Liver Cancer

What liver cancer is

The liver filters blood, makes proteins and bile, and stores energy. Primary liver cancer starts in the liver itself. It is different from secondary liver cancer (liver metastases), which spreads to the liver from cancers elsewhere, such as the bowel, and is treated as that original cancer.

Liver cancer is the sixth most common cancer worldwide and one of the leading causes of cancer death, mainly because most cases are found late. In the US, rates have roughly tripled since the 1980s, driven by hepatitis C, alcohol and fatty liver disease.

Types of liver cancer

Symptoms

Early liver cancer rarely causes symptoms. When they appear, they include pain or a lump under the right ribs, weight loss, poor appetite, early fullness, fatigue, jaundice, a swollen belly and itching. For details, see liver cancer symptoms.

Causes and risk factors

Most HCC develops after years of liver inflammation and scarring. The main risk factors are:

• Cirrhosis: from any cause. About 80 to 90 percent of HCC occurs in a cirrhotic liver, and people with cirrhosis have a risk of roughly 1 to 4 percent per year
• Chronic hepatitis B: the leading cause worldwide. It can cause HCC even without cirrhosis
• Chronic hepatitis C: a major cause in the US, Europe and Japan
• Heavy alcohol use: causes alcohol-related liver disease and cirrhosis
• Metabolic dysfunction-associated fatty liver disease (MASLD, formerly NAFLD): linked to obesity and type 2 diabetes, and a fast-growing cause. See fatty liver disease
• Smoking
• Aflatoxin: a toxin from mold on stored grains and nuts, important in parts of Africa and Asia
• Inherited conditions: hemochromatosis, alpha-1 antitrypsin deficiency, Wilson disease
• Male sex and older age

Diagnosis

Imaging and blood tests

• Ultrasound is used for screening and often finds the first suspicious spot
• Multiphase CT or MRI with contrast: in a person with cirrhosis, HCC has a characteristic pattern of lighting up early and washing out later. A typical scan appearance is enough to diagnose HCC without a biopsy
• Alpha-fetoprotein (AFP): a blood marker raised in many HCCs, used alongside imaging and to follow treatment
• Liver function and clotting tests, to judge how well the rest of the liver works

Biopsy

A needle biopsy is done when scans are not typical, when there is no cirrhosis, or to guide certain treatments.

Staging

Doctors stage liver cancer by the number and size of tumors, invasion of blood vessels, spread outside the liver, liver function and the person's fitness. Two common systems are:

• Barcelona Clinic Liver Cancer (BCLC) stages 0 (very early), A (early), B (intermediate), C (advanced) and D (end stage), which also suggest the best treatment for each stage
• Child-Pugh score, which grades liver function as A (good), B or C (poor)

Treatment

Treatment is planned by a multidisciplinary team of hepatologists, surgeons, interventional radiologists and oncologists, and depends heavily on liver function.

Curative treatments for early cancer

• Surgical resection: removing the part of the liver with the tumor, for people with a single tumor and good liver function
• Liver transplant: removes the cancer and the diseased liver. Usually offered for one tumor up to 5 cm, or up to 3 tumors none larger than 3 cm (the Milan criteria), with no vessel invasion or spread
• Ablation: destroying small tumors (usually under 3 cm) with heat from radiofrequency or microwave probes passed through the skin

Treatments for intermediate cancer

• Transarterial chemoembolization (TACE): chemotherapy delivered directly into the artery feeding the tumor, which is then blocked
• Radioembolization (TARE/Y-90): tiny radioactive beads delivered into the tumor's blood supply
• Stereotactic body radiotherapy (SBRT): precisely targeted radiation

Treatments for advanced cancer

• Immunotherapy combinations such as atezolizumab with bevacizumab, or durvalumab with tremelimumab, are now first-line treatment for many people
• Targeted drugs (tyrosine kinase inhibitors) such as lenvatinib, sorafenib, regorafenib and cabozantinib
• Treatment of the underlying liver disease, such as antiviral therapy for hepatitis B or C

Supportive and palliative care

Pain control, treatment of ascites and itching, nutrition support and palliative care improve quality of life and can be given alongside cancer treatment.

Complications

• Liver failure, with jaundice, ascites and confusion
• Bleeding from the tumor or from enlarged veins in the esophagus
• Blockage of the portal vein by tumor
• Spread to the lungs, bones and lymph nodes

Outlook

Survival depends mainly on stage and liver function. In the US, 5-year relative survival is about 37 percent when the cancer is confined to the liver, around 13 percent when it has spread to nearby structures, and a few percent when it has spread to distant organs (American Cancer Society). People with small cancers treated by transplant or resection can do much better, with 5-year survival of 60 to 70 percent or more after transplant. Newer immunotherapy combinations have improved survival in advanced disease. Regular follow-up scans are needed after treatment, because new tumors can develop in a damaged liver.

Prevention

• Hepatitis B vaccination: routine for all US infants and recommended for adults up to age 59, and for older adults at risk. It is one of the most effective cancer-preventing vaccines
• Hepatitis C testing and cure: all US adults should be tested at least once. Modern antiviral pills cure more than 95 percent of infections and lower cancer risk
• Limit alcohol, and stop completely if you have liver disease
• Keep a healthy weight and control diabetes to prevent fatty liver disease
• Do not smoke
• Screening: an ultrasound every 6 months for people with cirrhosis or high-risk hepatitis B

Frequently asked questions

What causes liver cancer?

Most liver cancer develops in a liver damaged by long-term inflammation and scarring. The main causes are cirrhosis, chronic hepatitis B or C, heavy alcohol use and fatty liver disease linked to obesity and diabetes. Smoking, aflatoxin and inherited conditions such as hemochromatosis also raise the risk.

Is liver cancer curable?

Yes, when found early. Small tumors can be cured with surgery, a liver transplant or ablation. That is why people at high risk are screened every 6 months. Advanced liver cancer is usually not curable, but immunotherapy and targeted drugs can control it and extend life.

What is the survival rate for liver cancer?

In the US, about 37 percent of people with cancer confined to the liver are alive 5 years after diagnosis, falling to a few percent once it has spread to distant organs. Outcomes after a transplant for early cancer are much better, with most people alive at 5 years.

What is the difference between primary and secondary liver cancer?

Primary liver cancer starts in the liver, most often as hepatocellular carcinoma. Secondary liver cancer, or liver metastases, has spread from another organ such as the bowel, pancreas or breast. Secondary cancer is more common in the US and is treated according to where it started.

Can liver cancer be prevented?

Many cases can. Hepatitis B vaccination, testing and curing hepatitis C, limiting alcohol, maintaining a healthy weight and not smoking all reduce risk. People with cirrhosis or chronic hepatitis B should have screening ultrasounds every 6 months so cancers are found early.