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Hepatitis C infection and hepatocellular carcinoma

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Abstract

Hepatitis C virus causes liver cancer by establishing chronic inflammation and proliferation of liver cells and by interacting with cell genes involved in liver cell regulation. Surveillance with abdominal ultrasound of chronically infected cirrhotic patients is the only realistic approach for hepatocellular carcinoma (HCC) treatment improvement, because it allows for detection of small, better treatable tumors. Liver transplantation is the best therapeutic option in accurately selected patients, providing 5-year survival rates of 75%. Similar figures have also been achieved in selected patients with a small HCC treated with percutaneous interstitial ablation. However, these patients remain at lifelong risk of tumor recurrence.

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References and Recommended Reading

  1. Ferlay J, Parkin DM, Pisani P: GLOBOCAN graphical package 1: Cancer incidence and mortality worldwide. Lyon, France: International Agency for Research on Cancer Press; 1998.

  2. El-Serag HB, Mason AC: Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med 1999, 340:745–750.

    Article  PubMed  CAS  Google Scholar 

  3. International Agency for Research on Cancer, ed.: In Monographs on the Evolution of Carcinogenic Risks to Humans: Hepatitis Viruses, vol 59. Geneva: World Health Organization; 1994.

  4. Kew M: Hepatitis C virus and hepatocellular carcinoma in developing and developed countries. Viral Hepat Rev 1998, 4:259–269.

    Google Scholar 

  5. Tanaka Y, Hanada K, Mizokami M, et al.: 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 U S A 2002, 99:15584–15589.

    Article  PubMed  CAS  Google Scholar 

  6. Brechot C: Molecular bases of hepatitis B- and hepatitis C-related chronic liver diseases. In The Liver: Biology and Pathology, edn 4. Edited by Arias IM, et al. Philadelphia: Lippincott, Williams & Wilkins; 2001:801–830. A comprehensive review of the molecular and cellular mechanisms involved in liver carcinogenesis during chronic infection with HCV.

  7. Laurent-Puig P, Legoix P, Bluteau O, et al.: Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis. Gastroenterology 2001, 120:1763–1773.

    Article  PubMed  CAS  Google Scholar 

  8. Koike K: Role of hepatitis viruses in multistep hepatocarcinogenesis. Dig Liver Dis 2001, 33:2–6.

    Article  PubMed  CAS  Google Scholar 

  9. Ray RB, Meyer K, Ray R: Suppression of apoptotic cell death by hepatitis C virus core protein. Virology 1996, 226:178–182.

    Article  Google Scholar 

  10. Ray RB, Steel R, Meyer K, et al.: Transcriptional repression of p53 promoter by hepatitis C virus core protein. J Biol Chem 1997, 272:10983–10986.

    Article  PubMed  CAS  Google Scholar 

  11. Park YN, Chae KJ, Kim YB, et al.: Apoptosis and proliferation in hepatocarcinogenesis related to cirrhosis. Cancer 2001, 92:2733–2738.

    Article  PubMed  CAS  Google Scholar 

  12. Tradati F, Colombo M, Mannucci PM, et al.: A prospective multicenter study of hepatocellular carcinoma in Italian hemophiliacs with chronic hepatitis C. Blood 1998, 91:1173–1177.

    PubMed  CAS  Google Scholar 

  13. Tsukuma H, Hiyama T, Tanaka S, et al.: Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med 1993, 328:1797–1801.

    Article  PubMed  CAS  Google Scholar 

  14. Takano S, Yokosuka O, Imazeki F, et al.: Incidence of hepatocellular carcinoma in chronic hepatitis B and C: a prospective study of 251 patients. Hepatology 1995, 21:650–655.

    Article  PubMed  CAS  Google Scholar 

  15. Shibata M, Morizane T, Uchida T, et al.: Irregular regeneration of hepatocytes and risk of hepatocellular carcinoma in chronic hepatitis and cirrhosis with hepatitis-C-virus infection. Lancet 1998, 351:1773–1777.

    Article  PubMed  CAS  Google Scholar 

  16. Benvegnù L, Fattovich G, Noventa V, et al.: Concurrent hepatitis B and C virus infection and risk of hepatocellular carcinoma in cirrhosis: a prospective study. Cancer 1994, 74:2442–2448.

    Article  PubMed  Google Scholar 

  17. Bruno S, Silini E, Crosignani A, et al.: Hepatitis C virus genotypes and risk of hepatocellular carcinoma in cirrhosis: a prospective study. Hepatology 1997, 25:754–758.

    Article  PubMed  CAS  Google Scholar 

  18. Romeo R, Rumi MG, Del Ninno E, Colombo M: Hepatitis C virus genotype 1b and risk of hepatocellular carcinoma. Hepatology 1997, 26:1077.

    Article  PubMed  CAS  Google Scholar 

  19. Velázquez RF, Rodríguez M, Navascués CA, et al.: Prospective analysis of risk factors for hepatocellular carcinoma in patients with liver cirrhosis. Hepatology 2003, 37:520–527.

    Article  PubMed  Google Scholar 

  20. Donato MF, Arosio E, Del Ninno E, et al.: High rates of hepatocellular carcinoma in cirrhotic patients with high liver cell proliferative activity. Hepatology 2001, 34:523–528.

    Article  PubMed  CAS  Google Scholar 

  21. Donato F, Boffetta P, Puoti M: A meta-analysis of epidemiological studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma. Int J Cancer 1998, 75:347–354.

    Article  PubMed  CAS  Google Scholar 

  22. Cacciola I, Pollicino T, Squadrito G, et al.: Occult hepatitis B virus infection in patients with chronic hepatitis C liver disease. N Engl J Med 1999, 341:22–26.

    Article  PubMed  CAS  Google Scholar 

  23. Sun CA, Wu DM, Lin CC, et al.: Incidence and cofactors of hepatitis C virus-related hepatocellular carcinoma: a prospective study of 12,008 men in Taiwan. Am J Epidemiol 2003, 157:674–682.

    Article  PubMed  Google Scholar 

  24. Tagger A, Donato F, Ribero ML, et al.: Case-control study on hepatitis C virus (HCV) as a risk factor for hepatocellular carcinoma: the role of HCV genotypes and the synergism with hepatitis B virus and alcohol. Brescia HCC Study. Int J Cancer 1999, 81:695–699.

    Article  PubMed  CAS  Google Scholar 

  25. Kubo S, Kinoshita H, Hirohashi K, et al.: High malignancy of hepatocellular carcinoma in alcoholic patients with hepatitis C virus. Surgery 1997, 121:425–429.

    Article  PubMed  CAS  Google Scholar 

  26. Yu H, Harris RE, Kapat GC, et al.: Cigarette smoking alcohol consumption and primary liver cancer. A case-control study in the USA. Int J Cancer 1988, 42:325–328.

    Article  PubMed  CAS  Google Scholar 

  27. Sharp GB, Mizuno T, Cologne JB, et al.: Hepatocellular carcinoma among atomic bomb survivors: significant interaction of radiation with hepatitis C virus infections. Int J Cancer 2003, 103:531–537.

    Article  PubMed  CAS  Google Scholar 

  28. Tsai TJ, Chau GY, Lui WY, et al.: Clinical significance of microscopic tumor venous invasion in patients with resectable hepatocellular carcinoma. Surgery 2000, 127:603–608.

    Article  PubMed  CAS  Google Scholar 

  29. Colombo M, de Franchis R, Del Ninno E, et al.: Hepatocellular carcinoma in Italian patients with cirrhosis. N Engl J Med 1991, 325:675–680.

    Article  PubMed  CAS  Google Scholar 

  30. Ebara M, Ohto M, Shinagawa T, et al.: Natural history of minute hepatocellular carcinoma smaller than three centimeters complicating cirrhosis. A study in 22 patients. Gastroenterology 1986, 90:289–298.

    PubMed  CAS  Google Scholar 

  31. Fasani P, Sangiovanni A, De Fazio C, et al.: High prevalence of multinodular hepatocellular carcinoma in patients with cirrhosis due to multiple etiological factors. Hepatology 1999, 29:1704–1707.

    Article  PubMed  CAS  Google Scholar 

  32. Kumada T, Nakano S, Takeda I, et al.: Patterns of recurrence after initial treatment in patients with small hepatocellular carcinoma. Hepatology 1997, 25:87–92.

    Article  PubMed  CAS  Google Scholar 

  33. Llovet JM, Bustamante J, Castells A, et al.: Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology 1999, 29:62–67.

    Article  PubMed  CAS  Google Scholar 

  34. Okuda H, Obata H, Motoike Y, Hisamitsu T: Clinicopathological features of hepatocellular carcinoma. Comparison of hepatitis B seropostive and seronegative patients. Hepatogastroenterology 1984, 31:64–68.

    PubMed  CAS  Google Scholar 

  35. Miyagawa S, Kawasaki S, Makuuchi M: Comparison of the characteristics of hepatocellular carcinoma between hepatitis B and C viral infection: tumor multicentricity in cirrhotic liver with hepatitis C. Hepatology 1996, 24:307–310.

    Article  PubMed  CAS  Google Scholar 

  36. Oka H, Kurioka N, Kim K, et al.: Prospective study of yearly detection of hepatocellular carcinoma in patients with cirrhosis. Hepatology 1990, 12:680–687.

    Article  PubMed  CAS  Google Scholar 

  37. Cottone M, Turri M, Caltagirone M, et al.: Screening for hepatocellular carcinoma in patients with Child’s A cirrhosis: an 8-year prospective study by ultrasound and alfafetoprotein. J Hepatol 1994, 21:1029–1034.

    Article  PubMed  CAS  Google Scholar 

  38. Bruix J, Sherman M, Llovet JM, et al.: Clinical Management of Hepatocellular Carcinoma Conclusions of the Barcelona: 2000 EASL Conference, Barcelona, September 15–17, 2000. J Hepatol 2001, 35:421–430. A conference involving eastern and western opinion leaders aimed at defining the best protocols for the clinical management of patients with HCC. The paper details the criteria for diagnosing HCC with imaging and histology and the recall policies to be implemented during surveillance for HCC.

    Article  PubMed  CAS  Google Scholar 

  39. Bolondi L, Sofia S, Siringo S, et al.: Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost effectiveness analysis. Gut 2001, 48:251–259.

    Article  PubMed  CAS  Google Scholar 

  40. Chen THH, Chen CJ, Yen MF, et al.: Ultrasound screening and risk factors for death from hepatocellular carcinoma in a high risk group in Taiwan. Int J Cancer 2002, 98:257–261.

    Article  PubMed  CAS  Google Scholar 

  41. Llovet JM, Fuster J, Bruix J, et al.: Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 1999, 20:1434–1440.

    Article  Google Scholar 

  42. Mazzaferro V, Regalia E, Doci R, et al.: Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996, 334:693–699.

    Article  PubMed  CAS  Google Scholar 

  43. Majno PE, Adam R, Bismuth H, et al.: Influence of preoperative transarterial lipiodol chemoembolization on resection or transplantation for and hepatocellular carcinoma in patients with cirrhosis. Ann Surg 1997, 226:688–703.

    Article  PubMed  CAS  Google Scholar 

  44. Predictive factors for long term prognosis after partial hepatectomy for patients with hepatocellular carcinoma in Japan. The Liver Cancer Study Group of Japan [no authors listed]. Cancer 1994, 74:2772–2780.

  45. Bruix J, Castells A, Bosch J, et al.: Surgical resection of hepatocellular carcinoma in cirrhotic patients: prognostic value of preoperative portal pressure. Gastroenterology 1996, 111:1018–1023.

    Article  PubMed  CAS  Google Scholar 

  46. Takayama T, Sekine T, Makuuchi M, et al.: Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial. Lancet 2000, 356:802–807.

    Article  PubMed  CAS  Google Scholar 

  47. Livraghi T, Bolondi L, Buscarini L, et al.: No treatment, resection and ethanol injection in hepatocellular carcinoma: a retrospective analysis of survival in 391 patients with cirrhosis. J Hepatol 1995, 22:522–526.

    Article  PubMed  CAS  Google Scholar 

  48. Muto Y, Moriwaki H, Ninomiya M, et al.: Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid, in patients with hepatocellular carcinoma. N Engl J Med 1996, 334:1561–1567.

    Article  PubMed  CAS  Google Scholar 

  49. Shiratori Y, Shiina S, Teratani T, et al.: Interferon therapy after tumor ablation improves prognosis in patients with hepatocellular carcinoma associated with hepatitis C virus. Ann Intern Med 2003, 138:299–306.

    PubMed  Google Scholar 

  50. Livraghi T, Goldberg SN, Lazzaroni S, et al.: Small hepatocellular carcinoma: treatment with radio-frequency ablation versus ethanol injection. Radiology 1999, 210:655–661.

    PubMed  CAS  Google Scholar 

  51. Llovet JM, Vilana R, Bru C, et al.: Increased risk of tumor seeding after percutaneous radiofrequency ablation for single hepatocellular carcinoma. Hepatology 2001, 33:1124–1129.

    Article  PubMed  CAS  Google Scholar 

  52. Llovet JM, Real MI, Montaña X, et al.: Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 2002, 359:1734–1739.

    Article  PubMed  Google Scholar 

  53. Cammà C, Giunta M, Andreone P, et al.: Interferon and prevention of hepatocellular carcinoma in viral cirrhosis: an evidence-based approach. J Hepatol 2001, 34:593–602.

    Article  PubMed  Google Scholar 

  54. Yoshida H, Arakawa Y, Sata M, et al.: Interferon therapy prolonged life expectancy among chronic hepatitis C patients. Gastroenterology 2002, 123:483–491. A retrospective analysis of 2889 Japanese patients with chronic hepatitis who underwent treatment with interferon alpha between 1986 and 1998. Mortality rates in the treated patients were lower than in the untreated ones. The maximum preventive effect of interferon on HCC was among patients with a sustained virologic response.

    Article  PubMed  CAS  Google Scholar 

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Colombo, M. Hepatitis C infection and hepatocellular carcinoma. Curr hepatitis rep 2, 166–172 (2003). https://doi.org/10.1007/s11901-003-0019-9

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