Skip to main content

Hepatitis C and Hepatocellular Carcinoma

  • Chapter
  • First Online:
Hepatocellular Carcinoma

Part of the book series: Current Clinical Oncology ((CCO))

  • 1996 Accesses

Abstract

Hepatocellular carcinoma (HCC) usually develops in patients with chronic liver disease, those accompanied by cirrhosis in particular. Ultrasonography (US) and tumor marker tests play important roles in HCC surveillance in patients with chronic liver disease and are widely used. The primary prevention of HCV-related HCC includes strategies for the prevention of Hepatitis C virus (HCV) infection and for viral eradication. Regarding the former, novel HCV transmission in the general population has been declining in many countries, as evidenced by the lower prevalence of HCV infection among younger generations. In the recent progress of direct-acting antiviral agents (DAAs) against HCV, interferon (IFN)-free treatments are now available for compensated or decompensated cirrhosis and their effect on the prevention should be further investigated. The possibility of curative treatment depends on both tumor stage and liver function. Effective treatments for HCC include percutaneous ablation, surgical resection, and liver transplantation. Both percutaneous ablation and surgical resection provide a high rate of complete responses and are assumed to improve survival that should exceed 50 % at 5 years. Liver transplantation shows a better survival rate and is not contraindicated by advanced liver dysfunction. However, its application is limited by the scarcity of donor organs. Although short-term prognosis of HCC patients has been much improved recently due to advances in early diagnosis and treatment, long-term prognosis is as yet far from satisfactory due to frequent recurrence. Prevention of HCC recurrence remains as one of the most challenging tasks in current hepatology.

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

Access this chapter

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Similar content being viewed by others

Abbreviations

HCC:

Hepatocellular carcinoma

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

HIV:

Human immunodeficiency virus

IFN:

Interferon

UTRs:

Untranslated lesions

ALT:

Alanine aminotransferase

NS:

Nonstructural

DAA:

Direct-acting antiviral

SVR:

Sustained virologic rate

US:

Ultrasonography

CT:

Computed tomography

NASH:

Nonalcohlolic steatohepatitis

AST:

Aspartate aminotransferase

MDCT:

Multi-detector computed tomography

AFP:

Alpha fetoprotein

HGF:

Hepatocyte growth factor

IGF-1:

Insulin-like growth factor

SUV:

Standardized uptake value

QALY:

Quality-adjusted life-year

DCP:

Des-gamma-carboxyprothrombin

References

  1. Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2001;94:153–6.

    Article  CAS  PubMed  Google Scholar 

  2. Omata M, Ashcavai M, Liew CT, Peters RL. Hepatocellular carcinoma in the U.S.A., etiologic considerations. Localization of hepatitis B antigens. Gastroenterology. 1979;76:279–87.

    CAS  PubMed  Google Scholar 

  3. Sherlock S. Viruses and hepatocellular carcinoma. Gut. 1994;35:828–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Bosch FX, Ribes J, Diaz M, Cleries R. Primary liver cancer: worldwide incidence and trends. Gastroenterology. 2004;127:S5–16.

    Article  PubMed  Google Scholar 

  5. Kew MC, Yu MC, Kedda MA, Coppin A, Sarkin A, Hodkinson J. The relative roles of hepatitis B and C viruses in the etiology of hepatocellular carcinoma in Southern African blacks. Gastroenterology. 1997;112:184–7.

    Article  CAS  PubMed  Google Scholar 

  6. Pybus OG, Charleston MA, Gupta S, Rambaut A, Holmes EC, Harvey PH. The epidemic behavior of the hepatitis C virus. Science. 2001;292:2323–5.

    Article  CAS  PubMed  Google Scholar 

  7. Strader DB, Wright T, Thomas DL, Seeff LB. Diagnosis, management, and treatment of hepatitis C. Hepatology. 2004;39:1147–71.

    Article  PubMed  Google Scholar 

  8. Frank C, Mohamed MK, Strickland GT, Lavanchy D, Arthur RR, Magder LS, El Khoby T, Abdel-Wahab Y, Aly Ohn ES, Anwar W, Sallam I. The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt. Lancet. 2000;355:887–91.

    Article  CAS  PubMed  Google Scholar 

  9. Okuda K, Fujimoto I, Hanai A, Urano Y. Changing incidence of hepatocellular carcinoma in Japan. Cancer Res. 1987;47:4967–72.

    CAS  PubMed  Google Scholar 

  10. Omata M, Yoshida H, Shiratori Y. Prevention of hepatocellular carcinoma and its recurrence in chronic hepatitis C patients by interferon therapy. Clin Gastroenterol Hepatol. 2005;3:S141–3.

    Article  CAS  PubMed  Google Scholar 

  11. Tanaka Y, Hanada K, Mizokami M, Yeo AE, Shih JW, Gojobori T, Alter HJ. Inaugural article: a comparison of the molecular clock of hepatitis C virus in the United States and Japan predicts that hepatocellular carcinoma incidence in the United States will increase over the next two decades. Proc Natl Acad Sci USA. 2002;99:15584–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. El-Serag HB, Davila JA, Petersen NJ, McGlynn KA. The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update. Ann Intern Med. 2003;139:817–23.

    Article  PubMed  Google Scholar 

  13. Simmonds P. Viral heterogeneity of the hepatitis C virus. J Hepatol. 1999;31(Suppl 1):54–60.

    Article  PubMed  Google Scholar 

  14. 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;358:958–65.

    Article  CAS  PubMed  Google Scholar 

  15. 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;347:975–82.

    Article  CAS  PubMed  Google Scholar 

  16. Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, Ramadori G, Bodenheimer H Jr, Bernstein D, Rizzetto M, Zeuzem S, Pockros PJ, Lin A, Ackrill AM. Peginterferon-α2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140:346–55.

    Article  CAS  PubMed  Google Scholar 

  17. Silini E, Bono F, Cividini A, Cerino A, Bruno S, Rossi S, Belloni G, Brugnetti B, Civardi E, Salvaneschi L, et al. Differential distribution of hepatitis C virus genotypes in patients with and without liver function abnormalities. Hepatology. 1995;21:285–90.

    CAS  PubMed  Google Scholar 

  18. Feray C, Gigou M, Samuel D, Paradis V, Mishiro S, Maertens G, Reynes M, Okamoto H, Bismuth H, Brechot C. Influence of the genotypes of hepatitis C virus on the severity of recurrent liver disease after liver transplantation. Gastroenterology. 1995;108:1088–96.

    Article  CAS  PubMed  Google Scholar 

  19. Choo QL, Richman KH, Han JH, Berger K, Lee C, Dong C, Gallegos C, Coit D, Medina-Selby R, Barr PJ, et al. Genetic organization and diversity of the hepatitis C virus. Proc Natl Acad Sci USA. 1991;88:2451–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hijikata M, Kato N, Ootsuyama Y, Nakagawa M, Shimotohno K. Gene mapping of the putative structural region of the hepatitis C virus genome by in vitro processing analysis. Proc Natl Acad Sci USA. 1991;88:5547–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Grakoui A, Wychowski C, Lin C, Feinstone SM, Rice CM. Expression and identification of hepatitis C virus polyprotein cleavage products. J Virol. 1993;67:1385–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Dubuisson J. Hepatitis C virus proteins. World J Gastroenterol. 2007;13:2406–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Machida K, Cheng KT, Sung VM, Lee KJ, Levine AM, Lai MM. Hepatitis C virus infection activates the immunologic (type II) isoform of nitric oxide synthase and thereby enhances DNA damage and mutations of cellular genes. J Virol. 2004;78:8835–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Machida K, Cheng KT, Sung VM, Shimodaira S, Lindsay KL, Levine AM, Lai MY, Lai MM. Hepatitis C virus induces a mutator phenotype: enhanced mutations of immunoglobulin and protooncogenes. Proc Natl Acad Sci USA. 2004;101:4262–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Machida K, Cheng KT, Lai CK, Jeng KS, Sung VM, Lai MM. Hepatitis C virus triggers mitochondrial permeability transition with production of reactive oxygen species, leading to DNA damage and STAT3 activation. J Virol. 2006;80:7199–207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. van Pelt JF, Severi T, Crabbe T, Eetveldt AV, Verslype C, Roskams T, Fevery J. Expression of hepatitis C virus core protein impairs DNA repair in human hepatoma cells. Cancer Lett. 2004;209:197–205.

    Article  PubMed  CAS  Google Scholar 

  27. Furutani T, Hino K, Okuda M, Gondo T, Nishina S, Kitase A, Korenaga M, Xiao SY, Weinman SA, Lemon SM, Sakaida I, Okita K. Hepatic iron overload induces hepatocellular carcinoma in transgenic mice expressing the hepatitis C virus polyprotein. Gastroenterology. 2006;130:2087–98.

    Article  CAS  PubMed  Google Scholar 

  28. Lohmann V, Korner F, Koch J, Herian U, Theilmann L, Bartenschlager R. Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science. 1999;285:110–3.

    Article  CAS  PubMed  Google Scholar 

  29. Wakita T, Pietschmann T, Kato T, Date T, Miyamoto M, Zhao Z, Murthy K, Habermann A, Krausslich HG, Mizokami M, Bartenschlager R, Liang TJ. Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med. 2005;11:791–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zhong J, Gastaminza P, Cheng G, Kapadia S, Kato T, Burton DR, Wieland SF, Uprichard SL, Wakita T, Chisari FV. Robust hepatitis C virus infection in vitro. Proc Natl Acad Sci USA. 2005;102:9294–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lindenbach BD, Evans MJ, Syder AJ, Wolk B, Tellinghuisen TL, Liu CC, Maruyama T, Hynes RO, Burton DR, McKeating JA, Rice CM. Complete replication of hepatitis C virus in cell culture. Science. 2005;309:623–6.

    Article  CAS  PubMed  Google Scholar 

  32. Simonetti RG, Camma C, Fiorello F, Cottone M, Rapicetta M, Marino L, Fiorentino G, Craxi A, Ciccaglione A, Giuseppetti R, et al. Hepatitis C virus infection as a risk factor for hepatocellular carcinoma in patients with cirrhosis. A case-control study. Ann Intern Med. 1992;116:97–102.

    Article  CAS  PubMed  Google Scholar 

  33. Colombo M, de Franchis R, Del Ninno E, Sangiovanni A, De Fazio C, Tommasini M, Donato MF, Piva A, Di Carlo V, Dioguardi N. Hepatocellular carcinoma in Italian patients with cirrhosis. N Engl J Med. 1991;325:675–80.

    Article  CAS  PubMed  Google Scholar 

  34. Yoshida H, Shiratori Y, Moriyama M, Arakawa Y, Ide T, Sata M, Inoue O, Yano M, Tanaka M, Fujiyama S, Nishiguchi S, Kuroki T, Imazeki F, Yokosuka O, Kinoyama S, Yamada G, Omata M. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. IHIT study group. Inhibition of hepatocarcinogenesis by interferon therapy. Ann Intern Med. 1999;131:174–81.

    Article  CAS  PubMed  Google Scholar 

  35. Nishiguchi S, Kuroki T, Nakatani S, Morimoto H, Takeda T, Nakajima S, Shiomi S, Seki S, Kobayashi K, Otani S. Randomised trial of effects of interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet. 1995;346:1051–5.

    Article  CAS  PubMed  Google Scholar 

  36. Shiratori Y, Imazeki F, Moriyama M, Yano M, Arakawa Y, Yokosuka O, Kuroki T, Nishiguchi S, Sata M, Yamada G, Fujiyama S, Yoshida H, Omata M. Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy. Ann Intern Med. 2000;132:517–24.

    Article  CAS  PubMed  Google Scholar 

  37. Nakamoto S, Kanda T, Shirasawa H, Yokosuka O. Antiviral therapies for chronic hepatitis C virus infection with cirrhosis. World J Hepatol. 2015;7:1133–41.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Charlton M, Everson GT, Flamm SL, Kumar P, Landis C, Brown RS Jr, Fried MW, Terrault NA, O’Leary JG, Vargas HE, Kuo A, Schiff E, Sulkowski MS, Gilroy R, Watt KD, Brown K, Kwo P, Pungpapong S, Korenblat KM, Muir AJ, Teperman L, Fontana RJ, Denning J, Arterburn S, Dvory-Sobol H, Brandt-Sarif T, Pang PS, McHutchison JG, Reddy KR, Afdhal N. Ledipasvir and sofosbuvir plus ribavirin for treatment of HCV infection in patients with advanced liver disease. Gastroenterology. 2015;149:649–59.

    Article  CAS  PubMed  Google Scholar 

  39. Charlton M, Gane E, Manns MP, Brown RS Jr, Curry MP, Kwo PY, Fontana RJ, Gilroy R, Teperman L, Muir AJ, McHutchison JG, Symonds WT, Brainard D, Kirby B, Dvory-Sobol H, Denning J, Arterburn S, Samuel D, Forns X, Terrault NA. Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis C virus infection after liver transplantation. Gastroenterology. 2015;148:108–17.

    Article  CAS  PubMed  Google Scholar 

  40. Hepatitis C guidance. AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology 2015;62:932–54.

    Google Scholar 

  41. Kanda T, Imazeki F, Mikami S, Kato K, Shimada N, Yonemitsu Y, Miyauchi T, Arai M, Fujiwara K, Tsubota A, Takada N, Nishino T, Takashi M, Sugiura N, Kimura M, Fukai K, Yokosuka O. Occurrence of hepatocellular carcinoma was not a rare event during and immediately after antiviral treatment in Japanese HCV-positive patients. Oncology. 2011;80:366–72.

    Article  PubMed  Google Scholar 

  42. Shiratori Y. Different clinicopathological features of hepatitis B- and C-related hepatocellular carcinoma. J Gastroenterol Hepatol. 1996;11:942–3.

    Article  CAS  PubMed  Google Scholar 

  43. Donato F, Tagger A, Chiesa R, Ribero ML, Tomasoni V, Fasola M, Gelatti U, Portera G, Boffetta P, Nardi G. Hepatitis B and C virus infection, alcohol drinking, and hepatocellular carcinoma: a case-control study in Italy. Brescia HCC Study. Hepatology. 1997;26:579–84.

    Article  CAS  PubMed  Google Scholar 

  44. Yoshizawa H. Hepatocellular carcinoma associated with hepatitis C virus infection in Japan: projection to other countries in the foreseeable future. Oncology. 2002;62(Suppl 1):8–17.

    Article  PubMed  Google Scholar 

  45. Kiyosawa K, Umemura T, Ichijo T, Matsumoto A, Yoshizawa K, Gad A, Tanaka E. Hepatocellular carcinoma: recent trends in Japan. Gastroenterology. 2004;127:S17–26.

    Article  PubMed  Google Scholar 

  46. Beasley RP, Hwang LY, Lin CC, Chien CS. Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan. Lancet. 1981;2:1129–33.

    Article  CAS  PubMed  Google Scholar 

  47. Fattovich G, Giustina G, Schalm SW, Hadziyannis S, Sanchez-Tapias J, Almasio P, Christensen E, Krogsgaard K, Degos F, Carneiro de Moura M, et al. Occurrence of hepatocellular carcinoma and decompensation in western European patients with cirrhosis type B. The EUROHEP study group on hepatitis B virus and cirrhosis. Hepatology. 1995;21:77–82.

    CAS  PubMed  Google Scholar 

  48. Tsukuma H, Hiyama T, Tanaka S, Nakao M, Yabuuchi T, Kitamura T, Nakanishi K, Fujimoto I, Inoue A, Yamazaki H, et al. Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med. 1993;328:1797–801.

    Article  CAS  PubMed  Google Scholar 

  49. Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65–73.

    Article  CAS  PubMed  Google Scholar 

  50. Takano S, Yokosuka O, Imazeki F, Tagawa M, Omata M. Incidence of hepatocellular carcinoma in chronic hepatitis B and C: a prospective study of 251 patients. Hepatology. 1995;21:650–5.

    Article  CAS  PubMed  Google Scholar 

  51. Kato Y, Nakata K, Omagari K, Furukawa R, Kusumoto Y, Mori I, Tajima H, Tanioka H, Yano M, Nagataki S. Risk of hepatocellular carcinoma in patients with cirrhosis in Japan. Analysis of infectious hepatitis viruses. Cancer. 1994;74:2234–8.

    Article  CAS  PubMed  Google Scholar 

  52. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–76.

    Article  CAS  PubMed  Google Scholar 

  53. Liang TJ, Jeffers LJ, Reddy KR, De Medina M, Parker IT, Cheinquer H, Idrovo V, Rabassa A, Schiff ER. Viral pathogenesis of hepatocellular carcinoma in the United States. Hepatology. 1993;18:1326–33.

    CAS  PubMed  Google Scholar 

  54. Tanaka K, Hirohata T, Takeshita S, Hirohata I, Koga S, Sugimachi K, Kanematsu T, Ohryohji F, Ishibashi H. Hepatitis B virus, cigarette smoking and alcohol consumption in the development of hepatocellular carcinoma: a case-control study in Fukuoka, Japan. Int J Cancer. 1992;51:509–14.

    Article  CAS  PubMed  Google Scholar 

  55. Donato F, Tagger A, Gelatti U, Parrinello G, Boffetta P, Albertini A, Decarli A, Trevisi P, Ribero ML, Martelli C, Porru S, Nardi G. Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Am J Epidemiol. 2002;155:323–31.

    Article  CAS  PubMed  Google Scholar 

  56. Kuper H, Tzonou A, Kaklamani E, Hsieh CC, Lagiou P, Adami HO, Trichopoulos D, Stuver SO. Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma. Int J Cancer. 2000;85:498–502.

    Article  CAS  PubMed  Google Scholar 

  57. Schoniger-Hekele M, Muller C, Kutilek M, Oesterreicher C, Ferenci P, Gangl A. Hepatocellular carcinoma in Austria: aetiological and clinical characteristics at presentation. Eur J Gastroenterol Hepatol. 2000;12:941–8.

    Article  CAS  PubMed  Google Scholar 

  58. El-Serag HB, Mason AC. Risk factors for the rising rates of primary liver cancer in the United States. Arch Intern Med. 2000;160:3227–30.

    Article  CAS  PubMed  Google Scholar 

  59. Bugianesi E, Leone N, Vanni E, Marchesini G, Brunello F, Carucci P, Musso A, De Paolis P, Capussotti L, Salizzoni M, Rizzetto M. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology. 2002;123:134–40.

    Article  PubMed  Google Scholar 

  60. Shimada M, Hashimoto E, Taniai M, Hasegawa K, Okuda H, Hayashi N, Takasaki K, Ludwig J. Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis. J Hepatol. 2002;37:154–60.

    Article  PubMed  Google Scholar 

  61. Castera L, Vergniol J, Foucher J, Le Bail B, Chanteloup E, Haaser M, Darriet M, Couzigou P, De Ledinghen V. Prospective comparison of transient elastography, fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 2005;128:343–50.

    Article  PubMed  Google Scholar 

  62. Ziol M, Handra-Luca A, Kettaneh A, Christidis C, Mal F, Kazemi F, de Ledinghen V, Marcellin P, Dhumeaux D, Trinchet JC, Beaugrand M. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology. 2005;41:48–54.

    Article  PubMed  Google Scholar 

  63. Sandrin L, Fourquet B, Hasquenoph JM, Yon S, Fournier C, Mal F, Christidis C, Ziol M, Poulet B, Kazemi F, Beaugrand M, Palau R. Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol. 2003;29:1705–13.

    Article  PubMed  Google Scholar 

  64. Foucher J, Chanteloup E, Vergniol J, Castera L, Le Bail B, Adhoute X, Bertet J, Couzigou P, de Ledinghen V. Diagnosis of cirrhosis by transient elastography (fibroscan): a prospective study. Gut. 2006;55:403–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Ganne-Carrie N, Ziol M, de Ledinghen V, Douvin C, Marcellin P, Castera L, Dhumeaux D, Trinchet JC, Beaugrand M. Accuracy of liver stiffness measurement for the diagnosis of cirrhosis in patients with chronic liver diseases. Hepatology. 2006;44:1511–7.

    Article  PubMed  Google Scholar 

  66. Masuzaki R, Tateishi R, Yoshida H, Yoshida H, Sato S, Kato N, Kanai F, Sugioka Y, Ikeda H, Shiina S, Kawabe T, Omata M. Risk assessment of hepatocellular carcinoma in chronic hepatitis C patients by transient elastography. J Clin Gastroenterol. 2008;42:839–43.

    Article  PubMed  Google Scholar 

  67. Imbert-Bismut F, Ratziu V, Pieroni L, Charlotte F, Benhamou Y, Poynard T. Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet. 2001;357:1069–75.

    Article  CAS  PubMed  Google Scholar 

  68. Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, Lok AS. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38:518–26.

    Article  PubMed  Google Scholar 

  69. Taketa K. Alpha-fetoprotein: reevaluation in hepatology. Hepatology. 1990;12:1420–32.

    Article  CAS  PubMed  Google Scholar 

  70. Alpert ME, Uriel J, de Nechaud B. Alpha-1 fetoglobulin in the diagnosis of human hepatoma. N Engl J Med. 1968;278:984–6.

    Article  CAS  PubMed  Google Scholar 

  71. Collier J, Sherman M. Screening for hepatocellular carcinoma. Hepatology. 1998;27:273–8.

    Article  CAS  PubMed  Google Scholar 

  72. Sherman M, Peltekian KM, Lee C. Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North American urban population. Hepatology. 1995;22:432–8.

    CAS  PubMed  Google Scholar 

  73. Trevisani F, D’Intino PE, Morselli-Labate AM, Mazzella G, Accogli E, Caraceni P, Domenicali M, De Notariis S, Roda E, Bernardi M. Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status. J Hepatol. 2001;34:570–5.

    Article  CAS  PubMed  Google Scholar 

  74. Gambarin-Gelwan M, Wolf DC, Shapiro R, Schwartz ME, Min AD. Sensitivity of commonly available screening tests in detecting hepatocellular carcinoma in cirrhotic patients undergoing liver transplantation. Am J Gastroenterol. 2000;95:1535–8.

    Article  CAS  PubMed  Google Scholar 

  75. Nguyen MH, Garcia RT, Simpson PW, Wright TL, Keeffe EB. Racial differences in effectiveness of alpha-fetoprotein for diagnosis of hepatocellular carcinoma in hepatitis C virus cirrhosis. Hepatology. 2002;36:410–7.

    Article  CAS  PubMed  Google Scholar 

  76. Tong MJ, Blatt LM, Kao VW. Surveillance for hepatocellular carcinoma in patients with chronic viral hepatitis in the United States of America. J Gastroenterol Hepatol. 2001;16:553–9.

    Article  CAS  PubMed  Google Scholar 

  77. McMahon BJ, Bulkow L, Harpster A, Snowball M, Lanier A, Sacco F, Dunaway E, Williams J. Screening for hepatocellular carcinoma in Alaska natives infected with chronic hepatitis B: a 16-year population-based study. Hepatology. 2000;32:842–6.

    Article  CAS  PubMed  Google Scholar 

  78. Takashima T, Matsui O, Suzuki M, Ida M. Diagnosis and screening of small hepatocellular carcinomas. Comparison of radionuclide imaging, ultrasound, computed tomography, hepatic angiography, and alpha 1-fetoprotein assay. Radiology. 1982;145:635–8.

    Article  CAS  PubMed  Google Scholar 

  79. Peterson MS, Baron RL. Radiologic diagnosis of hepatocellular carcinoma. Clin Liver Dis. 2001;5:123–44.

    Article  CAS  PubMed  Google Scholar 

  80. Bennett GL, Krinsky GA, Abitbol RJ, Kim SY, Theise ND, Teperman LW. Sonographic detection of hepatocellular carcinoma and dysplastic nodules in cirrhosis: correlation of pretransplantation sonography and liver explant pathology in 200 patients. AJR Am J Roentgenol. 2002;179:75–80.

    Article  PubMed  Google Scholar 

  81. Achkar JP, Araya V, Baron RL, Marsh JW, Dvorchik I, Rakela J. Undetected hepatocellular carcinoma: clinical features and outcome after liver transplantation. Liver Transpl Surg. 1998;4:477–82.

    Article  CAS  PubMed  Google Scholar 

  82. de Ledinghen V, Laharie D, Lecesne R, Le Bail B, Winnock M, Bernard PH, Saric J, Couzigou P, Balabaud C, Bioulac-Sage P, Drouillard J. Detection of nodules in liver cirrhosis: spiral computed tomography or magnetic resonance imaging? A prospective study of 88 nodules in 34 patients. Eur J Gastroenterol Hepatol. 2002;14:159–65.

    Article  PubMed  Google Scholar 

  83. Libbrecht L, Bielen D, Verslype C, Vanbeckevoort D, Pirenne J, Nevens F, Desmet V, Roskams T. Focal lesions in cirrhotic explant livers: pathological evaluation and accuracy of pretransplantation imaging examinations. Liver Transpl. 2002;8:749–61.

    Article  PubMed  Google Scholar 

  84. Rode A, Bancel B, Douek P, Chevallier M, Vilgrain V, Picaud G, Henry L, Berger F, Bizollon T, Gaudin JL, Ducerf C. Small nodule detection in cirrhotic livers: evaluation with US, spiral CT, and MRI and correlation with pathologic examination of explanted liver. J Comput Assist Tomogr. 2001;25:327–36.

    Article  CAS  PubMed  Google Scholar 

  85. Miller WJ, Federle MP, Campbell WL. Diagnosis and staging of hepatocellular carcinoma: comparison of CT and sonography in 36 liver transplantation patients. AJR Am J Roentgenol. 1991;157:303–6.

    Article  CAS  PubMed  Google Scholar 

  86. Horigome H, Nomura T, Saso K, Itoh M, Joh T, Ohara H. Limitations of imaging diagnosis for small hepatocellular carcinoma: comparison with histological findings. J Gastroenterol Hepatol. 1999;14:559–65.

    Article  CAS  PubMed  Google Scholar 

  87. Pateron D, Ganne N, Trinchet JC, Aurousseau MH, Mal F, Meicler C, Coderc E, Reboullet P, Beaugrand M. Prospective study of screening for hepatocellular carcinoma in Caucasian patients with cirrhosis. J Hepatol. 1994;20:65–71.

    Article  CAS  PubMed  Google Scholar 

  88. Bolondi L, Sofia S, Siringo S, Gaiani S, Casali A, Zironi G, Piscaglia F, Gramantieri L, Zanetti M, Sherman M. Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost effectiveness analysis. Gut. 2001;48:251–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Cottone M, Turri M, Caltagirone M, Parisi P, Orlando A, Fiorentino G, Virdone R, Fusco G, Grasso R, Simonetti RG, et al. Screening for hepatocellular carcinoma in patients with child’s A cirrhosis: an 8-year prospective study by ultrasound and alphafetoprotein. J Hepatol. 1994;21:1029–34.

    Article  CAS  PubMed  Google Scholar 

  90. Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol. 2004;130:417–22.

    PubMed  Google Scholar 

  91. Trevisani F, Cantarini MC, Labate AM, De Notariis S, Rapaccini G, Farinati F, Del Poggio P, Di Nolfo MA, Benvegnu L, Zoli M, Borzio F, Bernardi M. Surveillance for hepatocellular carcinoma in elderly Italian patients with cirrhosis: effects on cancer staging and patient survival. Am J Gastroenterol. 2004;99:1470–6.

    Article  PubMed  Google Scholar 

  92. Pepe MS, Etzioni R, Feng Z, Potter JD, Thompson ML, Thornquist M, Winget M, Yasui Y. Phases of biomarker development for early detection of cancer. J Natl Cancer Inst. 2001;93:1054–61.

    Article  CAS  PubMed  Google Scholar 

  93. Tateishi R, Omata M. Hepatocellular carcinoma in 2011: genomics in hepatocellular carcinoma—a big step forward. Nat Rev Gastroenterol Hepatol. 2012;9:69–70.

    Article  PubMed  Google Scholar 

  94. Totoki Y, Tatsuno K, Yamamoto S, Arai Y, Hosoda F, Ishikawa S, Tsutsumi S, Sonoda K, Totsuka H, Shirakihara T, Sakamoto H, Wang L, Ojima H, Shimada K, Kosuge T, Okusaka T, Kato K, Kusuda J, Yoshida T, Aburatani H, Shibata T. High-resolution characterization of a hepatocellular carcinoma genome. Nat Genet. 2011;43:464–9.

    Article  CAS  PubMed  Google Scholar 

  95. Foley WD, Mallisee TA, Hohenwalter MD, Wilson CR, Quiroz FA, Taylor AJ. Multiphase hepatic CT with a multirow detector CT scanner. AJR Am J Roentgenol. 2000;175:679–85.

    Article  CAS  PubMed  Google Scholar 

  96. Murakami T, Kim T, Takamura M, Hori M, Takahashi S, Federle MP, Tsuda K, Osuga K, Kawata S, Nakamura H, Kudo M. Hypervascular hepatocellular carcinoma: detection with double arterial phase multi-detector row helical CT. Radiology. 2001;218:763–7.

    Article  CAS  PubMed  Google Scholar 

  97. Ichikawa T, Kitamura T, Nakajima H, Sou H, Tsukamoto T, Ikenaga S, Araki T. Hypervascular hepatocellular carcinoma: can double arterial phase imaging with multidetector CT improve tumor depiction in the cirrhotic liver? AJR Am J Roentgenol. 2002;179:751–8.

    Article  PubMed  Google Scholar 

  98. Iwata Y, Shiomi S, Sasaki N, Jomura H, Nishiguchi S, Seki S, Kawabe J, Ochi H. Clinical usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose in the diagnosis of liver tumors. Ann Nucl Med. 2000;14:121–6.

    Article  CAS  PubMed  Google Scholar 

  99. Torzilli G, Makuuchi M, Inoue K, Takayama T, Sakamoto Y, Sugawara Y, Kubota K, Zucchi A. No-mortality liver resection for hepatocellular carcinoma in cirrhotic and noncirrhotic patients: is there a way? A prospective analysis of our approach. Arch Surg. 1999;134:984–92.

    Article  CAS  PubMed  Google Scholar 

  100. Makuuchi M, Kokudo N, Arii S, Futagawa S, Kaneko S, Kawasaki S, Matsuyama Y, Okazaki M, Okita K, Omata M, Saida Y, Takayama T, Yamaoka Y. Development of evidence-based clinical guidelines for the diagnosis and treatment of hepatocellular carcinoma in Japan. Hepatol Res. 2008;38:37–51.

    Article  PubMed  Google Scholar 

  101. Sarasin FP, Giostra E, Hadengue A. Cost-effectiveness of screening for detection of small hepatocellular carcinoma in western patients with child-pugh class A cirrhosis. Am J Med. 1996;101:422–34.

    Article  CAS  PubMed  Google Scholar 

  102. Everson GT. Increasing incidence and pretransplantation screening of hepatocellular carcinoma. Liver Transpl. 2000;6:S2–10.

    Article  CAS  PubMed  Google Scholar 

  103. Sasaki Y, Yamada T, Tanaka H, Ohigashi H, Eguchi H, Yano M, Ishikawa O, Imaoka S. Risk of recurrence in a long-term follow-up after surgery in 417 patients with hepatitis B- or hepatitis C-related hepatocellular carcinoma. Ann Surg. 2006;244:771–80.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Poon RT, Fan ST, Lo CM, Liu CL, Wong J. Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation. Ann Surg. 2002;235:373–82.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Sakon M, Umeshita K, Nagano H, Eguchi H, Kishimoto S, Miyamoto A, Ohshima S, Dono K, Nakamori S, Gotoh M, Monden M. Clinical significance of hepatic resection in hepatocellular carcinoma: analysis by disease-free survival curves. Arch Surg. 2000;135:1456–9.

    Article  CAS  PubMed  Google Scholar 

  106. Kubo S, Takemura S, Sakata C, Urata Y, Uenishi T. Adjuvant therapy after curative resection for hepatocellular carcinoma associated with hepatitis virus. Liver Cancer. 2013;2:40–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Kwo PY, Mantry PS, Coakley E, Te HS, Vargas HE, Brown R Jr, Gordon F, Levitsky J, Terrault NA, Burton JR Jr, Xie W, Setze C, Badri P, Pilot-Matias T, Vilchez RA, Forns X. An interferon-free antiviral regimen for HCV after liver transplantation. N Engl J Med. 2014;371:2375–82.

    Article  PubMed  CAS  Google Scholar 

  108. Sulkowski MS, Eron JJ, Wyles D, Trinh R, Lalezari J, Wang C, Slim J, Bhatti L, Gathe J, Ruane PJ, Elion R, Bredeek F, Brennan R, Blick G, Khatri A, Gibbons K, Hu YB, Fredrick L, Schnell G, Pilot-Matias T, Tripathi R, Da Silva-Tillmann B, McGovern B, Campbell AL, Podsadecki T. Ombitasvir, paritaprevir co-dosed with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1: a randomized trial. JAMA. 2015;313:1223–31.

    Article  CAS  PubMed  Google Scholar 

  109. Hasegawa K, Takayama T, Ijichi M, Matsuyama Y, Imamura H, Sano K, Sugawara Y, Kokudo N, Makuuchi M. Uracil-tegafur as an adjuvant for hepatocellular carcinoma: a randomized trial. Hepatology. 2006;44:891–5.

    Article  CAS  PubMed  Google Scholar 

  110. Muto Y, Moriwaki H, Ninomiya M, Adachi S, Saito A, Takasaki KT, Tanaka T, Tsurumi K, Okuno M, Tomita E, Nakamura T, Kojima T. Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid, in patients with hepatocellular carcinoma. Hepatoma prevention study group. N Engl J Med. 1996;334:1561–7.

    Article  CAS  PubMed  Google Scholar 

  111. Habu D, Shiomi S, Tamori A, Takeda T, Tanaka T, Kubo S, Nishiguchi S. Role of vitamin K2 in the development of hepatocellular carcinoma in women with viral cirrhosis of the liver. JAMA. 2004;292:358–61.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Ryota Masuzaki or Masao Omata .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Masuzaki, R., Kanda, T., Yoshida, H., Kato, N., Omata, M. (2016). Hepatitis C and Hepatocellular Carcinoma. In: Carr, B. (eds) Hepatocellular Carcinoma. Current Clinical Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-34214-6_17

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-34214-6_17

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-34212-2

  • Online ISBN: 978-3-319-34214-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics