Incidence and Risk Factors

Cancer of the liver is a rare malignancy in the United States, but in parts of Asia and Africa, it is one of the most common malignancies. In the United States, the average age on onset is 60 to 70 years; the disease occurs more frequently in males than females.

There is a strong association between chronic hepatitis B infection and the development of heptaocellular carcinoma. People with cirrhosis also have an increased risk of liver cancer. Other possible hepatocarcinogens include aflatoxin, nitrosamines, oral estrogen compounds, and numerous other chemicals.

Clinical Manifestations and Diagnosis

Signs of liver cancer include weakness, anorexia, fever of unknown origin, abdominal fullness or bloating, and dull upper quadrant abdominal pain. The clinical presentation will vary depending on the presence or absence of cirrhosis. Patients with cirrhosis exhibit rapid onset of symptoms; in the absence of cirrhosis, signs are much more subtle. As the tumor grows, pain may radiate to the back. Patients must be assessed carefully, as weight loss is often obscured by ascites. The liver is generally tender to palpation, and jaundice and portal hypertension may be present.

Diagnosis is made using radioisotope scans, CT scans, or hepatic arteriography. Many patients will have advanced disease at diagnosis. Cancer of the liver spreads throughout the organ and invades the portal vein and lymphatics. The most common sites of distant metastases are the lungs and brain.

Treatment

Surgical resection is attempted if no nodal involvement or distant spread is found. Even with resection, recurrence of liver cancer is common, and 5-year survival is rare. Patients may be treated with chemotherapy infused directly into the hepatic circulation. With this type of treatment (intra-arterial chemotherapy), a catheter is surgically placed in the hepatic artery and the chemotherapeutic agent is continuously infused. The most commonly used agents are 5-FU, doxorubicin, and methotrexate. Side effects of this technique include toxic hepatitis (which subsides after discontinuation of therapy) and catheter displacement or occlusion.

Radioimmunotherapy is an experimental form of treatment used for some types of liver cancer. A radioactive isotope is attached to a radiolabeled antibody against ferritin, a specific protein found in human liver tumors. The isotope is given intravenously and concentrates in the liver, where it radiates the tumor internally. No immediate treatment side effects have been noted, but thrombocytopenia and neutropenia occur 4-6 weeks after treatment.

The prognosis for liver carcinoma patients is poor. Untreated patients usually die in 3-4 months; treated patients may live 6 to 18 months if they respond to therapy. Long-term survival is seen occasionally after successful subtotal hepatectomy for noninvasive carcinoma. Because the normal metabolic and storage functions of the liver are impaired, patients are at risk for nutritional and bleeding complications.