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Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults, and is the most common cause of death in people with cirrhosis.
It occurs in the setting of chronic liver inflammation, and is most closely linked to chronic viral hepatitis infection (hepatitis B or C) or exposure to toxins such as alcohol or aflatoxin. Certain diseases, such as hemochromatosis and alpha 1-antitrypsin deficiency, markedly increase the risk of developing HCC. Metabolic syndrome and NASH are also increasingly recognized as risk factors for HCC.
As with any cancer, the treatment and prognosis of HCC vary depending on the specifics of tumor histology, size, how far the cancer has spread, and overall health.
The vast majority of HCC occurs in Asia and sub-Saharan Africa, in countries where hepatitis B infection is endemic and many are infected from birth. The incidence of HCC in the United States and other developing countries is increasing due to an increase in hepatitis C virus infections. It is more common in males than females for unknown reasons.
Most cases of HCC occur in people who already have signs and symptoms of chronic liver disease. They may present either with worsening of symptoms or may be without symptoms at the time of cancer detection. HCC may directly present with yellow skin, abdominal swelling due to fluid in the abdominal cavity, easy bruising from blood clotting abnormalities, loss of appetite, unintentional weight loss, abdominal pain, nausea, vomiting, or feeling tired.
Microscopically, there are four architectural and cytological types (patterns) of hepatocellular carcinoma: fibrolamellar, pseudoglandular (adenoid), pleomorphic (giant cell) and clear cell. In well-differentiated forms, tumor cells resemble hepatocytes, form trabeculae, cords, and nests, and may contain bile pigment in the cytoplasm. In poorly differentiated forms, malignant epithelial cells are discohesive, pleomorphic, anaplastic, giant. The tumor has a scant stroma and central necrosis because of the poor vascularization.
Treatment of hepatocellular carcinoma varies by the stage of disease, a person's likelihood to tolerate surgery, and availability of liver transplant: Curative intention: for limited disease, when the cancer is limited to one or more areas of within the liver, surgically removing the malignant cells may be curative. This may be accomplished by resection the affected portion of the liver (partial hepatectomy) or in some cases by orthotopic liver transplantation of the entire organ. "Bridging" intention: for limited disease which qualifies for potential liver transplantation, the person may undergo targeted treatment of some or all of the known tumor while waiting for a donor organ to become available. "Downstaging" intention: for moderately advanced disease which has not spread beyond the liver, but is too advanced to qualify for curative treatment. The person may be treated by targeted therapies in order to reduce the size or number of active tumors, with the goal of once again qualifying for liver transplant after this treatment. Palliative intention: for more advanced disease, including spread of cancer beyond the liver or in persons who may not tolerate surgery, treatment intended to decrease symptoms of disease and maximize duration of survival.
Loco-regional therapy (also referred to as liver-directed therapy) refers to any one of several minimally-invasive treatment techniques to focally target HCC within the liver. These procedures are alternatives to surgery, and may be considered in combination with other strategies, such as a later liver transplantation. Generally, these treatment procedures are performed by interventional radiologists or surgeons, in coordination with a medical oncologist. Loco-regional therapy may refer to either percutaneous therapies (e.g. cryoablation), or arterial catheter-based therapies (chemoembolization or radioembolization).
Liver transplantation, replacing the diseased liver with a cadaveric or a living donor liver, plays an increasing role in treatment of HCC. Although outcomes following liver transplant were initially poor (20%-36% survival rate), outcomes have significantly improved with improvement in surgical techniques and adoption of the Milan criteria at US transplantation centers. Expanded Shanghai criteria in China have resulted in overall survival and disease-free survival rates similar to those achieved using the Milan criteria. Studies from the late 2000s obtained higher survival rates ranging from 67% to 91%.
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