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Hepatocellular carcinoma
Other Resources UpToDate PubMed

Hepatocellular carcinoma

Contributors: Beatriz Malibiran, Jennifer J. Findeis-Hosey MD
Other Resources UpToDate PubMed


Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver in adults over the age of 65 years worldwide and is considered the third leading cause of cancer death. In the United States, the ratio of incidence of HCC between men and women is 2.5 to 1. The incidence and sex ratio of HCC varies regionally, and the majority of cases are diagnosed in developing nations. The incidence of HCC is highest in East Asia, Southeast Asia, and sub-Saharan Africa where disease is most commonly associated with chronic viral hepatitis B or C infection. Major risk factors for developing HCC include cirrhosis, chronic viral hepatitis, dietary aflatoxin, diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD) (nonalcoholic fatty liver disease [NAFLD]), and alcohol abuse. Children are rarely affected; the only known risk factor in this population is chronic hepatitis B carrier status. In the United States, data suggests that the incidence of HCC may have remained stable since 2013, which may be attributed to improvements in antiviral therapy.

Patients are typically asymptomatic in the early stages of the disease. In the United States, right upper quadrant abdominal pain, weight loss, and malaise are common presenting symptoms. Jaundice, ascites, and hepatosplenomegaly may occur in patients with bile duct obstruction. Late findings include portal hypertension, abdominal bleeding, encephalopathy, and liver failure.

The Barcelona Clinic Liver Cancer algorithm is widely used for HCC staging:
  • Very early stage (0): Solitary nodules ≤ 2 cm. Treatment includes ablation or resection.
  • Early stage (A): Solitary nodule > 2 cm OR 2-3 nodules all ≤ 3 cm. Treatment options include resection, transplantation, or ablation.
  • Intermediate stage (B): > 3 nodules OR ≥ 2 nodules if any are > 3 cm. Treat with chemo-embolization.
  • Advanced stage (C): Macrovascular invasion OR extrahepatic spread. Treat with systemic therapies.
  • Terminal stage (D): End-stage liver function. Nontransplantable HCC. Supportive care.


C22.0 – Liver cell carcinoma

25370001 – Hepatocellular carcinoma

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Diagnostic Pearls

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Differential Diagnosis & Pitfalls

  • Hepatic adenoma – A benign lesion, generally uncommon but more common among women than men. Risk factors include long-term oral contraceptive use and estrogen exposure during pregnancy. Up to 30% of cases are complicated by bleeding.
  • Dysplastic nodules from Liver cirrhosis
  • Fibrous nodular hyperplasia
  • Cholangiocarcinoma
  • Pyogenic liver abscess
  • Metastatic cancer (Colon cancer / Rectal carcinoma, Pancreatic carcinoma, Gastric cancer) – distinguish with radiology and biopsy histology

Best Tests

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Management Pearls

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Drug Reaction Data

Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.

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Last Reviewed:04/26/2018
Last Updated:07/31/2023
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Hepatocellular carcinoma
A medical illustration showing key findings of Hepatocellular carcinoma : Jaundice, Ascites, Hypoalbuminemia, Hyperbilirubinemia, Splenomegaly, PT prolonged, PLT decreased
Imaging Studies image of Hepatocellular carcinoma - imageId=8358911. Click to open in gallery.  caption: '<span>Grayscale ultrasound image of the liver demonstrating a heterogeneously hyperechoic mass in the right lobe of the liver. Pathology proven hepatocellular carcinoma.</span>'
Grayscale ultrasound image of the liver demonstrating a heterogeneously hyperechoic mass in the right lobe of the liver. Pathology proven hepatocellular carcinoma.
Copyright © 2024 VisualDx®. All rights reserved.