Hepatocellular Carcinoma (HCC)

What is hepatocellular carcinoma?

HCC grows from hepatocytes, the cells that do most of the liver's work. It is different from cancer that spreads to the liver from elsewhere (liver metastases), which is more common in many countries, and from bile duct cancer (cholangiocarcinoma). For an overview of all types, see liver cancer.

Most HCC arises after years of liver injury. Inflammation and repeated cell regeneration cause genetic damage, leading first to precancerous nodules and then cancer. About 80 to 90% of cases occur in people with cirrhosis. Worldwide, HCC is among the leading causes of cancer death, and it is 2 to 3 times more common in men.

Causes and risk factors

Symptoms

Small tumors usually cause no symptoms. When symptoms appear, the cancer is often advanced:

• A dull ache or pain in the upper right belly, sometimes spreading to the right shoulder
• A lump or fullness under the right ribs (enlarged liver)
• Unexplained weight loss, poor appetite and feeling full early
• Fatigue and weakness
• Jaundice: yellow skin and eyes, dark urine, pale stools, itching
• Ascites: a swollen belly from fluid
• In someone with known cirrhosis: sudden worsening of liver function, confusion or bleeding

A tumor can occasionally rupture and bleed into the belly, causing sudden severe pain and collapse.

Screening (surveillance) for HCC

Because early HCC is silent and curable, guidelines from the AASLD and EASL recommend a liver ultrasound every 6 months, often with an alpha-fetoprotein (AFP) blood test, for:

• All adults with cirrhosis who would be fit for treatment
• People with chronic hepatitis B at high risk even without cirrhosis, including Asian men over 40, Asian women over 50, people of African origin, and those with a family history of HCC

When ultrasound views are poor, for example with obesity, a CT or MRI may be used instead. Surveillance clearly increases the share of cancers found at a curable stage.

How HCC is diagnosed

1. Multiphase CT or MRI with contrast: HCC has a characteristic pattern: it lights up strongly when contrast arrives in the arteries ("arterial enhancement") and fades faster than surrounding liver ("washout"). In a person with cirrhosis, a lesion of 1 cm or more with this pattern is classified as definite HCC using the LI-RADS system, without needing a biopsy.
2. AFP: raised in many but not all HCCs. A normal AFP does not rule it out.
3. Biopsy: when imaging is not typical, or in a liver without cirrhosis.
4. Assessing the liver: blood tests (bilirubin, albumin, clotting) give a Child-Pugh score, which shows how much liver reserve remains for treatment.
5. Staging scans: CT of the chest and sometimes a bone scan.

Staging: the BCLC system

Most centers use the Barcelona Clinic Liver Cancer (BCLC) system, which combines tumor size and number, liver function and general fitness to guide treatment.

Treatment

Curative treatments

• Surgical resection: removing part of the liver. Best for single tumors in people with good liver function and no significant portal hypertension.
• Liver transplant: treats both the cancer and the underlying cirrhosis. Usually offered within the Milan criteria (one tumor up to 5 cm, or up to 3 tumors each up to 3 cm, without vessel invasion).
• Ablation: a needle placed through the skin destroys the tumor with heat (radiofrequency or microwave). Very effective for tumors under 3 cm.

Treatments that control the cancer

• Transarterial chemoembolization (TACE): chemotherapy and blocking particles injected into the artery feeding the tumor.
• Radioembolization (TARE or Y-90): tiny radioactive beads delivered the same way.
• Stereotactic body radiotherapy: precise high-dose radiation.

Systemic treatment for advanced HCC

• Immunotherapy combinations are now first-line, for example atezolizumab with bevacizumab, or durvalumab with tremelimumab.
• Targeted tablets such as sorafenib, lenvatinib, regorafenib and cabozantinib.
• Treatment of the underlying liver disease (antivirals for hepatitis B, stopping alcohol) remains important.

Palliative care helps with pain, itching, fluid and fatigue at every stage, not only at the end of life.

Outlook

Survival depends on stage and liver function. Overall US five-year survival for liver cancer is around 20%, but it is much higher, often 60 to 80%, for small tumors treated by transplant, resection or ablation. HCC can recur in the remaining liver after resection or ablation, so scans continue every few months for at least 2 years.

Prevention

• Hepatitis B vaccination, which has sharply reduced HCC in vaccinated populations
• Testing and treatment for hepatitis B and C
• Limiting alcohol
• Managing weight, diabetes and fatty liver disease
• Coffee drinking is linked to lower risk in observational studies
• Regular ultrasound surveillance if you have cirrhosis or high-risk hepatitis B

Frequently asked questions

What is the difference between hepatocellular carcinoma and liver cancer?

Liver cancer is the umbrella term. Hepatocellular carcinoma is the most common type of primary liver cancer, starting in hepatocytes. Other types include cholangiocarcinoma (bile duct cancer) and, in children, hepatoblastoma. Cancer that spreads to the liver from the bowel or breast is called liver metastases, not HCC.

What are the early signs of hepatocellular carcinoma?

Early HCC usually causes no symptoms at all, which is why at-risk people need ultrasound screening. Later signs include a dull ache under the right ribs, weight loss, poor appetite, feeling full quickly, a swollen belly, jaundice, and sudden worsening in someone with cirrhosis.

Who should be screened for HCC?

Adults with cirrhosis from any cause, and people with chronic hepatitis B at high risk even without cirrhosis, should have a liver ultrasound every 6 months, often with an AFP blood test. Your liver specialist will advise whether you qualify based on your cause of liver disease and age.

Can hepatocellular carcinoma be cured?

Yes, when found early. Removing the tumor, destroying it with ablation, or a liver transplant can cure small HCCs. Transplant has the best long-term results because it also removes the diseased liver. Advanced HCC is usually not curable but can be controlled with immunotherapy and targeted medicines.

What is the survival rate for HCC?

Overall five-year survival for liver cancer in the US is around 20%. For HCC found early and treated with transplant, resection or ablation, five-year survival is often 60 to 80%. Survival with advanced disease is shorter but has improved with modern immunotherapy combinations.