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Incidence (worldwide): 841,080 cases per year Stage at Presentation
  13.9 cases per 100,000 men Stage A: 35%
  4.9 cases per 100,000 women Stage B: 25%
Deaths (worldwide): 781,631 per year, 5-year OS 18% Stage C: 10%
Median age: 50–60 years Stage D: 30%
Male to female ratio: 3.7: 2.5


History and clinical examination

  • Risk factors for chronic liver disease: intravenous drug abuse, alcohol intake, metabolic syndrome (obesity, diabetes, arterial hypertension)

  • Symptoms and signs of chronic liver disease: jaundice, ascites, encephalopathy, bleeding, splenomegaly

  • Performance status and nutritional state


Laboratory analysis

  • Etiology of liver disease: HBV (HBsAg, anti-HBc), HCV (anti-HCV), iron status, autoimmune disease, liver function: prothrombin time, albumin, bilirubin

  • Complete blood cell count including platelets

  • Tumor marker: serum alpha fetoprotein (AFP)


Assessment of portal hypertension

  • Upper endoscopy: varices and/or hypertensive gastropathy

Imaging studies

  • Liver dynamic (multiple phase) MRI or CT for diagnosis and evaluation of tumor extent; number and size of nodules, vascular invasion, extrahepatic spread

  • CT of the chest, abdomen, and pelvis to rule out extrahepatic spread

  • Imaging performed, interpreted, and reported through the CT MRI Liver Imaging Reporting and Data System (CT/MRI LI-RADS)—an imaging-based diagnostic system used in patients at high risk of hepatocellular carcinoma (HCC). It assigns each liver abnormality a category that reflects the probability of the finding representing a benign cause, HCC, or other malignancy (see below)


Tumor biopsy

  • Nodules with non-diagnostic imaging

  • Required to diagnose HCC in non-cirrhotic liver


Vogel A et al. Ann Oncol 2018;29(Suppl 4):iv238–iv255


Diagnostic Criteria for HCC: CT/MRI LI-RADS

  • Diagnosis of HCC can be established based on imaging (without biopsy confirmation) in patients who have cirrhosis

  • Criteria on multiphase imaging to enable noninvasive diagnosis of HCC: nodule ≥1 cm, arterial phase hyperenhancement, and depending on size, a combination of washout in the venous or delayed phase, threshold growth, and capsule appearance

  • If criteria not met, liver biopsy should be considered

  • AFP and other serum biomarkers have a minor role in the diagnosis of HCC

  • At-risk patients with abnormal surveillance results or a clinical suspicion of HCC should undergo multiphase CT or MRI for diagnostic testing

  • LI-RADS system designates lesions to category codes according to the probability of being benign, HCC, or other hepatic malignant neoplasm (cholangiocarcinoma or combined) (Figure 1)

  • The probability of HCC associated with each LI-RADS category guides management

  • LI-RADS 1 and LI-RADS 2:

    • − Definitely benign (cysts and typical hemangiomas) and probably benign (atypical hemangiomas and focal parenchymal abnormalities) lesions, respectively

    • − LI-RADS 1 lesions have an average probability of HCC of 0%

    • − LI-RADS 2 lesions have an average probability of HCC of 11%

  • LI-RADS 3:

    • − Low probability of HCC (vascular pseudo-lesions and small HCCs, distinctive solid nodule with only some imaging features consistent with HCC diagnosis)

    • − Average probability of HCC of 33%

    • − Followed prospectively, ...

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