Skip to main content

Chemoprevention of Hepatocellular Carcinoma in Chronic Hepatitis C

  • Chapter
  • First Online:
Clinical Cancer Prevention

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 188))

Abstract

Hepatitis C virus (HCV) infection causes chronic hepatitis, which can progress to cirrhosis and hepatocellular carcinoma (HCC). The incidence of hepatocellular carcinoma in the United States tripled between 1975 and 2005, and is expected to increase further, and to remain elevated for more than 20 years. Curing hepatitis C infection in patients with cirrhosis through treatment with peginterferon and ribavirin reduces the risk of developing hepatocellular carcinoma. Several noncurative treatments also appear to reduce the risk of hepatocellular carcinoma in patients with chronic hepatitis C. Prospective studies report a reduced incidence of hepatocellular carcinoma among patients treated with a mixture of carotenoids with or without myo-inositol, with vitamin K2, or with polyprenoic acid (an acyclic retinoid). Uncontrolled and/or retrospective studies have reported beneficial effects of treatment with Sho-saiko-to, glycyrrhizin and ursodeoxycholic acid on hepatocellular carcinoma incidence. Meta-analyses of epidemiologic studies show a reduced risk of hepatocellular carcinoma among liver disease patients who drink two or more cups of coffee per day. Numerous agents prevent or reduce hepatocarcinogenesis in animal models. An ongoing Phase II clinical trial is evaluating S-adenosylmethionine (SAMe) as a potential chemopreventive agent in hepatitis C cirrhosis. Overall, these data suggest that chemoprevention of hepatocellular carcinoma in patients with chronic hepatitis C is an achievable objective.

Conflict of Interest: I receive support for clinical trials in hepatitis C treatment from Hoffmann-LaRoche, Schering Plough, Merck and Vertex. Within the past 2 years, I have served on the Advisory Board, Speaker’s Bureau, or have been a consultant for Hoffmann-LaRoche, Vertex, and/or Gilead.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Altekruse SF, McGlynn KA et al (2009) Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol 27(9):1485–1491

    Article  PubMed  Google Scholar 

  • Arase Y, Ikeda K et al (1997) The long term efficacy of glycyrrhizin in chronic hepatitis C patients. Cancer 79(8):1494–1500

    Article  PubMed  CAS  Google Scholar 

  • Backus LI, Boothroyd DB et al (2007) Predictors of response of US veterans to treatment for the hepatitis C virus. Hepatology 46(1):37–47

    Article  PubMed  CAS  Google Scholar 

  • Benten D, Keller G et al (2009) Aurora kinase inhibitor PHA-739358 suppresses growth of hepatocellular carcinoma in vitro and in a xenograft mouse model. Neoplasia 11(9):934–944

    PubMed  CAS  Google Scholar 

  • Bjelakovic G, Nikolova D et al (2004) Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet 364(9441):1219–1228

    Article  PubMed  CAS  Google Scholar 

  • Blonski W, Reddy KR (2008) Hepatitis C virus infection and hepatocellular carcinoma. Clin Liver Dis 12(3):661–674, x

    Article  PubMed  Google Scholar 

  • Borbath I, Leclercq I et al (2007) The PPARgamma agonist pioglitazone inhibits early neoplastic occurrence in the rat liver. Eur J Cancer 43(11):1755–1763

    Article  PubMed  CAS  Google Scholar 

  • Bosch FX, Ribes J et al (2005) Epidemiology of hepatocellular carcinoma. Clin Liver Dis 9(2):191–211, v

    Article  PubMed  Google Scholar 

  • Bravi F, Bosetti C et al (2007) Coffee drinking and hepatocellular carcinoma risk: a meta-analysis. Hepatology 46(2):430–435

    Article  PubMed  Google Scholar 

  • Bravi F, Bosetti C et al (2009) Coffee drinking and hepatocellular carcinoma: an update. Hepatology 50(4):1317–1318

    Article  PubMed  Google Scholar 

  • Bruix J, Sherman M (2005) Management of hepatocellular carcinoma. Hepatology 42(5):1208–1236

    Article  PubMed  Google Scholar 

  • Bruno S, Stroffolini T et al (2007) Sustained virological response to interferon-alpha is associated with improved outcome in HCV-related cirrhosis: a retrospective study. Hepatology 45(3):579–587

    Article  PubMed  CAS  Google Scholar 

  • Choo QL, Kuo G et al (1989) Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244(4902):359–362

    Article  PubMed  CAS  Google Scholar 

  • Davis GL, Balart LA et al (1989) Treatment of chronic hepatitis C with recombinant interferon alfa. A multicenter randomized, controlled trial. Hepatitis Interventional Therapy Group. N Engl J Med 321(22):1501–1506

    Article  PubMed  CAS  Google Scholar 

  • Davis GL, Alter MJ et al (2010) Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression. Gastroenterology 138(2):513–521, 521 e511–516

    Google Scholar 

  • Di Bisceglie AM, Osmack P et al (2005) Chemoprevention of hepatocellular carcinoma: use of tamoxifen in an animal model of hepatocarcinogenesis. J Lab Clin Med 145(3):134–138

    Article  PubMed  Google Scholar 

  • Di Bisceglie AM, Shiffman ML et al (2008) Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon. N Engl J Med 359(23):2429–2441

    Article  PubMed  Google Scholar 

  • Dimitroulopoulos D, Xinopoulos D et al (2007) Long acting octreotide in the treatment of advanced hepatocellular cancer and overexpression of somatostatin receptors: randomized placebo-controlled trial. World J Gastroenterol 13(23):3164–3170

    PubMed  CAS  Google Scholar 

  • El-Serag HB, Rudolph KL (2007) Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132(7):2557–2576

    Article  PubMed  CAS  Google Scholar 

  • Feinstone SM, Kapikian AZ et al (1975) Transfusion-associated hepatitis not due to viral hepatitis type A or B. N Engl J Med 292(15):767–770

    Article  PubMed  CAS  Google Scholar 

  • Freedman ND, Everhart JE et al (2009) Coffee intake is associated with lower rates of liver disease progression in chronic hepatitis C. Hepatology 50(5):1360–1369

    Article  PubMed  CAS  Google Scholar 

  • Garcea R, Daino L et al (1989) Inhibition of promotion and persistent nodule growth by S-adenosyl-L-methionine in rat liver carcinogenesis: role of remodeling and apoptosis. Cancer Res 49(7):1850–1856

    PubMed  CAS  Google Scholar 

  • George SL, Bacon BR et al (2009) Clinical, virologic, histologic, and biochemical outcomes after successful HCV therapy: a 5-year follow-up of 150 patients. Hepatology 49(3):729–738

    Article  PubMed  CAS  Google Scholar 

  • Habu D, Shiomi S et al (2004) Role of vitamin K2 in the development of hepatocellular carcinoma in women with viral cirrhosis of the liver. JAMA 292(3):358–361

    Article  PubMed  CAS  Google Scholar 

  • Hirayama C, Okumura M et al (1989) A multicenter randomized controlled clinical trial of Shosaiko-to in chronic active hepatitis. Gastroenterol Jpn 24(6):715–719

    PubMed  CAS  Google Scholar 

  • Ismail MF, Ali DA et al (2009) Chemoprevention of rat liver toxicity and carcinogenesis by Spirulina. Int J Biol Sci 5(4):377–387

    Article  PubMed  CAS  Google Scholar 

  • Kim Y, Ji SK et al (2000) Modulation of liver microsomal monooxygenase system by dietary n-6/n-3 ratios in rat hepatocarcinogenesis. Nutr Cancer 37(1):65–72

    Article  PubMed  CAS  Google Scholar 

  • Kojima S, Okuno M et al (2004) Acyclic retinoid in the chemoprevention of hepatocellular carcinoma (review). Int J Oncol 24(4):797–805

    PubMed  CAS  Google Scholar 

  • Kota J, Chivukula RR et al (2009) Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 137(6):1005–1017

    Article  PubMed  CAS  Google Scholar 

  • Kouroumalis E, Skordilis P et al (1998) Treatment of hepatocellular carcinoma with octreotide: a randomised controlled study. Gut 42(3):442–447

    Article  PubMed  CAS  Google Scholar 

  • Kuo G, Choo QL et al (1989) An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science 244(4902):362–364

    Article  PubMed  CAS  Google Scholar 

  • Kuroiwa-Trzmielina J, de Conti A et al (2009) Chemoprevention of rat hepatocarcinogenesis with histone deacetylase inhibitors: efficacy of tributyrin, a butyric acid prodrug. Int J Cancer 124(11):2520–2527

    Article  PubMed  CAS  Google Scholar 

  • La Vecchia C (2005) Coffee, liver enzymes, cirrhosis and liver cancer. J Hepatol 42(4):444–446

    Article  PubMed  Google Scholar 

  • Larsson SC, Wolk A (2007) Coffee consumption and risk of liver cancer: a meta-analysis. Gastroenterology 132(5):1740–1745

    Article  PubMed  Google Scholar 

  • Liu Q, Song Y et al (2006) A useful agent for chemoprevention of hepatocellular carcinoma? Cancer Biol Ther 5(12):1674–1676

    Article  PubMed  CAS  Google Scholar 

  • Llovet JM, Ricci S et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359(4):378–390

    Article  PubMed  CAS  Google Scholar 

  • Lok AS, Seeff LB et al (2009) Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterology 136(1):138–148

    Article  PubMed  CAS  Google Scholar 

  • Lu SC, Mato JM (2008) S-Adenosylmethionine in cell growth, apoptosis and liver cancer. J Gastroenterol Hepatol 23(Suppl 1):S73–77

    Article  PubMed  CAS  Google Scholar 

  • Lu SC, Ramani K et al (2009) S-adenosylmethionine in the chemoprevention and treatment of hepatocellular carcinoma in a rat model. Hepatology 50(2):462–471

    Article  PubMed  CAS  Google Scholar 

  • Manesis EK, Giannoulis G et al (1995) Treatment of hepatocellular carcinoma with combined suppression and inhibition of sex hormones: a randomized, controlled trial. Hepatology 21(6):1535–1542

    PubMed  CAS  Google Scholar 

  • Mann CD, Neal CP et al (2009) Phytochemicals as potential chemopreventive and chemotherapeutic agents in hepatocarcinogenesis. Eur J Cancer Prev 18(1):13–25

    Article  PubMed  CAS  Google Scholar 

  • Modi AA, Feld JJ et al (2010) Increased caffeine consumption is associated with reduced hepatic fibrosis. Hepatology 51(1):201–209

    Article  PubMed  CAS  Google Scholar 

  • Moriwaki H, Shimizu M et al (2007) Chemoprevention of liver carcinogenesis with retinoids: basic and clinical aspects. Hepatol Res 37(Suppl 2):S299–302

    Article  PubMed  CAS  Google Scholar 

  • Muto Y, Moriwaki H et al (1996) Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid, in patients with hepatocellular carcinoma. Hepatoma Prevention Study Group. N Engl J Med 334(24):1561–1567

    Article  PubMed  CAS  Google Scholar 

  • Muto Y, Moriwaki H et al (1999) Prevention of second primary tumors by an acyclic retinoid in patients with hepatocellular carcinoma. N Engl J Med 340(13):1046–1047

    Article  PubMed  CAS  Google Scholar 

  • Nishino H (2007) Prevention of hepatocellular carcinoma in chronic viral hepatitis patients with cirrhosis by carotenoid mixture. Recent Results Cancer Res 174:67–71

    Article  PubMed  CAS  Google Scholar 

  • Nishino H (2009) Phytochemicals in hepatocellular cancer prevention. Nutr Cancer 61(6):789–791

    Article  PubMed  Google Scholar 

  • Nishino H, Murakoshi M et al (2009) Cancer prevention by carotenoids. Arch Biochem Biophys 483(2):165–168

    Article  PubMed  CAS  Google Scholar 

  • Oka H, Yamamoto S et al (1995) Prospective study of chemoprevention of hepatocellular carcinoma with Sho-saiko-to (TJ-9). Cancer 76(5):743–749

    Article  PubMed  CAS  Google Scholar 

  • Parkin DM (2001) Global cancer statistics in the year 2000. Lancet Oncol 2(9):533–543

    Article  PubMed  CAS  Google Scholar 

  • Rahman KM, Sugie S et al (1999) Modulating effects of diets high in omega-3 and omega-6 fatty acids in initiation and postinitiation stages of diethylnitrosamine-induced hepatocarcinogenesis in rats. Jpn J Cancer Res 90(1):31–39

    Article  PubMed  CAS  Google Scholar 

  • Rayman MP (2005) Selenium in cancer prevention: a review of the evidence and mechanism of action. Proc Nutr Soc 64(4):527–542

    Article  PubMed  CAS  Google Scholar 

  • Ruhl CE, Everhart JE (2005a) Coffee and caffeine consumption reduce the risk of elevated serum alanine aminotransferase activity in the United States. Gastroenterology 128(1):24–32

    Article  PubMed  CAS  Google Scholar 

  • Ruhl CE, Everhart JE (2005b) Coffee and tea consumption are associated with a lower incidence of chronic liver disease in the United States. Gastroenterology 129(6):1928–1936

    Article  PubMed  Google Scholar 

  • Seeff LB (2009) The history of the “natural history” of hepatitis C (1968–2009). Liver Int 29(Suppl 1):89–99

    Article  PubMed  Google Scholar 

  • Shichiri M, Fukai N et al (2009) Rifampicin as an oral angiogenesis inhibitor targeting hepatic cancers. Cancer Res 69(11):4760–4768

    Article  PubMed  CAS  Google Scholar 

  • Shiffman ML, Morishima C et al (2009) Effect of HCV RNA suppression during peginterferon alfa-2a maintenance therapy on clinical outcomes in the Halt-C trial. Gastroenterology 50(Suppl 1):S22

    Google Scholar 

  • Shimizu M, Takai K et al (2009) Strategy and mechanism for the prevention of hepatocellular carcinoma: phosphorylated retinoid X receptor alpha is a critical target for hepatocellular carcinoma chemoprevention. Cancer Sci 100(3):369–374

    Article  PubMed  CAS  Google Scholar 

  • Takami A, Nakao S et al (1999) Successful therapy of myelodysplastic syndrome with menatetrenone, a vitamin K2 analog. Int J Hematol 69(1):24–26

    PubMed  CAS  Google Scholar 

  • Tamori A, Habu D et al (2007) Potential role of vitamin K(2) as a chemopreventive agent against hepatocellular carcinoma. Hepatol Res 37(Suppl 2):S303–307

    Article  PubMed  CAS  Google Scholar 

  • Tanaka T, Nishikawa A et al (1990) Inhibitory effects of chlorogenic acid, reserpine, polyprenoic acid (E-5166), or coffee on hepatocarcinogenesis in rats and hamsters. Basic Life Sci 52:429–440

    PubMed  CAS  Google Scholar 

  • Tarao K, Fujiyama S et al (2005) Ursodiol use is possibly associated with lower incidence of hepatocellular carcinoma in hepatitis C virus-associated liver cirrhosis. Cancer Epidemiol Biomark Prev 14(1):164–169

    CAS  Google Scholar 

  • Tatsuta M, Iishi H et al (1997) Chemoprevention by amiloride against experimental hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats. Cancer Lett 119(1):109–113

    Article  PubMed  CAS  Google Scholar 

  • Veldt BJ, Heathcote EJ et al (2007) Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Ann Intern Med 147(10):677–684

    PubMed  Google Scholar 

  • Wei W, Chua MS et al (2009) Blockade of Wnt-1 signaling leads to anti-tumor effects in hepatocellular carcinoma cells. Mol Cancer 8:76

    Article  PubMed  Google Scholar 

  • Wu T (2006) Cyclooxygenase-2 in hepatocellular carcinoma. Cancer Treat Rev 32(1):28–44

    Article  PubMed  CAS  Google Scholar 

  • Zhu B, Liu GT et al (2006) Chemoprevention of bicyclol against hepatic preneoplastic lesions. Cancer Biol Ther 5(12):1665–1673

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Timothy R. Morgan .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Berlin Heidelberg

About this chapter

Cite this chapter

Morgan, T.R. (2010). Chemoprevention of Hepatocellular Carcinoma in Chronic Hepatitis C. In: Senn, HJ., Otto, F. (eds) Clinical Cancer Prevention. Recent Results in Cancer Research, vol 188. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-10858-7_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-10858-7_7

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-10856-3

  • Online ISBN: 978-3-642-10858-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics