1987

    Google Scholar 

  • Kakis C, Yousef IM. Pathogenesis of lithocholate and taurolith-ocholate-induced intrahepatic cholestasis in rats. Gastroenterology 75: 595–607, 1978

    PubMed  CAS  Google Scholar 

  • Keeffe EB, Scharschmidt BF, Blankenship NM, et al. Studies of relationships among bile flow, liver plasma membrane Na+/K+-ATPase and microviscosity in the rat. Journal of Clinical Investigation 64: 1590–1598, 1979

    Article  CAS  Google Scholar 

  • L’Abbe KA, Detsky AS, O’Rourke K. Meta-analysis in clinical research. Annals of Internal Medicine 107: 224–233, 1987

    PubMed  Google Scholar 

  • Lafuenti G, Plotti G, Nicolanti G, et al. Valutazione delie modificazioni di parametri clinici e biochimici in gravide con colestasi in terapia con S-adenosyl-L-methionine per os. Giornale Italiano Ostetricia e Ginecologia 5: 357–369, 1988

    Google Scholar 

  • Lieber CS, Casini A, DeCarli LM, et al. S-Adenosyl-L-methionine attenuates liver in the baboon. Hepatology 11: 165–172, 1990

    Article  PubMed  CAS  Google Scholar 

  • Marchesini G, Bugianesi E, Bianchi G, et al. Effect of S-adenosyl-L-Methionine administration on plasma levels of sulfur-containing aminoacids in patients with liver cirrhosis. Clinical Nutrition, in press, 1992

  • Miyai K, Price UM, Fisher MM. Bile acid metabolism in mammals. Ultrastructure studies on the intrahepatic cholestasis induced by lithocholic and chenodeoxycholic acid in the rat. Laboratory Investigation 24: 293–302, 1971

    Google Scholar 

  • Muriel P, Mourelle M. Characterization of membrane fraction lipid composition and function of cirrhotic rat liver. Role of S-adenosyl-L-methionine. Journal of Hepatology 14: 16–21, 1992

    Article  PubMed  CAS  Google Scholar 

  • Poynard T, Zourabichvili O, Hilpert G, et al. Prognostic value of serum total bilirubin/γ-glutamyl transpeptidase ratio in cirrhotic patients. Hepatology 4: 324–327, 1984

    Article  PubMed  CAS  Google Scholar 

  • Rafique S, Guardascione M, Burroughs AK, et al. S-Adenosylmethionine (SAMe) in the treatment of benign recurrent intrahepatic cholestasis (BRIC). Abstract. European Journal of Clinical Investigation 21: 156A, 1991

    Google Scholar 

  • Rafique S, Guardascione M, Osman E, et al. Reversal of extra-hepatic membrane cholesterol deposition in patients with chronic liver diseases by S-adenosylmethionine. Clinical Science 83: 353–356, 1992

    PubMed  CAS  Google Scholar 

  • Ribalta J, Reyes H, Gonzalez MC, et al. S-Adenosyl-L-methionine in the treatment of patients with intrahepatic cholestasis of pregnancy: a randomized, double-blind, placebo-controlled study with negative results. Hepatology 13: 1084–1089, 1991

    PubMed  CAS  Google Scholar 

  • Rosenthal L. Meta-analytic procedures for social research. SAGE Publications, Beverly Hills, 1984

    Google Scholar 

  • Sacks HS, Berrier J, Reitman D, et al. Meta-analysis of randomized controlled trials. New England Journal of Medicine 316: 450–455, 1987

    Article  PubMed  CAS  Google Scholar 

  • Schorr-Lesnick B, Lebovics E, Dworkin B, et al. Liver diseases unique to pregnancy. American Journal of Gastroenterology 86: 659–670, 1991

    PubMed  CAS  Google Scholar 

  • Schreiber AJ, Simon FR. Estrogen-induced cholestasis: clues to pathogenesis and treatment. Hepatology 3: 607–613, 1983

    Article  PubMed  CAS  Google Scholar 

  • Sherlock S. Cholestasis. In Sherlock S (Ed.) Diseases of the liver and biliary system, 8th ed., pp. 248–272, Blackwell Scientific Publications, Oxford, 1989

    Google Scholar 

  • Smith DJ, Gordon ER. Membrane fluidity and cholestasis. Journal of Hepatology 5: 362–365, 1987

    Article  PubMed  CAS  Google Scholar 

  • Vendemiale G, Altomare E, Trizio T, et al. Effects of oral S-adenosyl-L-methionine on hepatic glutathione in patients with liver disease. Scandinavian Journal of Gastroenterology 24: 407–415, 1989

    Article  PubMed  CAS  Google Scholar 

  • Yousef IM, Braunwell SG, Tuchweber B, et al. Effect of complete sulfatation of bile acids on bile formation in rats. Hepatology 7: 535–542, 1987

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Servizio di Gastroenterologia ed Endoscopia Digestiva, Ospedale Cattinara, Strada Fiume, 34143, Trieste, Italy

    Mario Frezza & M. Terpin

Authors
  1. Mario Frezza
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Terpin
    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

Frezza, M., Terpin, M. The Use of S-Adenosyl-L-Methionine in the Treatment of Cholestatic Disorders. Drug Invest 4 (Suppl 4), 101–108 (1992). https://doi.org/10.1007/BF03258370

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03258370

Keywords

Search

Navigation