Overview of Liver Cancers

Signs, Symptoms of Liver Cancer: Who's at risk? How is it diagnosed?

Overview of Liver Cancers

Medially reviewed by Dr. C.H. Weaver M.D. Medical Editor 8/2018

About Hepatocellular Carcinoma (HCC)

The liver is the largest organ in the body and is responsible for over 500 functions, including the secretion of glucose, proteins, vitamins, and fats; the production of bile; the processing of hemoglobin; and detoxification of numerous substances.

The liver is located on the right side of the abdomen behind the ribs. and has many important functions, including:[1]

  • Removing harmful substances from the blood.
  • Making bile that helps in the digestion of fats from food.
  • Storing glycogen (sugar) that the body can use for energy.

When cancer is identified in the liver, it is important to know whether the cancer started in the liver (primary liver cancer) or spread to the liver from another organ such as the colon or lung. The treatment information in this section focuses on primary liver cancer. If your cancer began in another organ appropriate treatment information will be found by selecting the primary cancer type here:

Benign Liver Tumors

When cells grow abnormally, they can form a mass known as a tumor. Tumors may be benign (not cancer) or malignant (cancer). Benign liver tumors do not spread to other parts of the body, but they may require treatment if they cause symptoms, post a risk of bleeding or rupture, or appear suspicious for cancer. [2] When treatment is required, benign liver tumors can often be surgically removed. Some of the more common types of benign liver tumors are hemangioma, nodular hyperplasia, and adenoma.

Liver Cancer

In contrast to benign liver tumors, liver cancer has the capacity to spread to other parts of the body. There are several different types of liver cancer:

  • Hepatocellular carcinoma is the most common type of primary liver cancer in adults. It begins in the liver cells known as hepatocytes.
  • Cholangiocarcinoma is cancer that develops in the cells that line the bile ducts within the liver.
  • Hepatoblastoma is a rare type of liver cancer that develops in children.
  • Angiosarcoma and Hemangiosarcoma are rare cancers that start in the blood vessels of the liver.

Each year in the United States, there are more than 21,000 new diagnoses of primary liver cancer and more than 18,000 deaths from the disease.[3] Liver cancer is the fifth leading cause of cancer death among U.S. men, and the ninth leading cause of cancer death among U.S. women. Worldwide, more than 700,000 new cases of liver cancer are diagnosed each year.[4]

Because hepatocellular carcinoma accounts for 80-90% of all primary liver cancers,[5] the liver cancer information that follows focuses on this type of cancer.

Signs & Symptoms of Liver Cancer

Liver cancer often causes no symptoms during its early stages. Symptoms that you may experience as the cancer grows include the following:[6]

  • Pain in the upper abdomen on the right side; the pain may extend to the back and shoulder
  • Swollen abdomen (bloating)
  • Weight loss
  • Loss of appetite and feelings of fullness
  • Weakness or feeling very tired
  • Nausea and vomiting
  • Yellow skin and eyes, and dark urine from jaundice
  • Fever

These symptoms can be caused by other conditions and do not necessarily mean that you have cancer, but it’s a good idea to discuss them with your doctor.

Diagnosis of Liver Cancer

When liver cancer is suspected, imaging tests such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) play an important role in confirming the diagnosis. Blood levels of a protein known alpha-fetoprotein (AFP) will also be assessed.[4] Elevated levels of AFP in combination with a liver mass is a common indication of liver cancer. When a liver mass is present but AFP levels are normal, additional imaging procedures may be used to help confirm or exclude the diagnosis of liver cancer.

In contrast to many other types of cancer, biopsy (removal of a sample of tissue) is often not required to diagnosis liver cancer.[4] For most patients (particularly those with cirrhosis), imaging and lab tests provide reliable information about the diagnosis. Furthermore, biopsy of liver cancer carries a small risk of spreading the cancer.[7] Biopsy may be considered, however, in circumstances when there is doubt about the diagnosis.

Screening & Prevention of Liver Cancer

Information about the prevention of cancer and the science of screening appropriate individuals at high risk of developing cancer is gaining interest. Physicians and individuals alike recognize that the best ”treatment“ of cancer is preventing its occurrence in the first place or detecting it early when it may be most treatable.

The chance of an individual developing cancer depends on both genetic and non-genetic factors. A genetic factor is an inherited, unchangeable trait, while a non-genetic factor is a variable in a person’s environment, which can often be changed. Non-genetic factors may include diet, exercise, or exposure to other substances present in our surroundings. These non-genetic factors are often referred to as environmental factors. Some non-genetic factors play a role in facilitating the process of healthy cells turning cancerous (for example, the correlation between smoking and lung cancer) while other cancers have no known environmental correlation but are known to have a genetic predisposition. A genetic predisposition means that a person may be at higher risk for a certain cancer if a family member has that type of cancer.

Heredity or Genetic Factors

A majority of cases of hepatocellular carcinoma can be attributed to environmental factors such as chronic viral infections and heavy alcohol use (discussed in greater detail below). Nevertheless, family history of liver cancer does appear to influence risk of the disease. Certain inherited conditions, such as hereditary hemochromatosis, also increase risk.

Family history of liver cancer: In a study conducted in the United States, individuals with a first-degree family history of liver cancer (liver cancer in a parent, sibling, or child) were roughly four times more likely to develop liver cancer than individuals without such a family history. This increased risk was observed even in the subset of people without viral hepatitis.[1] This study suggests that either genetic factors or shared environmental factors influence the risk of liver cancer.

Hereditary hemochromatosis: Hemochromatosis is a disease in which the body absorbs and stores too much iron. Some of this excess iron is stored in the liver. Hereditary hemochromatosis is one of the most common genetic disorders in the United States, and occurs when an individual inherits a specific genetic mutation from both parents.[2],[3] as well as other health problems.

Environmental or Non-genetic Factors

Hepatocellular carcinoma is often (but not always) preceded by cirrhosis of the liver. In cirrhotic livers healthy liver tissue is replaced by scar tissue. Factors that contribute to liver cirrhosis and liver cancer are chronic infection with hepatitis C or hepatitis B viruses and chronic heavy alcohol use.

Chronic infection with hepatitis B virus (HBV): Chronic infection with HBV is thought to account for more than half the cases of liver cancer that occur worldwide.[4] HBV can be transmitted through contact with infected blood or needles or sexual intercourse with an infected partner, or from an infected mother to her newborn. The likelihood that an HBV infection will become chronic varies by the age at infection. Chronic infection develops in roughly 90% people who are infected as infants and 2-6% of people who are infected as adults. Among those who develop chronic infections, an estimated 15-25% will die prematurely as a result of liver cirrhosis or liver cancer.[5]

Chronic infection with hepatitis C virus (HCV): Chronic infection with HCV is another important risk factor for liver cancer, and is thought to account for some of the increase in liver cancer that has occurred in the United States in recent decades.[6] In North America HCV causes more cases of liver cancer than HBV.[7] HCV is transmitted through contact with infected blood or needles. Sexual transmission and transmission from mother to child during birth are less common routes of infection. Chronic infection develops in a majority of people (70-85%) who are infected with HCV.[8]

Heavy alcohol use: Long-term, heavy alcohol use increases the risk of liver cancer. According to one estimate, consumption of 6-7 drinks per day for more than 10 years increases the risk of liver cancer more than fivefold.[9] The combination of heavy alcohol use with chronic HCV infection results in a particularly high risk. In the United States, heavy alcohol use is thought to account for roughly one-third of all cases of hepatocellular carcinoma.[10]

Diabetes: A combined analysis of previously published studies (most of which focused on type II diabetes) suggests that diabetes is linked with a more than twofold increased risk of hepatocellular carcinoma.[11] It remains possible, however, that diabetes was the result (rather than the cause) of the chronic underlying liver disease.[12] Additional studies are needed to better understand the link between diabetes and hepatocellular carcinoma.

Obesity: Obesity increases the risk of several types of cancer, including endometrial cancer, postmenopausal breast cancer, and colon cancer. More recently, studies have suggested that obesity may also increase the risk of liver cancer.[13],[14] The development of nonalcoholic fatty liver disease may explain some of the link between obesity and hepatocellular carcinoma.

Smoking: Tobacco smoking has been linked with a moderate increase in risk of liver cancer. In a large combined analysis of previously published studies, current smokers were 56% more likely than nonsmokers to develop liver cancer.[15]

Coffee: Several studies have suggested that coffee consumption decreases the risk of liver cancer.[16],[17] It’s uncertain whether this effect is causal or simply the result of a reduction in coffee intake among those with liver disease.

Other exposures: Occupational exposure to vinyl chloride increases the risk of angiosarcoma of the liver (a rare type of liver cancer). Aflatoxin—a toxin produced by fungi that can contaminate food—is an important risk factor for liver cancer in less developed countries.[18]

Prevention of Liver Cancer

Because many cases of hepatocellular carcinoma are linked with heavy alcohol use or chronic infection with HCV or HBV, control of these exposures is an important part of liver cancer prevention.

Hepatitis B vaccination: Routine vaccination of infants against HBV is recommended in the U.S. and several other countries to prevent infection with HBV. Older children and adolescents who were not vaccinated previously, and adults at risk for HBV infection, may also be vaccinated.[19]

Avoidance of HCV: The U.S. blood supply has been screened for HCV since 1992, greatly reducing the risk of infection through blood transfusion. Injection drug use remains an important route of transmission, and injection drug users are advised to avoid sharing needles.[20] Currently, there is no vaccine against HCV.

Limited alcohol consumption: For those who drink, general dietary guidelines recommend no more than two drinks per day for men and no more than one drink per day for women.[21] People with hepatitis or other liver disease may need to avoid alcohol completely. Talk with your doctor about what’s best for you.

Screening and Early Diagnosis

For many types of cancer, progress in cancer screening has offered promise for earlier detection and higher cure rates. The term screening refers to the regular use of certain examinations or tests in persons who do not have symptoms of cancer.

Thus far, there is no conclusive evidence that screening for liver cancer reduces the risk of death from the disease.[22] Nevertheless, some physicians recommend that individuals at high risk of liver cancer—such as those with cirrhosis of the liver—undergo regular screening with tests such as ultrasound of the liver and/or alpha-fetoprotein testing.

Ultrasound: An ultrasound of the liver every 6-12 months may be recommended in order to detect liver cancer at the earliest possible stage in high-risk individuals.[23] If a liver nodule (growth) is detected on ultrasound, the patient may undergo additional testing or more frequent surveillance to establish the diagnosis.[24]

Alpha-fetoprotein testing: Liver cancer can result in elevated blood levels of a protein known as alpha-fetoprotein (AFP), and AFP testing may be used as a screening tool for liver cancer. AFP is not a perfect marker for liver cancer, however, and some researchers have suggested that it should not be the only screening test used.

Strategies to Improve Prevention and Screening

The potential for earlier detection and higher cure rates increases with the advent of more refined screening techniques. In an effort to provide more screening options and perhaps more effective prevention strategies, researchers continue to explore new techniques for the screening and early detection of cancer. Researchers also continue to search for new ways to prevent liver cancer from developing in the first place.

Predicting risk of liver cancer: Although important risk factors for liver cancer have been identified (such as chronic infection with HBV or HCV), many people with these risk factors will never develop liver cancer. Researchers are therefore trying to understand why some groups of patients with chronic liver disease develop liver cancer and others don’t. Answers to this question would improve our understanding of how liver cancer develops (and how it might be prevented), and could also help target screening efforts. As an example of this work, researchers in China developed a risk score to predict risk of liver cancer among individuals with chronic HBV infection.[25] The score incorporated information about age, gender, HBV DNA levels, HBV gene mutations, and cirrhosis. Although it’s unclear whether this score will be applicable outside of this particular population, it represents the progress that is being made.

References:Overview

[1] National Cancer Institute. Adult Primary Liver Cancer Treatment (PDQ®). Available at: (Accessed December 2, 2008).

[2] Ibrahim S, Chen CL, Wang SH et al. Liver resection for benign liver tumors: indications and outcome. American Journal of Surgery. 2007;193:5-9.

[3] American Cancer Society. Cancer Facts & Figures 2017. Available at: (Accessed December 4, 2017).

[4] American Cancer Society. Global Cancer Facts & Figures 2007. Available at: (Accessed January 8, 2009).

[5] Lau W-Y, Lai ECH. Hepatocellular carcinoma: current management and recent advances. Hepatobiliary and Pancreatic Diseases International. 2008;7:237-257.

[6] National Cancer Institute. What You Need to Know About™ Liver Cancer. Available at:

[7] Silva M, Hegab B, Hyde C, et al. Needle track seeding following biopsy of liver lesions in the diagnosis of hepatocellular cancer: a systematic review and meta-analysis. Gut. 2008;57:1592-1596.

References: Screening & Prevention

[1] Hassan MM, Spitz MR, Thomas MB et al. The association of family history of liver cancer with hepatocellular carcinoma: a case-control study in the United States. Journal of Hepatology. Early online publication October 16, 2008.

[2] National Institute of Diabetes and Digestive and Kidney Diseases. Hemochromatosis. Available at: National Digestive Diseases Information Clearinghouse

[3] Elmberg M, Hultcrantz R, Ekbom A et al. Cancer risk in patients with hereditary hemochromatosis and in their first-degree relatives. Gastroenterology. 2003;125:1733-41.

[4] Parkin DM. The global burden of infection-associated cancers in the year 2002. International Journal of Cancer. 2006;118:3030-3044.

[5] Centers for Disease Control and Prevention, Division of Viral Hepatitis. Hepatitis B. Available at:

[6] El-Serg HB, Davila JA, Petersen NJ, McGlynn KA. The continuing increase in the incidence of hepatocellular carcinoma in the United States. Annals of Internal Medicine. 2003;139:817-823.

[7] Raza SA, Clifford GM, Franceschi S. Worldwide variation in the relative importance of hepatitis B and hepatitis C viruses in hepatocellular carcinoma: a systematic review. British Journal of Cancer. 2007;96:1127-34.

[8] Centers for Disease Control and Prevention, Division of Viral Hepatitis. Hepatitis C. Available at:

[9] Morgan TR, Mandayam S, Jamal MM. Alcohol and hepatocellular carcinoma. Gastroenterology. 2004;127:S87-S96.

[0] Hassan MM, Hwang L-Y, Hatten CJ et al. Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus. Hepatology. 2002;36:1206-1213.

[1] El-Serag HB, Hampel H, Javadi F. The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence. Clinical Gastroenterology and Hepatology. 2006;4:369-380.

[2] Chuang S-C, La Vecchia C, Boffetta P. Liver cancer: descriptive epidemiology and risk factors other than HBV and HCV infection. Cancer Letters. Early online publication 2008. doi:10.1016/j.canlet.2008.10.040.

[3] Polesel J, Zucchetto A, Montella M et al. The impact of obesity and diabetes mellitus on the risk of hepatocellular carcinoma. Annals of Oncology.

[4] Ohki T, Tateishi R, Sato T et al. Obesity is an independent risk factor for hepatocellular carcinoma development in chronic hepatitis C patients. Clinical Gastroenterology and Hepatology. 2008;6:459-464.

[5] Gandini S, Botteri E, Iodice S et al. Tobacco smoking and cancer: a meta-analysis. International Journal of Cancer. 2007;122:155-164.

[6] Hu G, Tuomilehto J, Pukkala E et al. Joint effects of coffee consumption and serum gamma-glutamyltransferase on the risk of liver cancer. Hepatology. 2008;48:129-136.

[7] Inoue M, Yoshimi I, Sobue T, Tsugane S. Influence of coffee drinking on subsequent risk of hepatocellular carcinoma: a prospective study in Japan. Journal of the National Cancer Institute. 2005;97:293-300.

[8] Chuang S-C, La Vecchia C, Boffetta P. Liver cancer: descriptive epidemiology and risk factors other than HBV and HCV infection. Cancer Letters. Early online publication 2008. doi:10.1016/j.canlet.2008.10.040.

[9] Centers for Disease Control and Prevention. Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/index.htm (Accessed January 14, 2008).

[0] Recommendations for Prevention and Control of Hepatitis C Virus (HCV) Infection and HCV-Related Chronic Disease. MMWR. 1998;47(RR-19):1-39.

[1] U.S. Department of Health and Human Services and U.S. Department of Agriculture. Dietary Guidelines for Americans, 2005. 6th Edition, Washington, DC: U.S. Government Printing Office, January 2005. Available at: www.healthierus.gov/dietaryguidelines.

[2] National Cancer Institute. Liver (Hepatocellular) Cancer Screening (PDQ®). Available at Liver (Hepatocellular) Cancer Screening

[3] Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208-1236.

[4] Parikh S, Hyman D. Hepatocellular cancer: a guide for the internist. The American Journal of Medicine. 2007;120:194-202.

[5] Yuen M-F, Tanaka Y, Fong D Y-T et al. Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B. Journal of Hepatology. 2009;50:80-88.

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