Screening Program in High-Risk Populations

  • Ryota Masuzaki
  • Masao Omata


Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide [1–5]. The majority of patients with HCC have a background of chronic liver disease, especially chronic hepatitis due to hepatitis C virus (HCV) or hepatitis B virus (HBV) infection [6, 7]. Thus, at least some high-risk patients for HCC can be readily defined. Indeed, HCC surveillance is commonly performed as part of the standard clinical examination of patients with chronic viral hepatitis [8].


Screening Surveillance AFP Ultrasonography 


  1. 1.
    Parkin DM, Bray F, Ferlay J, Pisani P (2001) Estimating the world cancer burden: Globocan 2000. Int J Cancer 94:153–156CrossRefPubMedGoogle Scholar
  2. 2.
    Bosch FX, Ribes J, Diaz M, Cleries R (2004) Primary liver cancer: worldwide incidence and trends. Gastroenterology 127:S5–S16Google Scholar
  3. 3.
    Capocaccia R, Sant M, Berrino F, Simonetti A, Santi V, Trevisani F (2007) Hepatocellular carcinoma: trends of incidence and survival in Europe and the United States at the end of the 20th century. Am J Gastroenterol 102:1661–1670; quiz 1660, 1671CrossRefPubMedGoogle Scholar
  4. 4.
    Kiyosawa K, Umemura T, Ichijo T, Matsumoto A, Yoshizawa K, Gad A, Tanaka E (2004) Hepatocellular carcinoma: recent trends in Japan. Gastroenterology 127:S17–26Google Scholar
  5. 5.
    El-Serag HB, Davila JA, Petersen NJ, McGlynn KA (2003) The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update. Ann Intern Med 139:817–823PubMedGoogle Scholar
  6. 6.
    Yoshida H, Shiratori Y, Moriyama M, Arakawa Y, Ide T, Sata M, Inoue O, et al (1999) 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 131: 174–181PubMedGoogle Scholar
  7. 7.
    Shiratori Y (1996) Different clinicopathological features of hepatitis B- and C-related hepatocellular carcinoma. J Gastroenterol Hepatol 11:942–943CrossRefPubMedGoogle Scholar
  8. 8.
    Bruix J, Sherman M (2005) Management of hepatocellular carcinoma. Hepatology 42: 1208–1236CrossRefPubMedGoogle Scholar
  9. 9.
    Bosch FX, Ribes J, Borras J (1999) Epidemiology of primary liver cancer. Semin Liver Dis 19:271–285CrossRefPubMedGoogle Scholar
  10. 10.
    Donato F, Tagger A, Chiesa R, Ribero ML, Tomasoni V, Fasola M, Gelatti U et al (1997) Hepatitis B and C virus infection, alcohol drinking, and hepatocellular carcinoma: a case-control study in Italy. Brescia HCC Study. Hepatology 26:579–584CrossRefPubMedGoogle Scholar
  11. 11.
    Kew MC, Yu MC, Kedda MA, Coppin A, Sarkin A, Hodkinson J (1997) The relative roles of hepatitis B and C viruses in the etiology of hepatocellular carcinoma in southern African blacks. Gastroenterology 112:184–187CrossRefPubMedGoogle Scholar
  12. 12.
    Sherlock S (1994) Viruses and hepatocellular carcinoma. Gut 35:828–832CrossRefPubMedGoogle Scholar
  13. 13.
    Yoshizawa H (2002) Hepatocellular carcinoma associated with hepatitis C virus infection in Japan: projection to other countries in the foreseeable future. Oncology 62(Suppl 1):8–17CrossRefPubMedGoogle Scholar
  14. 14.
    Beasley RP, Hwang LY, Lin CC, Chien CS (1981) Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan. Lancet 2:1129–1133CrossRefPubMedGoogle Scholar
  15. 15.
    Fattovich G, Giustina G, Schalm SW, Hadziyannis S, Sanchez-Tapias J, Almasio P, Christensen E, et al (1995) 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 21:77–82PubMedGoogle Scholar
  16. 16.
    Tsukuma H, Hiyama T, Tanaka S, Nakao M, Yabuuchi T, Kitamura T, Nakanishi K et al (1993) Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med 328:1797–1801CrossRefPubMedGoogle Scholar
  17. 17.
    Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT et al (2006) Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 295: 65–73CrossRefPubMedGoogle Scholar
  18. 18.
    Takano S, Yokosuka O, Imazeki F, Tagawa M, Omata M. (1995) Incidence of hepatocellular carcinoma in chronic hepatitis B and C: a prospective study of 251 patients. Hepatology 21:650–655CrossRefPubMedGoogle Scholar
  19. 19.
    Kato Y, Nakata K, Omagari K, Furukawa R, Kusumoto Y, Mori I, Tajima H et al (1994) Risk of hepatocellular carcinoma in patients with cirrhosis in Japan. Analysis of infectious hepatitis viruses. Cancer 74:2234–2238CrossRefPubMedGoogle Scholar
  20. 20.
    Liang TJ, Jeffers LJ, Reddy KR, De Medina M, Parker IT, Cheinquer H, Idrovo V et al (1993) Viral pathogenesis of hepatocellular carcinoma in the United States. Hepatology 18: 1326–1333PubMedGoogle Scholar
  21. 21.
    Omata M, Yoshida H, Shiratori Y (2005) Prevention of hepatocellular carcinoma and its recurrence in chronic hepatitis C patients by interferon therapy. Clin Gastroenterol Hepatol 3:S141–143Google Scholar
  22. 22.
    Tanaka K, Hirohata T, Takeshita S, Hirohata I, Koga S, Sugimachi K, Kanematsu T et al (1992) Hepatitis B virus, cigarette smoking and alcohol consumption in the development of hepatocellular carcinoma: a case-control study in Fukuoka, Japan. Int J Cancer 51:509–514CrossRefPubMedGoogle Scholar
  23. 23.
    Donato F, Tagger A, Gelatti U, Parrinello G, Boffetta P, Albertini A, Decarli A et al (2002) Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Am J Epidemiol 155:323–331CrossRefPubMedGoogle Scholar
  24. 24.
    Kuper H, Tzonou A, Kaklamani E, Hsieh CC, Lagiou P, Adami HO, Trichopoulos D et al (2000) Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma. Int J Cancer 85:498–502CrossRefPubMedGoogle Scholar
  25. 25.
    Schoniger-Hekele M, Muller C, Kutilek M, Oesterreicher C, Ferenci P, Gangl A (2000) Hepatocellular carcinoma in Austria: aetiological and clinical characteristics at presentation. Eur J Gastroenterol Hepatol 12:941–948CrossRefPubMedGoogle Scholar
  26. 26.
    El-Serag HB, Mason AC (2000) Risk factors for the rising rates of primary liver cancer in the United States. Arch Intern Med 160:3227–3230CrossRefPubMedGoogle Scholar
  27. 27.
    Bugianesi E, Leone N, Vanni E, Marchesini G, Brunello F, Carucci P, Musso A et al (2002) Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 123:134–140CrossRefPubMedGoogle Scholar
  28. 28.
    Shimada M, Hashimoto E, Taniai M, Hasegawa K, Okuda H, Hayashi N, Takasaki K et al (2002) Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis. J Hepatol 37:154–160CrossRefPubMedGoogle Scholar
  29. 29.
    Castera L, Vergniol J, Foucher J, Le Bail B, Chanteloup E, Haaser M, Darriet M et al (2005) Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology 128:343–350CrossRefPubMedGoogle Scholar
  30. 30.
    Sandrin L, Fourquet B, Hasquenoph JM, Yon S, Fournier C, Mal F, Christidis C et al (2003) Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol 29:1705–1713CrossRefPubMedGoogle Scholar
  31. 31.
    Foucher J, Chanteloup E, Vergniol J, Castera L, Le Bail B, Adhoute X, Bertet J et al (2006) Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study. Gut 55: 403–408CrossRefPubMedGoogle Scholar
  32. 32.
    Imbert-Bismut F, Ratziu V, Pieroni L, Charlotte F, Benhamou Y, Poynard T (2001) Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet 357:1069–1075CrossRefPubMedGoogle Scholar
  33. 33.
    Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, Lok AS (2003) A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 38:518–526CrossRefPubMedGoogle Scholar
  34. 34.
    Taketa K (1990) Alpha-fetoprotein: reevaluation in hepatology. Hepatology 12:1420–1432CrossRefPubMedGoogle Scholar
  35. 35.
    Alpert ME, Uriel J, de Nechaud B (1968) Alpha-1 fetoglobulin in the diagnosis of human hepatoma. N Engl J Med 278:984–986CrossRefPubMedGoogle Scholar
  36. 36.
    Collier J, Sherman M (1998) Screening for hepatocellular carcinoma. Hepatology 27: 273–278CrossRefPubMedGoogle Scholar
  37. 37.
    Sherman M, Peltekian KM, Lee C (1995) Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North American urban population. Hepatology 22:432–438PubMedGoogle Scholar
  38. 38.
    Trevisani F, D’Intino PE, Morselli-Labate AM, Mazzella G, Accogli E, Caraceni P, Domenicali M et al (2001) Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status. J Hepatol 34:570–575CrossRefPubMedGoogle Scholar
  39. 39.
    Gambarin-Gelwan M, Wolf DC, Shapiro R, Schwartz ME, Min AD (2000) Sensitivity of commonly available screening tests in detecting hepatocellular carcinoma in cirrhotic patients undergoing liver transplantation. Am J Gastroenterol 95:1535–1538CrossRefPubMedGoogle Scholar
  40. 40.
    Nguyen MH, Garcia RT, Simpson PW, Wright TL, Keeffe EB (2002) Racial differences in effectiveness of alpha-fetoprotein for diagnosis of hepatocellular carcinoma in hepatitis C virus cirrhosis. Hepatology 36:410–417CrossRefPubMedGoogle Scholar
  41. 41.
    Tong MJ, Blatt LM, Kao VW (2001) Surveillance for hepatocellular carcinoma in patients with chronic viral hepatitis in the United States of America. J Gastroenterol Hepatol 16: 553–559CrossRefPubMedGoogle Scholar
  42. 42.
    McMahon BJ, Bulkow L, Harpster A, Snowball M, Lanier A, Sacco F, Dunaway E et al (2000) Screening for hepatocellular carcinoma in Alaska natives infected with chronic hepatitis B: a 16-year population-based study. Hepatology 32:842–846CrossRefPubMedGoogle Scholar
  43. 43.
    Takashima T, Matsui O, Suzuki M, Ida M (1982) Diagnosis and screening of small hepatocellular carcinomas. Comparison of radionuclide imaging, ultrasound, computed tomography, hepatic angiography, and alpha 1-fetoprotein assay. Radiology 145:635–638PubMedGoogle Scholar
  44. 44.
    Peterson MS, Baron RL (2001) Radiologic diagnosis of hepatocellular carcinoma. Clin Liver Dis 5, 123–144CrossRefPubMedGoogle Scholar
  45. 45.
    Bennett GL, Krinsky GA, Abitbol RJ, Kim SY, Theise ND, Teperman LW (2002) 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 179:75–80PubMedGoogle Scholar
  46. 46.
    Achkar JP, Araya V, Baron RL, Marsh JW, Dvorchik I, Rakela J (1998) Undetected hepatocellular carcinoma: clinical features and outcome after liver transplantation. Liver Transpl Surg 4, 477–482CrossRefPubMedGoogle Scholar
  47. 47.
    de Ledinghen V, Laharie D, Lecesne R, Le Bail B, Winnock M, Bernard PH, Saric J et al (2002) 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 14:159–165CrossRefPubMedGoogle Scholar
  48. 48.
    Libbrecht L, Bielen D, Verslype C, Vanbeckevoort D, Pirenne J, Nevens F, Desmet V et al (2002) Focal lesions in cirrhotic explant livers: pathological evaluation and accuracy of pretransplantation imaging examinations. Liver Transpl 8:749–761CrossRefPubMedGoogle Scholar
  49. 49.
    Rode A, Bancel B, Douek P, Chevallier M, Vilgrain V, Picaud G, Henry L et al (2001) 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 25:327–336CrossRefPubMedGoogle Scholar
  50. 50.
    Miller WJ, Federle MP, Campbell WL (1991) Diagnosis and staging of hepatocellular carcinoma: comparison of CT and sonography in 36 liver transplantation patients. AJR Am J Roentgenol 157:303–306PubMedGoogle Scholar
  51. 51.
    Horigome H, Nomura T, Saso K, Itoh M, Joh T, Ohara H (1999) Limitations of imaging diagnosis for small hepatocellular carcinoma: comparison with histological findings. J Gastroenterol Hepatol 14:559–565CrossRefPubMedGoogle Scholar
  52. 52.
    Pateron D, Ganne N, Trinchet JC, Aurousseau MH, Mal F, Meicler C, Coderc E et al (1994) Prospective study of screening for hepatocellular carcinoma in Caucasian patients with cirrhosis. J Hepatol 20:65–71CrossRefPubMedGoogle Scholar
  53. 53.
    Bolondi L, Sofia S, Siringo S, Gaiani S, Casali A, Zironi G, Piscaglia F et al (2001) Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost effectiveness analysis. Gut 48:251–259CrossRefPubMedGoogle Scholar
  54. 54.
    Cottone M, Turri M, Caltagirone M, Parisi P, Orlando A, Fiorentino G, Virdone R et al (1994) Screening for hepatocellular carcinoma in patients with Child’s A cirrhosis: an 8-year prospective study by ultrasound and alphafetoprotein. J Hepatol 21:1029–1034CrossRefPubMedGoogle Scholar
  55. 55.
    Bo-Heng Z, Bing-Hui Y, Zhao-You T (2004) Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol 130:417–422Google Scholar
  56. 56.
    Trevisani F, Cantarini MC, Labate AM, De Notariis S, Rapaccini G, Farinati F, Del Poggio P et al (2004) Surveillance for hepatocellular carcinoma in elderly Italian patients with cirrhosis: effects on cancer staging and patient survival. Am J Gastroenterol 99:1470–1476CrossRefPubMedGoogle Scholar
  57. 57.
    Pepe MS, Etzioni R, Feng Z, Potter JD, Thompson ML, Thornquist M, Winget M et al (2001) Phases of biomarker development for early detection of cancer. J Natl Cancer Inst 93: 1054–1061CrossRefPubMedGoogle Scholar
  58. 58.
    Foley WD, Mallisee TA, Hohenwalter MD, Wilson CR, Quiroz FA, Taylor AJ (2000) Multiphase hepatic CT with a multirow detector CT scanner. AJR Am J Roentgenol 175:679–685PubMedGoogle Scholar
  59. 59.
    Murakami T, Kim T, Takamura M, Hori M, Takahashi S, Federle MP, Tsuda K et al (2001) Hypervascular hepatocellular carcinoma: detection with double arterial phase multi-detector row helical CT. Radiology 218:763–767PubMedGoogle Scholar
  60. 60.
    Ichikawa T, Kitamura T, Nakajima H, Sou H, Tsukamoto T, Ikenaga S, Araki T (2002) Hypervascular hepatocellular carcinoma: can double arterial phase imaging with multidetector CT improve tumor depiction in the cirrhotic liver? AJR Am J Roentgenol 179: 751–758PubMedGoogle Scholar
  61. 61.
    Iwata Y, Shiomi S, Sasaki N, Jomura H, Nishiguchi S, Seki S, Kawabe J et al (2000) Clinical usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose in the diagnosis of liver tumors. Ann Nucl Med 14:121–126CrossRefPubMedGoogle Scholar
  62. 62.
    Torzilli G, Minagawa M, Takayama T, Inoue K, Hui AM, Kubota K, Ohtomo K et al (1990) Accurate preoperative evaluation of liver mass lesions without fine-needle biopsy. Hepatology 30:889–893CrossRefGoogle Scholar
  63. 63.
    Makuuchi M, Kokudo N, Arii S, Futagawa S, Kaneko S, Kawasaki S, Matsuyama Y et al (2008) Development of evidence-based clinical guidelines for the diagnosis and treatment of hepatocellular carcinoma in Japan. Hepatol Res 38:37–51CrossRefPubMedGoogle Scholar
  64. 64.
    Sarasin FP, Giostra E, Hadengue A (1996) Cost-effectiveness of screening for detection of small hepatocellular carcinoma in western patients with Child-Pugh class A cirrhosis. Am J Med 101:422–434CrossRefPubMedGoogle Scholar
  65. 65.
    Everson GT (2000) Increasing incidence and pretransplantation screening of hepatocellular carcinoma. Liver Transpl 6:S2–10Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Ryota Masuzaki
    • 1
  • Masao Omata
    • 2
  1. 1.Department of GastroenterologyThe University of TokyoTokyoJapan
  2. 2.Department of GastroenterologyUniversity of TokyoTokyoJapan

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