General Information About Adult Primary Liver Cancer

Liver cancer includes two major types: hepatocellular carcinoma (HCC) and intrahepatic bile duct cancer. (Refer to the Cellular Classification of Adult Primary Liver Cancer section of this summary for additional, less-common variances; also refer to the Bile Duct Cancers PDQ summary for more information.)

Incidence and Mortality

Estimated new cases and deaths from liver and intrahepatic bile duct cancer in the United States in 2016:[1]

New cases: 39,230.

Deaths: 27,170.

Hepatocellular carcinoma (HCC) is relatively uncommon in the United States, although its incidence is rising, principally in relation to the spread of hepatitis C virus (HCV) infection[2]. Worldwide, HCC is the sixth most prevalent cancer and the third leading cause of cancer-related deaths[3].


Anatomy of the liver. The liver is in the upper abdomen near the stomach, intestines, gallbladder, and pancreas. The liver has four lobes. Two lobes are on the front and two small lobes (not shown) are on the back of the liver.

Risk Factors

The etiology of HCC is likely multifactorial. The following factors may increase the risk of HCC:

Hepatitis B virus (HBV) infection and hepatitis C virus (HCV) infection: HBV and HCV infections appear to be the most significant causes of HCC worldwide. Chronic HBV infection is the leading cause of HCC in Asia and Africa. HCV infection is the leading cause of HCC in North America, Europe, and Japan[4][5].The annual incidence of HCC in HBV carriers is 0.5% to 1% per year in patients without cirrhosis and 2.5% per year in patients with cirrhosis. The relative risk of HCC is 100 (i.e., carriers of HBV are 100 times more likely to develop HCC than uninfected persons)[6][7].In a single, prospective, population-based study that included 12,008 patients, the presence of anti-HCV positivity conferred a twentyfold increased risk of HCC compared with persons who were anti-HCV negative[8]. HCC may occur in HCV-infected patients with bridging fibrosis, even in the absence of overt cirrhosis[9]. However, the risk is highest among patients with HCV-related established cirrhosis, which has an incidence rate of HCC of 2% to 8% per year[4].

Alcoholic cirrhosis: Several reports suggest that alcoholic cirrhosis is a risk factor for HCC. However, the true incidence of HCC in alcoholic cirrhosis is unknown because most epidemiology reports on this subject were published before the identification of HCV[3].

Metabolic syndrome: The risk factors associated with metabolic syndrome, including insulin resistance, hypertension, dyslipidemia, and obesity, have been recognized as potential causes of nonalcoholic hepatosteatosis, cirrhosis, and HCC. However, no study to date has followed a sufficiently large group of these patients for long enough to describe the incidence of HCC caused by metabolic syndrome[10].

Biliary cirrhosis: The incidence of HCC in stage IV primary biliary cirrhosis is approximately the same as in cirrhosis resulting from hepatitis C[11].

Chronic liver injury: Chronic liver injury probably increases the risk of HCC, especially in patients who develop cirrhosis. The 5-year cumulative risk of developing HCC for patients with cirrhosis ranges between 5% and 30% and depends on etiology (highest in individuals with HCV infection), region or ethnicity (highest in Asians), and stage of cirrhosis[12][13].[Level of evidence: 3iii]

Hemochromatosis: Hemochromatosis is a significant risk factor for HCC and has an increased relative risk twenty times that of the normal population[14].

Aflatoxin B1: Aflatoxin B1 is produced by fungi of the Aspergillus species and is a common contaminant of grain, nuts, and vegetables in some parts of Asia and Africa. Aflatoxin B1 has also been implicated as a cofactor in the etiology of primary liver cancer in carriers of HBV because it increases the neoplastic risk threefold[15].

(Refer to the PDQ summary on Liver (Hepatocellular) Cancer Prevention for more information.)


(Refer to the PDQ summary on Liver (Hepatocellular) Cancer Screening for more information.)

Diagnostic Factors

For lesions that are smaller than 1 cm and are detected during screening in patients at high risk for HCC, further diagnostic evaluation is not required because most of these lesions will be cirrhotic lesions rather than HCC[16].[Level of evidence: 3iii] Close follow-up at 3-month intervals is a common surveillance strategy, using the same technique that first documented the presence of the lesions.

For patients with liver lesions larger than 1 cm who are at risk for HCC, a diagnosis should be established. The tests required to diagnose HCC may include imaging, biopsy, or both.

Diagnostic imaging

In patients with cirrhosis, liver disease, or other risk factors for HCC, and with lesions greater than 1 cm, triple-phase, contrast-enhanced studies (dynamic computed tomography [CT]-scan or magnetic resonance imaging [MRI]) can be used to establish a diagnosis of HCC[17].

A triple-phase CT or MRI assesses the entire liver in distinct phases of perfusion. Following the controlled administration of intravenous contrast media, the arterial and venous phases of perfusion are imaged.

During the arterial phase of the study, HCC enhances more intensely than the surrounding liver because the arterial blood in the liver is diluted by venous blood that does not contain contrast, whereas the HCC contains only arterial blood. In the venous phase, the HCC enhances less than the surrounding liver (which is referred to as the venous washout of HCC), because the arterial blood flowing through the lesion no longer contains contrast; however, the portal blood in the liver now contains contrast.

The presence of arterial uptake followed by washout in a single dynamic study is highly specific (95%–100%) for HCC of 1 to 3 cm in diameter and virtually diagnostic of HCC[18][19][20].[Level of evidence: 3ii] In these cases, the diagnosis of HCC may be established without the need for a second imaging modality, even in the absence of a biopsy confirmation[4][20][21].[Level of evidence: 3ii]

However, if a first imaging modality, such as a contrast-enhanced CT or MRI, is not conclusive, sequential imaging with a different modality can improve sensitivity for HCC detection (from 33% to 41% for either CT or MRI to 76% for both studies when performed sequentially) without a decrease in specificity[19].

If, despite the use of two imaging modalities, a lesion larger than 1 cm remains uncharacterized in a patient at high risk for HCC (i.e., with no or only one classic enhancement pattern), a liver biopsy can be considered[4][20].

Liver biopsy

A liver biopsy may be performed when a diagnosis of HCC is not established by a dynamic imaging modality (three-phase CT or MRI) for liver lesions 1 cm or larger in high-risk patients.

Alpha-fetoprotein (AFP) levels

AFP is insufficiently sensitive or specific for use as a diagnostic assay. AFP can be elevated in intrahepatic cholangiocarcinoma and in some cases in which there are metastases from colon cancer. Finding a mass in the liver of a patient with an elevated AFP does not automatically indicate HCC. However, if the AFP level is high, it can be used to monitor for recurrence.


The natural course of early tumors is poorly known because most HCC patients are treated. However, older reports have described 3-year survival rates of 13% to 21% without any specific treatment[22][23]. At present, only 10% to 23% of patients with HCC may be surgical candidates for curative-intent treatment[24][25]. The 5-year overall survival (OS) rate for patients with early HCC who are undergoing liver transplant is 44% to 78%; and for patients undergoing a liver resection, the OS rate is 27% to 70%[26].

Liver transplantation, surgical resection, and ablation offer high rates of complete responses and a potential for cure in patients with early HCC[4].

The natural course of advanced-stage HCC is better known. Untreated patients with advanced disease usually survive less than 6 months[27]. The survival rate of untreated patients in 25 randomized clinical trials ranged from 10% to 72% at 1 year and 8% to 50% at 2 years[28].

Unlike most patients with solid tumors, the prognosis of patients with HCC is affected by the tumor stage at presentation and by the underlying liver function. The following prognostic factors guide the selection of treatment:

Anatomic extension of the tumor (i.e., tumor size, number of lesions, presence of vascular invasion, and extrahepatic spread).

Performance status.

Functional hepatic reserve based on the Child-Pugh score[27][29][30].

Related Summaries

Other PDQ summaries containing information related to primary liver cancer include the following:

Bile Duct Cancer

Childhood Liver Cancer Treatment

Liver (Hepatocellular) Cancer Screening

Liver (Hepatocellular) Cancer Prevention


1. American Cancer Society: Cancer Facts and Figures 2016. Atlanta, Ga: American Cancer Society, 2016. Available online. Last accessed May 19, 2016.

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