Hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a malignant, most often solitary tumor of the liver, which occurs primarily in patients with preexisting liver cirrhosis or chronic hepatitis. Typically, it is an incidental diagnosis in these high-risk patients that is made either via ultrasound or an increase in the hepatic tumor marker alpha-fetoprotein. Most patients typically present with symptoms caused by underlying disease (e.g., ascites, jaundice) rather than the tumor itself. Potentially curative treatment options include tumor resection, liver transplantation, and ablative therapies. Unfortunately, it is usually not possible to remove all tumor tissue, which explains the poor prognosis of HCC. In western countries, the five-year survival is less than 50%.

• Fifth most common malignancy worldwide
• Highest incidence in Southeast Asia and Africa
• Peak incidence in the US: 70–75 years
• Peak incidence in Africa and Asia: 30–40 years
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References:^[1]

Epidemiological data refers to the US, unless otherwise specified.

• Liver cirrhosis (80% of cases)
• Risk factors independent of cirrhosis
  • Chronic hepatitis B or C virus infection
  • Nonalcoholic steatohepatitis (NASH)
  • Hemochromatosis
  • Wilson's disease
  • Alpha-1 antitrypsin deficiency
  • Schistosomiasis
  • Glycogen storage disease
  • Chronic ingestion of food contaminated with aflatoxin → results in chronic aflatoxicosis
    • Results in G:C → T:A transversion in codon 249 of TP53 gene leading to an inactivating mutation

Aflatoxins are considered one of the most potent carcinogens!

References:^[2][3]

• Usually asymptomatic apart from symptoms of the underlying disease (mostly cirrhosis or hepatitis)
• Metastasis is uncommon and usually only occurs in advanced stages
• Possible symptoms in advanced disease
  • Weight loss, cachexia
  • Hepatomegaly and right upper quadrant tenderness
  • Ascites and jaundice

References:^[3][4]

Laboratory tests

• ↑ Serum alpha-fetoprotein (AFP)
• Laboratory studies consistent with hepatitis and cirrhosis (e.g., ↑ LFTs, positive hepatitis serologies, ↓ coagulation factors)
• Paraneoplastic syndromes: erythrocytosis , hypoglycemia, hypercalcemia

In patients with cirrhosis of the liver or chronic hepatitis B/C infection, AFP is used as a screening test for HCC!

Imaging

Contrast-enhanced studies using ultrasound, MRI, or CT are most useful in the evaluation of a liver mass

• Ultrasound: first test
  • Irregular mass borders
  • Echogenicity ranging from homogeneous to inhomogeneous and from hypoechoic to hyperechoic
  • Vascular invasion of the tumor may be visible (e.g., portal vein thrombosis)
  • Underlying cirrhosis may be seen
• Abdominal CT (confirmatory test): typically shows a single hypodense lesion with irregular borders and possible local invasion
  • Alternative: MRI
• Chest CT: detection of pulmonary metastases (rare)
• Bone scintigraphy: detection of bone metastases (rare)

Liver biopsy

• Can provide a definitive diagnosis but carries the risk of bleeding and tumor spread
• Recommended when both lab and imaging studies are inconclusive

References:^[3][4]

Malignant liver tumors

• Metastatic liver disease
  • Epidemiology
    • Most common malignant lesion of the liver
    • Primary tumor site: gastrointestinal tract (colon, stomach, pancreas), lungs, and breasts
  • Diagnostics
    • Abnormal liver function tests
    • Ultrasound
    • CT scan: typically multiple hypodense lesions
      • Alternative: MRI
• Intrahepatic cholangiocellular carcinoma (CCC): second most common primary hepatic malignancy after HCC
• Hepatic angiosarcoma
  • Epidemiology
    • Third most common primary hepatic malignancy
    • High rate of recurrence
    • Poor prognosis
  • Etiology: associated with exposure to vinyl chloride, arsenic, and thorium dioxide
  • Resistant to treatment (chemotherapy and radiotherapy)
  • Biopsy showing endothelial cells positive for PECAM-1 (CD31)
• Primary hepatic lymphoma

Benign liver tumors

• Hepatic cyst
• Liver hemangioma
• Focal nodular hyperplasia (FNH)
• Hepatocellular adenoma with/without dysplasia
• Arteriovenous malformation
• Hepatic lipoma
• Regenerative liver nodules in cases of cirrhosis

References:^[5][6][7]

The differential diagnoses listed here are not exhaustive.

• Curative therapeutic options: potentially for patients with retained liver function
  • Surgical resection
  • Liver transplantation
  • Ablative therapies (mostly palliative, but can also be curative) result in shrinking and scarring of the tumor
    • Radiofrequency ablation (RFA): A catheter is placed within the tumor to induce heat necrosis via pulsed release of high-frequency waves.
    • Transcatheter arterial chemoembolization (TACE): local application of chemotherapy and embolic agent
    • Percutaneous ethanol injection (PEI)
    • Selective internal radiation therapy (SIRT)
• Follow-up:
  • Vaccination against HBV in high-risk individuals
  • Surveillance with ultrasound in patients with cirrhosis or chronic hepatitis B
• Palliative care: primarily for decompensated disease, unresectable, multinodular disease, or metastatic disease

#References:^[8]