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
• Most common primary liver malignancy in adults
• Highest incidence in Southeast Asia and Africa ^[1]
• Peak incidence in the US: 70–75 years
• Peak incidence in Africa and Asia: 30–40 years
• ♂ > ♀

Epidemiological data refers to the US, unless otherwise specified.

• Liver cirrhosis: 80% of cases (see “Etiology” in cirrhosis) ^[2]
• Risk factors independent of cirrhosis
  • Chronic hepatitis B or C virus infection
  • Alcoholic liver disease
  • Nonalcoholic steatohepatitis (NASH)
  • Hemochromatosis
  • Wilson's disease
  • Alpha-1 antitrypsin deficiency
  • Hepatic autoimmune diseases (e.g., autoimmune hepatitis)
  • Schistosomiasis
  • Glycogen storage disease
  • Chronic ingestion of food contaminated with aflatoxin (carcinogen produced by Aspergillus flavus)
    • 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!

• Usually asymptomatic apart from symptoms of the underlying disease (mostly cirrhosis or hepatitis)
• Possible symptoms of advanced disease
  • Weight loss, anorexia
  • Hepatomegaly and right upper quadrant tenderness
  • Jaundice
  • Ascites

Laboratory tests

• ↑ Serum alpha-fetoprotein (AFP)
• Laboratory studies consistent with hepatitis and cirrhosis (e.g., ↑ transaminases, 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

• Ultrasound: best initial 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 or MRI (with contrast): confirmatory test
  • Hypodense lesions (single or multifocal)
  • Irregular mass borders
  • Possible local invasion
• 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

Malignant liver tumors

• Metastatic liver disease
  • Epidemiology
    • Most common malignant lesion of the liver
    • Typical primary tumor site: gastrointestinal tract (colon, stomach, pancreas), lungs, and breasts
  • Diagnostics
    • Abnormal liver function tests
    • Ultrasound
    • CT scan: typically multiple hypodense lesions (solitary metastases are very rare)
      • Alternative: MRI
• Intrahepatic cholangiocellular carcinoma (CCC): second most common primary hepatic malignancy after HCC ^[3]
• Hepatic angiosarcoma ^[4]
  • Epidemiology: third most common primary hepatic malignancy
  • Etiology: associated with exposure to vinyl chloride, arsenic, and thorium dioxide
  • Histology (biopsy): endothelial cells positive for PECAM-1 (CD31)
  • Treatment: surgical resection +/- adjuvant therapy ^[5]
  • Prognosis: high rate of recurrence, poor overall prognosis
• 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

The differential diagnoses listed here are not exhaustive.