Liver cancer, also known as hepatic cancer, primary hepatic cancer, or primary hepatic malignancy, is cancer that starts in the liver. Liver cancer can be primary in which the cancer starts in the liver, or it can be liver metastasis, or secondary, in which the cancer spreads from elsewhere in the body to the liver. Liver metastasis is the more common of the two liver cancers. According to the recent analysis, it is shown that metabolic dysfunction–associated steatotic liver disease, which was previously known as non-alcoholic fatty liver disease (NAFLD) and is now considered as one of the leading causes of hepatocellular carcinoma (HCC) globally, especially in developed nations, due to the increasing prevalence of obesity and type 2 diabetes.
Primary liver cancer is globally the seventh-most frequent cancer and the third-leading cause of death from cancer. In 2018, it occurred in 866,136 people and resulted in 758,725 deaths globally. Higher rates of liver cancer occur where hepatitis B and C are common, including Asia and sub-Saharan Africa. Males are more often affected with hepatocellular carcinoma (HCC) than females. Diagnosis is most frequent among those 65 to 74 years old.
The leading cause of liver cancer is cirrhosis due to hepatitis B, hepatitis C, or alcohol. Other causes include aflatoxin, metabolic dysfunction–associated steatotic liver disease (MASLD; formerly NAFLD) and liver flukes. The most common types are HCC, which makes up 80% of cases and intrahepatic cholangiocarcinoma. The diagnosis may be supported by blood tests and medical imaging, with confirmation by tissue biopsy.
Given that there are many different causes of liver cancer, there are many approaches to liver cancer prevention. These efforts include immunization against hepatitis B, hepatitis B treatment, hepatitis C treatment, decreasing alcohol use, decreasing exposure to aflatoxin in agriculture, and management of obesity and diabetes. Hepatocellular carcinoma (HCC) linked to MASLD can develop even in the absence of cirrhosis, and it occurs more often than virus-induced liver cancers, although cirrhosis still stands as a predominant risk factor overall.
Screening is recommended in those with chronic liver disease. For example, it is recommended that people with chronic liver disease who are at risk for hepatocellular carcinoma be screened every 6 months using ultrasound imaging. As of 2026, clinical guidelines increasingly recommend risk-stratified surveillance for liver disease, incorporating factors such as etiology, stage of fibrosis, age, and comorbidities when determining surveillance strategies.
Because liver cancer is an umbrella term for many types of cancer, the signs and symptoms depend on what type of cancer is present. Symptoms can be vague and broad. Cholangiocarcinoma is associated with sweating, jaundice, abdominal pain, weight loss, and liver enlargement. Hepatocellular carcinoma is associated with abdominal mass, abdominal pain, vomiting, anemia, back pain, jaundice, itching, weight loss and fever.
Treatment options may include surgery, targeted therapy and radiation therapy. In certain cases, ablation therapy, embolization therapy or liver transplantation may be used.
Classification Liver cancer can come from the liver parenchyma as well as other structures within the liver such as the bile duct, blood vessels and immune cells There are many sub-types of liver cancer, the most common of which are described below.
Hepatocellular carcinoma
The most frequent liver cancer, accounting for approximately 75% of all primary liver cancers, is hepatocellular carcinoma (HCC). HCC is a cancer formed by liver cells, known as hepatocytes, that become malignant. In terms of cancer deaths, worldwide HCC is considered the 3rd most common cause of cancer mortalities.
In terms of HCC diagnosis, it is recommended that people with risk factors (including known chronic liver disease, cirrhosis, etc.) should receive screening ultrasounds. If the ultrasound shows a focal area that is larger than 1 centimeter in size, patients should then get a triple-phase contrast-enhanced CT or MRI scan. HCC can then be diagnosed radiologically using the Liver Imaging Reporting and Data System (LI-RADS). There is also a variant type of HCC that consists of both HCC and cholangiocarcinoma.
Intrahepatic cholangiocarcinoma
Cancer of the bile duct (cholangiocarcinoma and cholangiocellular cystadenocarcinoma) account for approximately 6% of primary liver cancers. Intrahepatic cholangiocarcinoma (CCA) is an epithelial cancer of the intra-hepatic biliary tree branches. Intrahepatic CCA is the second leading cause of primary liver cancer. It is more common in men and usually is diagnosed in 60-70 year olds. Risk factors for development of intrahepatic CCA include opisthorchus viverrini infection, Clonorchis sinensis infection, sclerosing cholangitis, choledochal cysts, past procedures of the biliary tree, exposure to thorotrast and dioxins, and cirrhosis. This cancer is usually asymptomatic until the disease has progressed. Symptoms include abdominal pain, night sweats, weight loss, and fatigue. Liver markers that can be increased with intrahepatic CCA are carcinoembryonic antigen (CEA), CA19-9, and CA-125.
Angiosarcoma and hemangiosarcoma
These are rare and aggressive liver cancers, yet are the third most common primary liver cancer making up 0.1-2.0% of primary liver cancer. Angiosarcoma and hemangiosarcoma of the liver come from the blood vessel's endothelial layer. These tumors have poor outcomes because they grow rapidly and metastasise easily. They are also hard to diagnose but are typically suspected on CT or MRI scans that show focal lesions with differing amounts of signal intensity (these tumors have a lot of bleeding or hemorrhage and subsequent dying of tissue (necrosis)). Biopsy with histopathological evaluation yields the definitive diagnosis. While the cause is often never identified (75% are idiopathic), they are associated with exposures to substances such as vinyl chloride, arsenic, thorotrast (e.g. occupational exposure). Radiation is also a risk factor. In adults, these tumors are more common in males; however, in children they are more common in females.
Even with surgery, prognosis is poor with most individuals not living longer than six months after diagnosis. Only 3% of individuals live longer than two years.
Hepatoblastoma
Another type of cancer formed by liver cells is hepatoblastoma, which is specifically formed by immature liver cells. It is a rare malignant tumor that primarily develops in children, and accounts for approximately 1% of all cancers in children and 79% of all primary liver cancers under the age of 15. Most hepatoblastomas form in the right lobe.
Metastasis to liver Many cancers found in the liver are not true liver cancers but are cancers from other sites in the body that have spread to the liver (known as metastases). Frequently, the site of origin is the gastrointestinal tract, since the liver is close to many of these metabolically active, blood-rich organs near to blood vessels and lymph nodes (such as pancreatic cancer, stomach cancer, colon cancer and carcinoid tumors mainly of the appendix), but also from breast cancer, ovarian cancer, lung cancer, renal cancer, prostate cancer.
Children The Children's Oncology Group (COG) has developed a protocol to help diagnose and manage childhood liver tumors.
Causes
Viral infection
Viral infection with hepatitis C virus (HCV) or Hepatitis B virus (HBV) is the chief cause of liver cancer in the world today, accounting for 80% of HCC. Men with chronic HCV or HBV are more likely to develop HCC than women with chronic HCV or HBV; however, the reasons for this gender difference is unknown. HBV infection is also linked to cholangiocarcinoma. The role of viruses other than HCV or HBV in liver cancer is much less clear, even though there is some evidence that co-infection of HBV and hepatitis D virus may increase the risk for HCC.
HBV and HCV can lead to HCC, because these viral infections cause massive inflammation, fibrosis, and eventual cirrhosis occurs within the liver. In addition, many genetic and epigenetic changes are formed in liver cells during HCV and HBV infection, which is a major factor in the production of the liver tumors. The viruses induce malignant changes in cells by altering gene methylation, affecting gene expression, and promoting or repressing cellular signal transduction pathways. By doing this, the viruses can prevent cells from undergoing a programmed form of cell death (apoptosis) and promote viral replication and persistence.
HBV and HCV also induce malignant changes by causing DNA damage and genomic instability. This involves the generation of reactive oxygen species, expression of proteins that interfere with DNA repair enzymes, and HCV induced activation of a mutator enzyme.
Cirrhosis
In addition to virus-related cirrhosis described above, other causes of cirrhosis can lead to HCC. Alcohol intake correlates with risk of HCC, and the risk is far greater in individuals with an alcohol-induced cirrhotic liver. There are a few disorders that are known to cause cirrhosis and lead to cancer, including hereditary hemochromatosis and primary biliary cirrhosis.
Aflatoxin
Aflatoxin exposure can lead to the development of HCC. The aflatoxins are a group of chemicals produced by the fungi Aspergillus flavus (the name comes from A. flavus toxin) and A. parasiticus. Food contamination by the fungi leads to ingestion of the chemicals, which are very toxic to the liver. Common foodstuffs contaminated with the toxins are cereals, peanuts, and other vegetables. The amount (dose) and how long (duration) that a person is in contact with aflatoxin is associated with HCC. Contamination of food is common in Africa, South-East Asia, and China. The mechanism by which aflatoxins cause cancer is through mutations and epigenetic alterations. Aflatoxins induce a spectrum of mutations, including in the p53 tumor suppressor gene, which is a mutation seen in many types of cancers. Mutation in p53, presumably in conjunction with other aflatoxin-induced mutations and epigenetic alterations, is likely a common cause of aflatoxin-induced carcinogenesis.
Nonalcoholic steatohepatitis (NASH) and Nonalcoholic fatty liver (NAFL) NASH and NAFL is beginning to be called a risk factor for liver cancer, particularly HCC. In recent years, there has been a noted increase in liver transplantations for HCC that was attributable to NASH. More research is needed in this area and NASH/NAFL.
Other risk factors in adults High grade dysplastic nodules are precancerous lesions of the liver. Within two years, there is a risk for cancer arising from these nodules of 30–40%. Obesity and metabolic syndrome have emerged as an important risk factor, as they can lead to steatohepatitis. Diabetes increases the risk for HCC. Smoking increases the risk for HCC compared to non-smokers and previous smokers. There is around 5-10% lifetime risk of cholangiocarcinoma in people with primary sclerosing cholangitis. Liver fluke infection increases the risk for cholangiocarcinoma, and this is the reason why Thailand has particularly high rates of this cancer. Choledochal cysts, Caroli's disease, and congenital hepatic fibrosis are associated with cholangiocarcinoma development. Genetic conditions: untreated hereditary hemochromatosis, alpha-1-antitrypsin deficiency, glycogen storage diseases, porphyria cutanea tarda, Wilson's disease, tyrosinemia have all been associated with development of HCC. Oral contraceptive pill: There is insufficient evidence to label oral contraceptives as a risk factor. However, recent studies have found that taking oral contraceptives for longer than five years is associated with HCC.
Children