4-Methylumbelliferone as a Treatment for Chronic HBV/HCV

Summary

Open-label studies, anecdotal reports, and in vitro scientific research indicate that 4-methylumbelliferone (active ingredient of the dietary supplement Heparvit®) may prevent and reverse the symptoms and complications of chronic infection with hepatitis B virus (HBV)and hepatitis C virus (HCV). This effect has been observed among naïve patients as well as those who are non-responders to interferon, commonly used as first-line therapy for HBV and HCV. In order to scientifically address the efficacy of this 4-methylumbelliferone on chronic viral hepatitis, a randomized, placebo-controlled, blinded study is needed. It is hypothesized that 4-methylumbelliferone may reduce the impact and aggressiveness of HBV and HCV upon the liver, thereby slowing the progression to potentially life threatening liver diseases such as cancer and cirrhosis. This is a preliminary study designed to determine any indications under controlled conditions that may warrant further detailed clinical studies.

Timeline

Start

2005-09

Primary completion

—

Completion

2007-08

Publications

• Background 1: Epidemiology and Prevention of Vaccine-Preventable Diseases, 7th ed, Eds W. Atkinson, C. Wolfe, 2003, Department of Health and Human Services, Centers for Disease Control and Prevention.
• Background Asmuth DM, Nguyen HH, Melcher GP, Cohen SH, Pollard RB. Treatments for hepatitis B. Clin Infect Dis. 2004 Nov 1;39(9):1353-62. doi: 10.1086/425010. Epub 2004 Oct 12.
• Background Shaw T, Bowden S, Locarnini S. Chemotherapy for hepatitis B: new treatment options necessitate reappraisal of traditional endpoints. Gastroenterology. 2002 Dec;123(6):2135-40. doi: 10.1053/gast.2002.37288. No abstract available.
• Background Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med. 2001 Jul 5;345(1):41-52. doi: 10.1056/NEJM200107053450107. No abstract available.
• Background NIH Consensus Statement on Management of Hepatitis C: 2002. NIH Consens State Sci Statements. 2002 Jun 10-12;19(3):1-46.
• Background Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001 Sep 22;358(9286):958-65. doi: 10.1016/s0140-6736(01)06102-5.
• Background Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Haussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002 Sep 26;347(13):975-82. doi: 10.1056/NEJMoa020047.
• Background Pearlman BL. Hepatitis C treatment update. Am J Med. 2004 Sep 1;117(5):344-52. doi: 10.1016/j.amjmed.2004.03.024.
• Background 9: Penn State College of Medicine. Hershey, PA: 2004. Cited 2004 Dec 29. Faculty Research Expertise Database. Available from: http://fred.hmc.psu.edu/ds/retrieve/fred/meshdescriptor/D014468
• Background 10: Penn State College of Medicine. Hershey, PA: 2004. Cited 2004 Dec 29. Faculty Research Expertise Database. Available from: http://fred.hmc.psu.edu/ds/retrieve/fred/meshdescriptor/D006923
• Background Abate A, Dimartino V, Spina P, Costa PL, Lombardo C, Santini A, Del Piano M, Alimonti P. Hymecromone in the treatment of motor disorders of the bile ducts: a multicenter, double-blind, placebo-controlled clinical study. Drugs Exp Clin Res. 2001;27(5-6):223-31.
• Background 12: O'Kennedy R, Thornes RD, editors. Coumarins: Biology, Applications and Mode of Action. West Sussex, England: John Wiley & Sons; 1997. ISBN: 0-471-96997-4
• Background Muller MJ, Fenk A, Lautz HU, Selberg O, Canzler H, Balks HJ, von zur Muhlen A, Schmidt E, Schmidt FW. Energy expenditure and substrate metabolism in ethanol-induced liver cirrhosis. Am J Physiol. 1991 Mar;260(3 Pt 1):E338-44. doi: 10.1152/ajpendo.1991.260.3.E338.
• Background Fylaktakidou KC, Hadjipavlou-Litina DJ, Litinas KE, Nicolaides DN. Natural and synthetic coumarin derivatives with anti-inflammatory/ antioxidant activities. Curr Pharm Des. 2004;10(30):3813-33. doi: 10.2174/1381612043382710.
• Background Kawase M, Tanaka T, Sohara Y, Tani S, Sakagami H, Hauer H, Chatterjee SS. Structural requirements of hydroxylated coumarins for in vitro anti-Helicobacter pylori activity. In Vivo. 2003 Sep-Oct;17(5):509-12.
• Background Lacy A, O'Kennedy R. Studies on coumarins and coumarin-related compounds to determine their therapeutic role in the treatment of cancer. Curr Pharm Des. 2004;10(30):3797-811. doi: 10.2174/1381612043382693.
• Background Kudo D, Kon A, Yoshihara S, Kakizaki I, Sasaki M, Endo M, Takagaki K. Effect of a hyaluronan synthase suppressor, 4-methylumbelliferone, on B16F-10 melanoma cell adhesion and locomotion. Biochem Biophys Res Commun. 2004 Sep 3;321(4):783-7. doi: 10.1016/j.bbrc.2004.07.041.
• Background Lopez-Gonzalez JS, Prado-Garcia H, Aguilar-Cazares D, Molina-Guarneros JA, Morales-Fuentes J, Mandoki JJ. Apoptosis and cell cycle disturbances induced by coumarin and 7-hydroxycoumarin on human lung carcinoma cell lines. Lung Cancer. 2004 Mar;43(3):275-83. doi: 10.1016/j.lungcan.2003.09.005.
• Background Rilla K, Pasonen-Seppanen S, Rieppo J, Tammi M, Tammi R. The hyaluronan synthesis inhibitor 4-methylumbelliferone prevents keratinocyte activation and epidermal hyperproliferation induced by epidermal growth factor. J Invest Dermatol. 2004 Oct;123(4):708-14. doi: 10.1111/j.0022-202X.2004.23409.x.
• Background 20: Sun S, Kong LY, Zhang HQ, He SA, Niwa M. The asymmetric synthesis of linear dihydropyrano-coumarins for Alzheimer's disease. Heterocycles 2004;63:271-82.
• Salman L, Martinez L, Faddoul G, Manning C, Ali K, Salman M, Vazquez-Padron R. Hyaluronan Inhibition as a Therapeutic Target for Diabetic Kidney Disease: What Is Next? Kidney360. 2023 Jun 1;4(6):e851-e860. doi: 10.34067/KID.0000000000000126. Epub 2023 Apr 14.

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