Skip to main content
SpringerLink
Log in

Clinical Features and Diagnostic Evaluation of Hepatocellular Carcinoma

  • Chapter
Hepatocellular Cancer

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

  • 630 Accesses

Abstract

The diagnosis of hepatocellular carcinoma (HCC) can be difficult and often requires the use of serum markers, one or more imaging methods, and histological confirmation. HCC frequently is diagnosed late in its course because of the absence of pathognomonic symptoms and the liver’s large functional reserve (1). As a result, many patients have untreatable disease when first diagnosed. The clinical presentation generally varies in different parts of the world. Many patients with HCC related to chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection in high-incidence locations, for example, in sub-Saharan Africa and in Asia, have severe hepatic decompensation at presentation. However, the common presentation in low-incidence areas such as the United States and other Western countries may follow routine laboratory screening for HCC before symptoms are prominent (2), because approx 40% of patients are asymptomatic at the time of diagnosis (3).

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Kew MC, Dos Santos HA, Sherlock S. Diagnosis of primary cancer of the liver. Br Med J 1971;4:408–411.

    PubMed  CAS  Google Scholar 

  2. Craig JR. Tumors of the liver. In: Hepatology: A Textbook of Liver Disease (Zakim D, Boyer TD, eds.), WB Saunders, Philadelphia, 2003, pp. 1355–1370.

    Google Scholar 

  3. Aguayo A, Patt YZ. Liver cancer [review]. Clin Liver Dis 2001;5:479–507.

    Article  PubMed  CAS  Google Scholar 

  4. Trevisani F, D’Intino PE, Grazi GL, Caraceni P, Gasbarrini A, Colantoni A, et al. Clinical and pathologic features of hepatocellular carcinoma in young and older Italian patients. Cancer 1996;77:2223–2232.

    Article  PubMed  CAS  Google Scholar 

  5. Johnson PJ. Malignant tumors of the liver. In: Comprehensive Clinical Hepatology (O’Grady JG, Lake JR, Howdle PD, eds.), Harcourt, London, 2000, pp. 25.1–25.18.

    Google Scholar 

  6. Kew MC. Clinical manifestations and paraneoplastic syndromes of hepatocellular carcinoma. In: Neoplasms of the Liver (Okuda K, Ishak KG, eds.), Springer-Verlag, Tokyo, 1987, p. 199.

    Google Scholar 

  7. Kew MC. Hepatic tumors and cysts. In: Gastrointestinal and Liver Disease (Feldman M, Friedman LS, Sleisenger MH, eds.) WB Saunders, Philadelphia, 2002, pp. 1577–1602.

    Google Scholar 

  8. Chearanai O, Plengvanit U, Asavanich C, Damrongsak D, Sindhvananda K, Boonyapisit S. Spontaneous rupture of primary hepatoma: report of 63 cases with particular reference to the pathogenesis and rationale for treatment by hepatic artery ligation. Cancer 1983;51:1532–1536.

    Article  PubMed  CAS  Google Scholar 

  9. Zapf J, Futo E, Peter M, Froesch ER. Can “big” insulin-like growth factor II in serum of tumor patients account for the development of extrapancreatic tumor hypoglycemia? J Clin Investigation 1992;90:2574–2584.

    CAS  Google Scholar 

  10. Kew MC, Fisher JW. Serum erythropoietin concentrations in patients with hepatocellular carcinoma. Cancer 1986;58:2485–2488.

    Article  PubMed  CAS  Google Scholar 

  11. Yen TC, Hwang SJ, Wang CC, Lee SD, Yeh SH. Hypercalcemia and parathyroid hormonerelated protein in hepatocellular carcinoma. Liver 1993;13:311–315.

    PubMed  CAS  Google Scholar 

  12. Kew MC, Leckie BJ, Greeff MC. Arterial hypertension as a paraneoplastic phenomenon in hepatocellular carcinoma. Arch Intern Med 1989;149:2111–2113.

    Article  PubMed  CAS  Google Scholar 

  13. Kew MC, Kirschner MA, Abrahams GE, Katz M. Mechanism of feminization in primary liver cancer. New Engl J Med 1977;296:1084–1088.

    Article  PubMed  CAS  Google Scholar 

  14. Goldberg RB, Bersohn I, Kew MC. Hypercholesterolaemia in primary cancer of the liver. S Afr Med J 1975;49:1464–1466.

    PubMed  CAS  Google Scholar 

  15. Steiner E, Velt P, Gutierrez O, Schwartz S, Chey W. Hepatocellular carcinoma presenting with intractable diarrhea. A radiologic-pathologic correlation. Arch Surg 1986;121:849–851.

    PubMed  CAS  Google Scholar 

  16. Gregory B, Ho VC. Cutaneous manifestations of gastrointestinal disorders. Part I [review]. J Am Acad Dermatol 1992; 26:153–166.

    Article  PubMed  CAS  Google Scholar 

  17. Stein CM, Gelfand M. Hepatocellular carcinoma presenting as a fever of undetermined origin. Cent Afr J Med 1985;31:21,22.

    PubMed  CAS  Google Scholar 

  18. Okada S. How to manage hepatic vein tumour thrombus in hepatocellular carcinoma [review]. J Gastroenterol Hepatol 2000;15:346–348.

    Article  PubMed  CAS  Google Scholar 

  19. Kew MC. Hepatocellular cancer. A century of progress [review]. Clin Liver Dis 2000;4:257–268.

    Article  PubMed  CAS  Google Scholar 

  20. Tatarinov YS. Presence of embryonal a-globulin in the serum of patients with primary hepatocellular carcinoma. Vopr Med Khim 1964;10:90.

    PubMed  CAS  Google Scholar 

  21. Alpert E. Human alpha1-fetoprotein (AFP): developmental biology and clinical significance [review]. Prog Liver Dis 1976;5:337–349.

    PubMed  CAS  Google Scholar 

  22. Carr BI, Flickinger JC, Lotze MT. Hepatobiliary cancers. In: Cancer: Principles and Practice of Oncology (DeVita VT, Hellman S, Rosenberg SA, eds.), Lippincott-Raven, Philadelphia, 1997, p. 1087.

    Google Scholar 

  23. Collier J, Sherman M. Screening for hepatocellular carcinoma [review]. Hepatology 1998;27:273–278.

    Article  PubMed  CAS  Google Scholar 

  24. Kew MC. a-fetoprotein in primary liver cancer and other diseases. Gut 1974;15:814.

    Article  PubMed  CAS  Google Scholar 

  25. 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;36:410–417.

    Article  PubMed  CAS  Google Scholar 

  26. Taketa K, Sekiya C, Namiki M, Akamatsu K, Ohta Y, Endo Y, Kosaka K. Lectin-reactive profiles of alpha-fetoprotein characterizing hepatocellular carcinoma and related conditions. Gastroenterology 1990;99:508–518.

    PubMed  CAS  Google Scholar 

  27. Sato Y, Nakata K, Kato Y, Shima M, Ishii N, Koji T, et al. Early recognition of hepatocellular carcinoma based on altered profiles of alpha-fetoprotein. New Engl J Med 1993;328:1802–1806.

    Article  PubMed  CAS  Google Scholar 

  28. Oka H, Saito A, Ito K, Kumada T, Satomura S, Kasugai H, et al. Multicenter prospective analysis of newly diagnosed hepatocellular carcinoma with respect to the percentage of lens culinaris agglutinin-reactive alpha-fetoprotein. J Gastroenterol Hepatol 2001;16:1378–1383.

    Article  PubMed  CAS  Google Scholar 

  29. Taketa K, Endo Y, Sekiya C, Tanikawa K, Koji T, Taga H, et al. A collaborative study for the evaluation of lectin-reactive alpha-fetoproteins in early detection of hepatocellular carcinoma. Cancer Res 1993;53:5419–5423.

    PubMed  CAS  Google Scholar 

  30. Liebman HA, Furie BC, Tong MJ, Blanchard RA, Lo KJ, Lee SD, et al. Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. New Engl J Med 1984;310:1427–1431.

    Article  PubMed  CAS  Google Scholar 

  31. Weitz IC, Liebman HA. Des-gamma-carboxy (abnormal) prothrombin and hepatocellular carcinoma: a critical review. Hepatology 1993;18:990–997.

    Article  PubMed  CAS  Google Scholar 

  32. Tanabe Y, Ohnishi K, Nomura F, Iida S. Plasma abnormal prothrombin levels in patients with small hepatocellular carcinoma. Am J Gastroenterol 1988;83:1386–1389.

    PubMed  CAS  Google Scholar 

  33. Marrero JA, Su GL, Wei W, Emick D, Conjeevaram HS, Fontana RJ, et al. Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from non-malignant liver disease in American patients. Hepatology 2003; 37:1114–1121.

    Article  PubMed  CAS  Google Scholar 

  34. Ishii M, Gama H, Chida N, Ueno Y, Shinzawa H, Takagi T, et al. Simultaneous measurements of serum alpha-fetoprotein and protein induced by vitamin K absence for detecting hepatocellular carcinoma. South Tohoku District Study Group. Am J Gastroenterol 2000; 95:1036–1040.

    PubMed  CAS  Google Scholar 

  35. Capurro M, Wanless IR, Sherman M, Deboer G, Shi W, Miyoshi E, et al. Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma. Gastroenterology 2003;125:89–97.

    Article  PubMed  CAS  Google Scholar 

  36. Kew MC, Wolf P, Whittaker D, Rowe P. Tumour-associated isoenzymes of gamma-glutamyl transferase in the serum of patients with hepatocellular carcinoma. Br J Cancer 1984;50:451–455.

    PubMed  CAS  Google Scholar 

  37. Tsai JF, Jeng JE, Chuang LY, Yang ML, Ho MS, Chang WY, et al. Clinical evaluation of urinary transforming growth factor-beta1 and serum alpha-fetoprotein as tumour markers of hepatocellular carcinoma. Br J Cancer 1997;75:1460–1466.

    PubMed  CAS  Google Scholar 

  38. Hamazaki K, Gochi A, Shimamura H, Kaihara A, Maruo Y, Doi Y, et al. Serum levels of circulating intercellular adhesion molecule 1 in hepatocellular carcinoma. Hepatogastroenterology 1996;43:229–234.

    PubMed  CAS  Google Scholar 

  39. Takahashi H, Saibara T, Iwamura S, Tomita A, Maeda T, Onishi S, et al. Serum alpha-L-fucosidase activity and tumor size in hepatocellular carcinoma. Hepatology 1994;19: 1414–1417.

    PubMed  CAS  Google Scholar 

  40. Tu DG, Wang ST, Chang TT, Chiu NT, Yao WJ. The value of serum tissue polypeptide specific antigen in the diagnosis of hepatocellular carcinoma. Cancer 1999;85:1039–1043.

    Article  PubMed  CAS  Google Scholar 

  41. Ishiguchi T, Shimamoto K, Fukatsu H, Yamakawa K, Ishigaki T. Radiologic diagnosis of hepatocellular carcinoma [review]. Semin Surg Oncol 1996;12:164–169.

    Article  PubMed  CAS  Google Scholar 

  42. Tanaka S, Kitamura T, Imaoka S, Sasaki Y, Taniguchi H, Ishiguro S. Hepatocellular carcinoma: sonographic and histologic correlation. Am J Roentgenol 1983;140:701–707.

    CAS  Google Scholar 

  43. Kudo M. Imaging diagnosis of hepatocellular carcinoma and premalignant/borderline lesions [review]. Semin Liver Dis 1999;19:297–309.

    PubMed  CAS  Google Scholar 

  44. Tanaka S, Kitamura T, Fujita M, Nakanishi K, Okuda S. Color Doppler flow imaging of liver tumors. Am J Roentgenol 1990;154:509–514.

    CAS  Google Scholar 

  45. Larcos G, Sorokopud H, Berry G, Farrell GC. Sonographic screening for hepatocellular carcinoma in patients with chronic hepatitis or cirrhosis: an evaluation. Am J Roentgenol 1998;171:433–435.

    CAS  Google Scholar 

  46. Dodd GD, Miller WJ, Baron RL, et al. Detection of malignant tumors in end-stage cirrhotic livers: efficacy of sonography as a screening technique. Am J Roentgenol 1992;159:727–733.

    Google Scholar 

  47. Pateron D, Ganne N, Trinchet JC, Aurousseau MH, Mal F, Meicler C, et al. Prospective study of screening for hepatocellular carcinoma in Caucasian patients with cirrhosis [comment]. J Hepatol 1994;20:65–71.

    Article  PubMed  CAS  Google Scholar 

  48. Choi BI. CT diagnosis of liver cancer. In: Liver Cancer (Okuda K, Tabor E, eds.), Churchill Livingstone, New York, 1997, p. 371.

    Google Scholar 

  49. Ros PR, Murphy BJ, Buck JL, Olmedilla G, Goodman Z. Encapsulated hepatocellular carcinoma: radiologic findings and pathologic correlation. Gastrointest Radiol 1990;15:233–237.

    Article  PubMed  CAS  Google Scholar 

  50. Oliver JH, Baron RL, Federle MP, Rockette HE Jr. Detecting hepatocellular carcinoma: value of unenhanced or arterial phase CT imaging or both used in conjunction with conventional portal venous phase contrast-enhanced CT imaging. Am J Roentgenol 1996;167:71–77.

    Google Scholar 

  51. Oliver JH, Baron RL, Carr BI. CT imaging of hepatocellular carcinoma: CT-arteriography versus triphasic helical contrast CT. Radiology 1997;205:144.

    Google Scholar 

  52. Miller WJ, Baron RL, Dodd GD, Federle MP. Malignancies in patients with cirrhosis: CT sensitivity and specificity in 200 consecutive transplant patients. Radiology 1994;193:645–650.

    PubMed  CAS  Google Scholar 

  53. Ngan H. Lipiodol computerized tomography: how sensitive and specific is the technique in the diagnosis of hepatocellular carcinoma? Br J Radiol 1990;63:771–775.

    Article  PubMed  CAS  Google Scholar 

  54. Ebara M. MRI diagnosis of hepatocellular carcinoma. In: Liver Cancer (Okuda K, Tabor E, eds.), Churchill Livingstone, New York, 1997, p. 361.

    Google Scholar 

  55. Lencioni R, Mascalchi M, Caramella D, Bartolozzi C. Small hepatocellular carcinoma: differentiation from adenomatous hyperplasia with color Doppler US and dynamic Gd-DTPAenhanced MR imaging. Abdominal Imaging 1996; 21:41–48.

    Article  PubMed  CAS  Google Scholar 

  56. Kew MC, Levin J. Scintigraphy in the diagnosis of hepatocellular carcinoma. In: Neoplasms of the Liver (Okuda K, Ishak KG, eds.), Springer-Verlag, Tokyo, 1987, p. 239.

    Google Scholar 

  57. Trojan J, Schroeder O, Raedle J, Baum RP, Herrmann G, Jacobi V, et al. Fluorine-18 FDG positron emission tomography for imaging of hepatocellular carcinoma. Am J Gastroenterol 1999;94:3314–3319.

    Article  PubMed  CAS  Google Scholar 

  58. Delbeke D, Martin WH, Sandler MP, Chapman WC, Wright JK Jr, Pinson CW. Evaluation of benign vs malignant hepatic lesions with positron emission tomography. Arch Surg 1998;133:510–515.

    Article  PubMed  CAS  Google Scholar 

  59. Schroder O, Trojan J, Zeuzem S, Baum RP. Limited value of fluorine-18-fluorodeoxyglucose PET for the differential diagnosis of focal liver lesions in patients with chronic hepatitis C virus infection. Nuklearmedizin 1998;37:279–285.

    PubMed  CAS  Google Scholar 

  60. Takayasu K. Hepatic angiography. In: Liver Cancer (Okuda K, Tabor E, eds.), Churchill Livingstone, New York, 1997, p. 347.

    Google Scholar 

  61. Ichikawa T, Federle MP, Grazioli L, Madariaga J, Nalesnik M, Marsh W. Fibrolamellar hepatocellular carcinoma: imaging and pathologic findings in 31 recent cases. Radiology 1999;213:352–361.

    PubMed  CAS  Google Scholar 

  62. Durand F, Regimbeau JM, Belghiti J, Sauvanet A, Vilgrain V, Terris B, et al. Assessment of the benefits and risks of percutaneous biopsy before surgical resection of hepatocellular carcinoma. J Hepatol 2001;35:254–258.

    Article  PubMed  CAS  Google Scholar 

  63. Kew MC. The detection and treatment of small hepatocellular carcinoma. In: Viral Hepatitis and Liver Disease (Hollinger FB, Lemon SM, Margolis H, eds.), Williams and Wilkins, Baltimore, 1991, p. 515.

    Google Scholar 

  64. Colombo M, de Franchis R, Del Ninno E, Sangiovanni A, De Fazio C, Tommasini M, et al. Hepatocellular carcinoma in Italian patients with cirrhosis. New Engl J Med 1991;325: 675–680.

    Article  PubMed  CAS  Google Scholar 

  65. 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;2:1129–1133.

    Article  PubMed  CAS  Google Scholar 

  66. Fargion S, Fracanzani AL, Piperno A, Braga M, D’Alba R, Ronchi G, et al. Prognostic factors for hepatocellular carcinoma in genetic hemochromatosis. Hepatology 1994;20:1426–1431.

    Article  PubMed  CAS  Google Scholar 

  67. Park SZ, Nagorney DM, Czaja AJ. Hepatocellular carcinoma in autoimmune hepatitis. Dig Dis Sci 2000;45:1944–1948.

    Article  PubMed  CAS  Google Scholar 

  68. Caballeria L, Pares A, Castells A, Gines A, Bru C, Rodes J. Hepatocellular carcinoma in primary biliary cirrhosis: similar incidence to that in hepatitis C virus-related cirrhosis. Am J Gastroenterol 2001;96:1160–1163.

    PubMed  CAS  Google Scholar 

  69. Shibuya A, Tanaka K, Miyakawa H, Shibata M, Takatori M, Sekiyama K, et al. Hepatocellular carcinoma and survival in patients with primary biliary cirrhosis. Hepatology 2002;35: 1172–1178.

    Article  PubMed  Google Scholar 

  70. Bugianesi E, Leone N, Vanni E, Marchesini G, Brunello F, Carucci P, et al. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 2002;123:134–140.

    Article  PubMed  Google Scholar 

  71. Marrero JA, Fontana RJ, Su GL, Conjeevaram HS, Emick DM, Lok AS. NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States. Hepatology 2002;36:1349–1354.

    PubMed  Google Scholar 

  72. Sheu J, Sung J, Chen D, Yang PM, Lai MY, Lee CS, et al. Growth rate of asymptomatic hepatocellular carcinoma and its clinical implications. Gastroenterology 1985;89:259–266.

    PubMed  CAS  Google Scholar 

  73. Seeff LB, Hoofnagle JH. National Institutes of Health Consensus Development Statement on the management of hepatitis C. Hepatology 2002;36:S3–S20.

    Article  Google Scholar 

  74. Lok ASF, McMahon BJ. Chronic hepatitis B. Hepatology 2001;34:1225–1241.

    Article  PubMed  CAS  Google Scholar 

  75. UNOS Policies and Bylaws. Organ distribution: allocation of livers. Policy 3.6.4.4. Liver Transplant Candidates with Hepatocellular Carcinoma. Last revised 2/14/03.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Hepatology, and Nutrition, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA

    David A. Sass MD

  2. Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA

    Kapil B. Chopra MD, DM, FACP

Authors
  1. David A. Sass MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kapil B. Chopra MD, DM, FACP
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Liver Cancer Center, Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA

    Brian I. Carr MD, FRCP, PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Sass, D.A., Chopra, K.B. (2005). Clinical Features and Diagnostic Evaluation of Hepatocellular Carcinoma. In: Carr, B.I. (eds) Hepatocellular Cancer. Current Clinical Oncology. Humana Press. https://doi.org/10.1007/978-1-59259-844-1_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-844-1_3

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-125-7

  • Online ISBN: 978-1-59259-844-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation