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What is Hepatocellular carcinoma?
Hepatocellular carcinoma is a tumor that is relatively uncommon in the United States, although its incidence is rising, principally in relation to the spread of hepatitis C infection. It is the most common cancer in some parts of the world, with more than one million new cases diagnosed each year. Hepatocellular carcinoma is potentially curable by surgical resection, but surgery is the treatment of choice for only the small fraction of patients with localized disease. Prognosis depends on the degree of local tumor replacement and the extent of liver function impairment. Therapy other than surgical resection is best administered as part of a clinical trial. Such trials evaluate the efficacy of systemic or infusional chemotherapy, hepatic artery ligation or embolization, percutaneous ethanol injection, radiofrequency ablation, cryotherapy, and radiolabeled antibodies, often in conjunction with surgical resection and/or radiation therapy. In some studies of these approaches, long remissions have been reported. A few patients may be candidates for liver transplantation, but the limited availability of livers for transplantation restricts the use of this approach.[4] Hepatocellular carcinoma can coexist with bile duct cancer (cholangiocarcinoma).
Risk factors
Hepatocellular carcinoma is associated with cirrhosis in 50% to 80% of patients; 5% of cirrhotic patients eventually develop hepatocellular cancer, which is often multifocal.
Hepatitis B infection and hepatitis C infection appear to be the most significant causes of hepatocellular carcinoma worldwide, particularly in patients with continuing antigenemia and in those who have chronic active hepatitis. A series found that male patients older than 50 years who have both hepatitis B and hepatitis C infection may be at particularly high risk for hepatocellular cancer. [Level of evidence: 3iiiDiii] There is evidence that patients with both hepatitis B and hepatitis C infection who consume more than 80 grams of alcohol per day have an increased risk of developing cancer (odds ratio [OR] = 7.3) when compared to patients who abstain from alcohol. Additionally, having a first-degree relative with hepatitis B plus hepatocellular carcinoma is associated with an increased risk (OR = 2.41) for family members who are hepatitis B carriers.
Aflatoxin has also been implicated as a factor in the etiology of primary liver cancer in parts of the world where this mycotoxin occurs in high levels in ingested food. Workers who were exposed to vinyl chloride before controls on vinyl chloride dust were instituted developed sarcomas in the liver, most commonly angiosarcomas. Other sarcomas of smooth muscular and vascular origin are also found.
The primary symptoms of hepatocellular carcinoma are those of a hepatic mass. Among patients with underlying cirrhotic disease, a progressive increase in alpha-fetoprotein (AFP) and/or in alkaline phosphatase or a rapid deterioration of hepatic function may be the only clue to the presence of the neoplasm. Infrequently, patients with this disease have polycythemia, hypoglycemia, hypercalcemia, or dysfibrinogenemia.
Prognostic factors
The biologic marker AFP is useful for the diagnosis of this neoplasm. By a radioimmunoassay technique, 50% to 70% of patients in the United States who have hepatocellular carcinoma have elevated levels of AFP. However, patients with other malignancies (germ cell carcinoma and, rarely, pancreatic and gastric carcinoma) also demonstrate elevated serum levels of this protein. AFP levels have been shown to be prognostically important, with the median survival of AFP-negative patients significantly longer than that of AFP-positive patients. Other prognostic variables include performance status, liver functions, and the presence or absence of cirrhosis and its severity in relation to the Child-Pugh classification.
Patients scheduled for possible resection require preoperative assessment with angiography in conjunction with helical computed tomographic (CT) scan or magnetic resonance imaging (MRI) with magnetic resonance angiography; these scans have obviated the need for angiography in most patients. Information on the arterial anatomy is helpful for the operating surgeon and may eliminate some patients from consideration for resection. The presence of tumor thrombi in the hepatic veins, the inferior vena cava, or the portal vein can significantly alter treatment approaches. Dynamic CT and MRI scans can document the relationship of the tumor to the hepatic and portal veins (and, on occasion, involvement of these structures), delineating tumors for which the chances for surgical cure are remote. Laparoscopic evaluation may detect metastatic disease, bilobar disease, or inadequate liver remnant, and therefore obviate the need for open surgical exploration.
Cellular Classification
Malignant tumors of the liver are primarily adenocarcinomas, with 2 major cell types: hepatocellular and cholangiocarcinoma.
Histologic classification is as follows:
- Hepatocellular carcinoma (liver cell carcinoma).
- Hepatocellular carcinoma (fibrolamellar variant). [Note: The fibrolamellar variant is important because an increased proportion of these patients may be cured if the tumor can be resected. It is more frequent in young women. It also generally exhibits a slower clinical course than the more common hepatocellular carcinoma.]
- Cholangiocarcinoma (intrahepatic bile duct carcinoma).
- Mixed hepatocellular cholangiocarcinoma.
- Undifferentiated.
Hepatoblastoma rarely occurs in adults.
National Cancer Institute
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