Liver Cancer

Primary liver cancer begins in the liver itself. The major types include:

Hepatocellular carcinoma (HCC), which begins in liver cells and is the most common type.

Intrahepatic cholangiocarcinoma (ICC), which develops from bile ducts within the liver and has a different diagnostic and treatment pathway.

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA), which contains features of both HCC and cholangiocarcinoma.

Primary liver cancer is different from cancer that has spread to the liver from another organ. For example, colorectal cancer that spreads to the liver is still treated as metastatic colorectal cancer rather than primary liver cancer.

The information below focuses mainly on HCC.

HCC often develops in the setting of long-term liver injury, although not every patient has cirrhosis.

Major risk factors include:

• Chronic hepatitis B virus (HBV) infection

• Chronic hepatitis C virus (HCV) infection

• Cirrhosis

• Long-term heavy alcohol use

• Metabolic dysfunction-associated steatotic liver disease and other chronic liver diseases

• Certain environmental exposures, including aflatoxins

• Some inherited or metabolic liver disorders

People with chronic hepatitis B can develop HCC even without cirrhosis.

For people at increased risk, treating the underlying liver disease and undergoing regular liver cancer surveillance can help detect cancer earlier.

Early HCC often causes no noticeable symptoms and may be detected during surveillance for chronic liver disease or through imaging.

As the disease progresses, symptoms may include:

• Pain or discomfort in the upper right abdomen

• Abdominal swelling

• Loss of appetite

• Fatigue

• Unexplained weight loss

• Nausea or feeling full quickly

• Yellowing of the skin or eyes

• Fluid buildup in the abdomen or swelling of the legs

• A mass in the upper abdomen

Some of these symptoms can also result from cirrhosis or other chronic liver disease. New or worsening symptoms in someone with liver disease should be medically evaluated.

Diagnosing HCC involves more than identifying a tumor. Doctors also need to determine the extent of the cancer and evaluate liver function, because both strongly influence treatment decisions.

Blood tests may include liver and kidney function, a complete blood count, coagulation tests, and alpha-fetoprotein (AFP).

AFP can support diagnosis and monitoring in some patients, but an elevated AFP level alone does not diagnose HCC, and a normal AFP level does not rule it out.

Multiphasic contrast-enhanced CT and MRI are important for diagnosis and staging. In patients at high risk for HCC, such as those with cirrhosis or chronic hepatitis B, characteristic imaging findings may allow HCC to be diagnosed without a biopsy.

Ultrasound is commonly used for surveillance in high-risk populations. A suspicious lesion generally requires further evaluation with contrast-enhanced CT or MRI.

A liver biopsy is not required for every patient. It may be needed when imaging findings are not typical, when the patient does not fit a standard high-risk population, or when another type of cancer needs to be distinguished.

Treatment for HCC is determined by both the cancer and the condition of the liver. Decisions take into account tumor number and location, vascular invasion or metastasis, liver function, portal hypertension, and overall health. Multidisciplinary care is especially important in HCC.

Surgical Resection

Surgery can offer a chance for long-term disease control or cure in selected patients with localized tumors and adequate liver function.

Eligibility is based on more than tumor size or number. Doctors also consider the amount and function of the liver that would remain after surgery, portal hypertension, and overall health.

Some patients whose tumors are initially considered unresectable may become candidates for surgery after successful systemic or locoregional treatment.

Liver Transplantation

Liver transplantation is another treatment with curative potential for carefully selected patients.

It removes both the tumor and the diseased liver and can be particularly valuable for patients with cirrhosis whose tumors meet transplant criteria.

Transplantation is not simply an alternative for anyone who cannot undergo resection. Tumor burden, vascular invasion, extrahepatic spread, liver function, and donor availability all need to be considered.

Ablation

Radiofrequency ablation and microwave ablation can provide potentially curative local treatment for selected patients with small, early-stage HCC.

Treatment choice depends on tumor size, number, location, surrounding structures, and liver function.

Transarterial Therapy

Transarterial chemoembolization (TACE) is an important treatment for selected patients whose disease is largely confined to the liver but is not suitable for surgery, transplantation, or ablation.

Other liver-directed approaches, including hepatic arterial infusion chemotherapy in selected settings, may also be used as part of multidisciplinary treatment.

Radiation Therapy

Modern radiation techniques such as stereotactic body radiation therapy (SBRT) can be used for selected localized tumors that cannot be treated with surgery or ablation and may also help control locally advanced or metastatic disease.

Systemic Therapy

Systemic treatment has changed substantially in recent years.

For unresectable or advanced HCC, important first-line options now include combinations of immunotherapy and anti-angiogenic therapy, as well as dual immune checkpoint blockade. Examples include atezolizumab plus bevacizumab and durvalumab plus tremelimumab.

Multikinase inhibitors such as lenvatinib and sorafenib remain appropriate options for some patients.

Later-line treatment depends on previous therapy, liver function, tumor characteristics, and locally available therapies.