Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer (85%-to-90% of all liver cancers) and occurs when liver cells (hepatocytes) develop abnormalities and turn cancerous. Hepatocellular carcinoma most frequently occurs in people with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections or non-alcoholic fatty liver disease (NAFLD). Most people diagnosed with hepatocellular carcinoma also have cirrhosis, a chronic liver disease that causes scarring (fibrosis) in the liver, which is a type of chronic liver damage. While rare in the U.S., the number of people diagnosed with hepatocellular carcinoma has increased in the past few decades. In other parts of the world, especially Asia, hepatocellular carcinoma occurs much more frequently due to an increased exposure to hepatitis B virus, cancer-causing chemicals, and parasitic infections (schistosomiasis). Primary hepatocellular carcinoma is cancer that originates in the liver. Secondary liver cancers occur when the cancer has spread to the liver from another part of the body, usually the breast, colon, lung, or pancreas and are different than primary hepatocellular carcinoma, which may begin as a tumor that eventually spreads to other areas of the liver.

Alternative names for liver cancer include hepatocellular carcinoma, hepatoma, hepatic cancer, and liver cell carcinoma.

The exact cause of hepatocellular carcinoma is unknown; however, the disease is thought to have more than one cause. Several risk factors increase the chances of developing hepatocellular carcinoma, such as chronic hepatitis B virus (HBV) infection or chronic hepatitis C virus (HCV) infection, both of which cause cirrhosis (liver scarring/fibrosis) that can develop into hepatocellular carcinoma, excessive alcohol intake, and fatty liver diseases, such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (severe fatty liver disease; NASH). Smoking cigarettes is a major risk factor, while obesity and diabetes are additional lower-risk factors for developing hepatocellular carcinoma. Eating foods with aflatoxins, which fungi produce, exposure to chemicals, such as vinyl chloride and Thorotrast (previously used in X-rays), using anabolic steroids, exposure to arsenic, exposure to parasites (schistosomiasis) in Asia, Africa, and South America, having a rare metabolic or genetic disorder, such as autoimmune hepatitis, alpha-1 antitrypsin deficiency, hemochromatosis, porphyria cutanea tarda, primary biliary cholangitis, tyrosinemia, Wilson’s disease, hemochromatosis, or being of certain races/ethnicities, such as Asian American, Pacific Islander, American Indian, Alaska Native, Hispanic/Latinos, or African American, all increase the risk of hepatocellular cancer. High rates of hepatitis B virus (HBV) infection in Asia have increased the rates of hepatocellular cancer in those countries. In the U.S., hepatitis C virus more commonly leads to hepatocellular carcinoma. Metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) are also associated with obesity and are a significant cause of hepatocellular carcinoma. It is estimated that nearly 30% of Americans have non-alcoholic fatty liver disease, which can then become a severe form of fatty liver disease known as non-alcoholic steatohepatitis (NASH). In turn, non-alcoholic steatohepatitis can develop into hepatocellular carcinoma.

Early hepatocellular carcinoma frequently does not cause any symptoms; however, individuals may experience symptoms from underlying liver disease, such as cirrhosis (liver scarring/fibrosis), as well as mild-to-moderate pain in the upper right abdomen, decreased appetite, excessive itching, fatigue, unexplained weight loss, fever, diarrhea, abnormal bruising or bleeding, or the appearance of a mass in the upper abdomen. As the liver becomes increasingly overworked (decompensated), symptoms may appear such as ascites (abdominal fluid build-up); splenomegaly (enlarged spleen); portal hypertension (high blood pressive in the great main vein of the liver;  jaundice (yellowing of the skin, eyes, and mucous membranes; and hepatic encephalopathy (build up of toxins in the brain) that causes confusion, memory loss, personality changes, and coma. Hepatocellular carcinoma can also spread (metastasize) to other areas of the body, such as the lungs or bones, causing difficulty breathing (dyspnea) or bone pain.

Treatments for hepatocellular carcinoma are determined by the extent of the cancer and tumor size. Treatments for hepatocellular carcinoma include surgery (resection), ablation therapy, chemotherapy, radiation therapy, targeted drug therapy, immunotherapy, and liver transplant. Surgery (Resection) – Early-stage hepatocellular carcinoma, in patients whose liver is functioning normally, may be treated with removal of the cancer (resection) as well as a small amount (margins) of healthy tissue surrounding the cancer. Ablation therapy – Ablation therapy (cryoablation, radiofrequency, or microwave ablation) uses extreme hot or cold to kill cancer cells and may be an option for patients with unresectable hepatocellular carcinoma. Chemotherapy (Chemoembolization) – Trans-Arterial Chemoembolization (TACE) is a procedure where a catheter is inserted through blood vessels into the liver through which chemotherapy drugs are delivered directly to the cancer. Radiation therapy – Stereotactic body radiotherapy (SBRT), where several beams of radiation are directed at the cancer, or X-rays or protons may be used for unresectable hepatocellular carcinoma. Targeted drug therapy – Targeted drug therapy, such as the drug, sorafenib, designed to attack cancer cells’ ability to reproduce and survive, may be used in advanced hepatocellular carcinoma to slow the progress of the disease. Immunotherapy – Immunotherapy drugs enlist the body’s immune system to kill the cancer cells and may be used for advanced hepatocellular carcinoma. Liver transplant – In early hepatocellular carcinoma that has not spread (metastasized), the diseased liver with hepatocellular carcinoma may be surgically removed and replaced with a donor liver. However, liver transplants may only be offered to select patients based on select criteria. Clinical trials – Physicians may recommend that a patient with hepatocellular carcinoma participate in a clinical trial, during which they may be given access to new, experimental treatments.  Palliative care – If the hepatocellular carcinoma is unresectable (cannot be removed with surgery) or has metastasized, a cure is unlikely, in which case, palliative care, which is designed to improve the patient’s quality of life, is recommended.

There are a variety of support groups for individuals with hepatocellular carcinoma: American Liver Foundation - https://liverfoundation.org/for-patients/resources/support-groups/ CancerCare - https://www.cancercare.org/publications/238-coping_with_liver_cancer Cancer Support Community - https://www.cancersupportcommunity.org/liver-cancer

The outcomes for hepatocellular carcinoma depend on whether the cancer can be removed by surgery and whether the cancer has spread. Hepatocellular carcinoma that is diagnosed early may respond to curative treatments. For late-stage hepatocellular carcinoma, there may not be any curative treatments, in which case the focus is on improving the patient’s quality of life.

Complications of hepatocellular carcinoma include abdominal fluid build-up, tumor rupture, or hemorrhage into the abdomen. Some patients with hepatocellular carcinoma may develop paraneoplastic syndrome, in which the body’s immune system damages the central nervous system. Cancer treatment-related complications may also occur, for which treatment is an essential part of cancer care.

If you experience any persistent symptoms (longer than two weeks), such as abdominal discomfort or distention (bloating), unexplained weight loss, jaundice (yellowing of skin, eyes, and mucous membranes), darkened urine, persistent itching, fever, abdominal pain in the right upper abdomen, nausea or vomiting, make an appointment with a gastroenterologist as soon as possible. Liver cancer is frequently detected during a screening for an underlying disease. Patients often complain of symptoms related to a liver disease, and upon investigation, the cancer is discovered.

The risk of hepatocellular cancer may be reduced by both preventing and treating viral hepatitis infections. Vaccinations to prevent hepatitis B virus (HBV) infection should be administered in children to lower the risk of liver cancer later in life. Avoid drinking excessive amounts of alcohol. Patients who have hepatitis B virus (HBV), hepatitis C virus (HCV), or cirrhosis (liver scarring/fibrosis) should be screened for liver cancer. Individuals with hemochromatosis (excessive iron) may need periodic screening for liver cancer. Hepatocellular carcinoma is often discovered during examination for other underlying disease, or when patients complain of liver disease-related symptoms. Early detection of hepatocellular carcinoma may lead to being offered curative treatment.