eMedicine Specialties > Radiology > Gastrointestinal

Hepatocellular Carcinoma

Author: Daniel R Jacobson, MD, MS, Clinical Instructor, Department of Radiology, University of Rochester School of Medicine, Radiology Residency Program Director, Rochester General Hospital
Contributor Information and Disclosures

Updated: Feb 20, 2009

Introduction

Background

Hepatocellular carcinoma (HCC) is the most common primary hepatic tumor and one of the most common cancers worldwide. HCC is a primary malignancy of hepatocellular origin.1

CT scan in the hepatic arterial phase of contrast...

CT scan in the hepatic arterial phase of contrast enhancement showing neovascularity in a low-density hepatic mass.

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CT scan in the hepatic arterial phase of contrast...

CT scan in the hepatic arterial phase of contrast enhancement showing neovascularity in a low-density hepatic mass.


Ultrasound shows hyperechoic mass representing he...

Ultrasound shows hyperechoic mass representing hepatocellular carcinoma.

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Ultrasound shows hyperechoic mass representing he...

Ultrasound shows hyperechoic mass representing hepatocellular carcinoma.


For excellent patient education resources, visit eMedicine's Liver, Gallbladder, and Pancreas Center and Hepatitis Center. Also, see eMedicine's patient education article Cirrhosis.
 

Related eMedicine topics:

 Hepatocellular Carcinoma (from General Surgery)

Hepatocellular Carcinoma (from Pediatrics: General Medicine)

Hepatocellular Carcinoma, Fibrolamellar

Liver Tumors

Liver, Metastases

Pathophysiology

Hepatocellular carcinoma (HCC) is a malignant tumor of hepatocellular origin that develops in patients with risk factors such as alcohol abuse, viral hepatitis, and metabolic liver disease. It can also occur, rarely, in patients with normal liver parenchyma.2  

Grossly, HCC can undergo hemorrhage and necrosis because of a lack of fibrous stroma. Vascular invasion, particularly of the portal system, is common. Invasion of the biliary system is less common. Aggressive HCC can cause hepatic rupture and hemoperitoneum.

There are 3 growth patterns exhibited by HCC:  

  • Solitary mass - Often large
  • Multifocal or nodular pattern - Multiple nodules
  • Diffuse - Multiple, small foci scattered diffusely throughout the liver

Microscopically, HCC cells resemble normal hepatocytes and can be confused with cells of hepatic adenoma. Tumors that are more differentiated can produce bile.

HCC can produce alpha-fetoprotein (AFP) as well as other serum proteins.

Frequency

United States

Hepatocellular carcinoma (HCC) is rare in the Western Hemisphere. The prevalence is 4 cases per 100,000 population, or 2% of all malignancies. Approximately 5,000-10,000 cases per year are seen. Prevalence rates in the United States vary among ethnic groups, with the highest rate being in men of Chinese descent. In the United States, the most common causes of HCC are alcoholic cirrhosis, steroid use, and hemochromatosis.

International

Hepatocellular carcinoma (HCC) is more common in Asia and Africa than in the United States. The highest incidence of HCC is in Japan (4-5%). Other high-incidence regions include sub-Saharan Africa. Internationally, the common causes of HCC are hepatitis B, hepatitis C, and aflatoxin exposure.

Mortality/Morbidity

  • Most patients with hepatocellular carcinoma (HCC) die within 1 year after diagnosis. Survival is dependent on tumor size and on associated diseases at the time of diagnosis. Patients with cirrhosis have a shorter survival. Surgical cure is possible in less than 5% of patients.
  • The causes of death include bleeding (variceal, intraperitoneal) and cachexia.

Race

  • A high incidence is seen in Japan and Africa.
  • In the United States, hepatocellular carcinoma (HCC) is most common in men of Chinese descent, probably because of the high incidence of viral hepatitis in this subgroup.

Sex

  • In high-incidence regions of the world (ie, Asia, Africa), the male-to-female ratio is approximately 8:1.
  • In low-incidence regions (ie, Western Hemisphere), the male-to-female ratio is approximately 2:1.

Age

  • In high-incidence regions of the world (ie, Asia, Africa), patients present at age 30-50 years.
  • In low-incidence regions (ie, Western Hemisphere), patients present at age 70-80 years. Patients with cirrhosis may present earlier.

Presentation

Clinical presentations vary among high-incidence and low-incidence regions.

In high-incidence regions (ie, Asia, Africa), the clinical presentation of hepatocellular carcinoma (HCC) tends to be aggressive and includes bleeding, hepatic rupture, and hemoperitoneum.

In low-incidence regions (ie, Western Hemisphere), the clinical presentation of HCC tends to be less aggressive and includes symptoms such as fever of unknown origin, abdominal pain, malaise, weight loss, and hepatomegaly. Jaundice is rare.

Liver function tests can be normal. Alpha-fetoprotein (AFP) levels may be elevated because this protein is commonly produced by HCC; however, this is an insensitive parameter because AFP levels may be normal in more than one third of patients.

Other proteins can be produced by HCC and cause paraneoplastic syndromes, such as erythrocytosis, hypercalcemia, hypoglycemia, and hirsutism.3

Preferred Examination

Cross-sectional imaging with computed tomography (CT) and magnetic resonance imaging (MRI) is most commonly used to detect hepatocellular carcinoma (HCC). CT is frequently the first examination; however, MRI has superior contrast resolution and may better detect lesions less than 1 cm in diameter.

Ultrasound (US) can be sensitive in detecting HCC and, depending on the operator, can detect small lesions. US can evaluate for vascular invasion of the portal and hepatic veins through color Doppler imaging.

Nuclear medicine imaging, angiography, and plain films are less useful.

Limitations of Techniques

Plain films are nonspecific but may show a mass in the upper abdomen if the hepatocellular carcinoma (HCC) is large.

Nuclear medicine provides relatively nonspecific findings. The HCC may present as a "cold" defect on a sulfur-colloid study or may demonstrate uptake of radiopharmaceuticals if the mass produces bile. Gallium uptake is seen in 90% of HCCs.

The US appearance of HCC varies; it may be hyperechoic or hypoechoic. A small hyperechoic HCC may be confused with hemangioma.

Perform CT in hepatic arterial, portal venous, and delayed phases. Similarly, if MRI is used, precontrast, arterial, venous, and delayed phases are essential. Enhancement patterns of regenerative, dysplastic, and HCC nodules overlap; therefore, nodules of cirrhosis may not be differentiated from small HCCs.

Angiography study may show increased vascularity of other hepatic tumors, including benign masses.

Differential Diagnoses

Cholangiocarcinoma
Hepatocellular Carcinoma, Fibrolamellar
Focal Nodular Hyperplasia
Liver, Metastases
Hepatic Adenoma
Hepatic Carcinoma, Primary
Hepatoblastoma

Other Problems to Be Considered

Metastatic disease
Angiosarcoma
Regenerative nodules
Dysplastic nodules
Hemangioma

More on Hepatocellular Carcinoma

Overview: Hepatocellular Carcinoma
Imaging: Hepatocellular Carcinoma
Follow-up: Hepatocellular Carcinoma
Multimedia: Hepatocellular Carcinoma
References
Further Reading
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References

  1. Yau T, Chan P, Epstein R, Poon RT. Management of advanced hepatocellular carcinoma in the era of targeted therapy. Liver Int. Jan 2009;29(1):10-7. [Medline].

  2. Yang Y, Nagano H, Ota H, et al. Patterns and clinicopathologic features of extrahepatic recurrence of hepatocellular carcinoma after curative resection. Surgery. Feb 2007;141(2):196-202. [Medline].

  3. Dorfman JD, Schulick R, Choti MA, et al. Differences in characteristics of patients with and without known risk factors for hepatocellular carcinoma in the United States. World J Gastroenterol. Feb 7 2007;13(5):781-4. [Medline].

  4. Ma Y, Zhang XL, Li XY, Zhang L, Su HH, Zhan CY. [Value of computed tomography and magnetic resonance imaging in diagnosis and differential diagnosis of small hepatocellular carcinoma.]. Nan Fang Yi Ke Da Xue Xue Bao. Dec 2008;28(12):2235-8. [Medline].

  5. Peterson MS, Baron RL, Marsh JW Jr, et al. Pretransplantation surveillance for possible hepatocellular carcinoma in patients with cirrhosis: epidemiology and CT-based tumor detection rate in 430 cases with surgical pathologic correlation. Radiology. Dec 2000;217(3):743-9. [Medline].

  6. Minami Y, Kudo M, Chung H, et al. Contrast harmonic sonography-guided radiofrequency ablation therapy versus B-mode sonography in hepatocellular carcinoma: prospective randomized controlled trial. AJR Am J Roentgenol. Feb 2007;188(2):489-94. [Medline].

  7. Torzilli G, Palmisano A, Del Fabbro D, et al. Contrast-enhanced intraoperative ultrasonography during surgery for hepatocellular carcinoma in liver cirrhosis: is it useful or useless? A prospective cohort study of our experience. Ann Surg Oncol. Apr 2007;14(4):1347-55. [Medline].

  8. Gheorghe L, Iacob S, Gheorghe C. Real-time sonoelastography - a new application in the field of liver disease. J Gastrointestin Liver Dis. Dec 2008;17(4):469-74. [Medline].

  9. Maluf DG, Stravitz RT, Williams B, et al. Multimodality therapy and liver transplantation in patients with cirrhosis and hepatocellular carcinoma: 6 years, single-center experience. Transplant Proc. Jan-Feb 2007;39(1):153-9. [Medline].

  10. Zhang FJ, Li CX, Jiao DC, Zhang NH, Wu PH, Duan GF, et al. CT guided 125iodine seed implantation for portal vein tumor thrombus in primary hepatocellular carcinoma. Chin Med J (Engl). Dec 5 2008;121(23):2410-4. [Medline].

  11. Morris-Stiff G, Gomez D, de Liguori Carino N, Prasad KR. Surgical management of hepatocellular carcinoma: Is the jury still out?. Surg Oncol. Dec 3 2008;[Medline].

  12. Baron RL, Oliver JH 3rd, Dodd GD 3rd. Hepatocellular carcinoma: evaluation with biphasic, contrast-enhanced, helical CT. Radiology. May 1996;199(2):505-11. [Medline].

  13. Bartolozzi C, Donati F, Cioni D. MnDPDP-enhanced MRI vs dual-phase spiral CT in the detection of hepatocellular carcinoma in cirrhosis. Eur Radiol. 2000;10(11):1697-702. [Medline].

  14. Casillas VJ, Amendola MA, Gascue A. Imaging of nontraumatic hemorrhagic hepatic lesions. Radiographics. Mar-Apr 2000;20(2):367-78. [Medline].

  15. Chalasani N, Horlander JC, Said A. Screening for hepatocellular carcinoma in patients with advanced cirrhosis. Am J Gastroenterol. Oct 1999;94(10):2988-93. [Medline].

  16. Chen JH, Chai JW, Huang CL. Proximal arterioportal shunting associated with hepatocellular carcinoma: features revealed by dynamic helical CT. AJR Am J Roentgenol. Feb 1999;172(2):403-7. [Medline].

  17. Fernandez MP, Redvanly RD. Primary hepatic malignant neoplasms. Radiol Clin North Am. Mar 1998;36(2):333-48. [Medline].

  18. Fukuda H, Takahashi J, Fujiwara T. High accumulation of 2-deoxy-2-fluorine-18-fluoro-D-galactose by well- differentiated hepatomas of mice and rats. J Nucl Med. May 1993;34(5):780-6. [Medline].

  19. Gazelle GS, Goldberg SN, Solbiati L, Livraghi T. Tumor ablation with radio-frequency energy. Radiology. Dec 2000;217(3):633-46. [Medline].

  20. Gore RM, Levine MS. Textbook of Gastrointestinal Radiology. Philadelphia, Pa: WB Saunders Co; 2000.

  21. Ito K, Honjo K, Fujita T. Liver neoplasms: diagnostic pitfalls in cross-sectional imaging. Radiographics. Mar 1996;16(2):273-93. [Medline].

  22. Ito K, Mitchell DG, Honjo K. Biphasic contrast-enhanced multisection dynamic MR imaging of the liver: potential pitfalls. Radiographics. May-Jun 1997;17(3):693-705. [Medline].

  23. Kelekis NL, Semelka RC, Worawattanakul S, de Lange EE, Ascher SM, Ahn IO. Hepatocellular carcinoma in North America: a multi-institutional study of appearance on T1-weighted, T2-weighted, and serial gadolinium-enhanced gradient-echo images. AJR Am J Roentgenol. Apr 1998;170(4):1005-13. [Medline].

  24. Larcos G, Sorokopud H, Berry G. Sonographic screening for hepatocellular carcinoma in patients with chronic hepatitis or cirrhosis: an evaluation. AJR Am J Roentgenol. Aug 1998;171(2):433-5. [Medline].

  25. Lin EC, Kuni CC. Radionuclide imaging of hepatic and biliary disease. Semin Liver Dis. May 2001;21(2):179-94. [Medline].

  26. Livraghi T, Goldberg SN, Lazzaroni S. Hepatocellular carcinoma: radio-frequency ablation of medium and large lesions. Radiology. Mar 2000;214(3):761-8. [Medline].

  27. Mergo PJ, Ros PR, Buetow PC. Diffuse disease of the liver: radiologic-pathologic correlation. Radiographics. Nov 1994;14(6):1291-307. [Medline].

  28. Oliver JH 3rd, Baron RL, Federle MP. 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. AJR Am J Roentgenol. Jul 1996;167(1):71-7. [Medline].

  29. Powers C, Ros PR, Stoupis C. Primary liver neoplasms: MR imaging with pathologic correlation. Radiographics. May 1994;14(3):459-82. [Medline].

  30. Rossi S, Buscarini E, Garbagnati F. Percutaneous treatment of small hepatic tumors by an expandable RF needle electrode. AJR Am J Roentgenol. Apr 1998;170(4):1015-22. [Medline].

  31. Sironi S, Livraghi T, Meloni F. Small hepatocellular carcinoma treated with percutaneous RF ablation: MR imaging follow-up. AJR Am J Roentgenol. Nov 1999;173(5):1225-9. [Medline].

  32. Tang Y, Yamashita Y, Arakawa A. Detection of hepatocellular carcinoma arising in cirrhotic livers: comparison of gadolinium- and ferumoxides-enhanced MR imaging. AJR Am J Roentgenol. Jun 1999;172(6):1547-54. [Medline].

  33. Yamamoto H, Yamashita Y, Yoshimatsu S. Hepatocellular carcinoma in cirrhotic livers: detection with unenhanced and iron oxide-enhanced MR imaging. Radiology. Apr 1995;195(1):106-12. [Medline].

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Keywords

hepatocellular carcinoma, hepatoma, typical hepatocellular carcinoma, primary liver carcinoma, clear cell carcinoma of the liver, HCC

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Contributor Information and Disclosures

Author

Daniel R Jacobson, MD, MS, Clinical Instructor, Department of Radiology, University of Rochester School of Medicine, Radiology Residency Program Director, Rochester General Hospital
Daniel R Jacobson, MD, MS is a member of the following medical societies: American College of Radiology, American Roentgen Ray Society, Association of University Radiologists, and Radiological Society of North America
Disclosure: Nothing to disclose.

Medical Editor

John L Haddad, MD, Clinical Associate Professor, Department of Radiology, Weill Medical College of Cornell University; Director of Body MRI, Department of Radiology, Methodist Hospital in Houston
John L Haddad, MD is a member of the following medical societies: American College of Radiology, American Medical Association, and Radiological Society of North America
Disclosure: Nothing to disclose.

Pharmacy Editor

Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.

Managing Editor

Udo P Schmiedl, MD, PhD, Clinical Professor, Department of Radiology, University of Washington; Consulting Staff, Swedish Medical Center, University of Washington Medical Center, Seattle Radiologists
Udo P Schmiedl, MD, PhD is a member of the following medical societies: American College of Radiology and Radiological Society of North America
Disclosure: Nothing to disclose.

CME Editor

Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute
Robert M Krasny, MD is a member of the following medical societies: American Roentgen Ray Society and Radiological Society of North America
Disclosure: Nothing to disclose.

Chief Editor

John Karani, MBBS, FRCR, Consulting Staff, Department of Radiology, King's College Hospital, London
Disclosure: Nothing to disclose.

 
 
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