Liver Cancer

Liver cancer makes up makes up approximately 4.7% of all global cancers, and it is the 6th most commonly diagnosed cancer in the world and the 3rd leading cause of cancer death worldwide. It's estimated that the global burden of liver cancer will reach approximately 1.4 million new cases and 1.3 million deaths per year by 2040 — a 55% increase compared to 2020.

While many cancers spread to the liver, there are also cases where the cancer originates in the liver.

The most common type of primary liver cancer is hepatocellular carcinoma (HCC), which makes up 75-85% of all primary liver cases. Some of the known cases include chronic hepatitis B and C infections well as cirrhosis. HCC is much easier to treat when caught early, however many cancers are caught at advanced stages where survival rates are very low.

What is liver cancer?

The liver is the largest organ in the body and one of the most critical. It’s located in the upper right side of the abdomen, near the ribs between the diaphragm and the stomach. It performs hundreds of critical functions serving as a filter to the blood. It also makes bile, breaks down fat, makes lymph, and processes sugar. Fun fact: The liver can regenerate.

The liver consists of two sections (called right and left lobes), blood vessels, smaller lobes (lobules), hepatic veins, and bile ducts. 

Cholangiocarcinoma (bile duct cancer) is cancer that forms in the network of small ducts that carry bile away from the liver. While similar, it’s not the same as primary liver cancer (HCC).

Liver metastasis is also different from primary liver cancer and treated with a unique treatment plan.

Types of liver cancer

The majority of primary liver cancers (up to 85%) are hepatocellular carcinoma (HCC). This cancer begins in the liver cells called hepatocytes. It’s a fast-growing, aggressive cancer. 

A small subset of HCC cases are called fibrolamellar hepatocellular carcinoma. This usually affects teens and young adults. 

Intrahepatic cancer (IHC) is technically bile duct cancer (cholangiocarcinoma), but it’s inside your liver. Around 10-25% of all primary liver cancer cases are IHC.

Rare types of liver cancer

A few other very rare types of liver cancer include hepatoblastoma (in children) and several forms of sarcoma that occur in the liver’s blood vessels.

Staging liver cancer

Staging helps you understand the size of your tumor, where the cancer is now, and the best treatment plan for your unique situation. Doctors use a variety of staging systems to determine the extent of liver cancer and plan treatment, there is not a single system used in every health care facility.

Learn more about the liver cancer staging systems from the American Cancer Society.

TNM system for liver cancer

The TNM staging system scales solid tumors 0-4 (0-IV). This system is most often used by cancer registries and hospitals for record-keeping and research; however, it's based on post-surgery pathology results and many HCC patients' cancers are not operable.

• Stage I (T1): A single tumor that has not grown into blood vessels. Stage IA is a single tumor 2 cm or smaller; Stage IB is a single tumor larger than 2 cm.
• Stage II (T2): Either a single tumor that has grown into blood vessels, or multiple tumors, none larger than 5 cm.
• Stage III (T3): Multiple tumors, with at least one larger than 5 cm.
• Stage IVA (T4): The tumor has grown into a major branch of the portal or hepatic veins, or has spread to nearby organs other than the gallbladder, or has grown through the outer lining of the liver.
• Stage IVB (any T, M1): The cancer has spread to distant organs such as the lungs or bones (metastatic disease). Lymph node involvement (N1) at any stage also places the cancer in Stage IVB.
  

The Barcelona Clinic Liver Cancer (BCLC) system is the most widely used tool for determining treatment for HCC. BCLC looks at the tumor characteristics (size, number, and whether it has spread into blood vessels), liver function, and performance status (how well you can carry out normal daily activities).

• Stage 0 (Very Early): A single small tumor (under 2 cm), the liver is functioning normally, and you feel well.
• Stage A (Early): One tumor larger than 2 cm, or up to three tumors each under 3 cm. Liver function is normal or near-normal.
• Stage B (Intermediate): Multiple tumors confined to the liver. Liver function is still adequate and the cancer has not spread to blood vessels or beyond the liver.
• Stage C (Advanced): Cancer has grown into liver blood vessels and/or spread to other parts of the body, such as the lungs or lymph nodes.
• Stage D (Terminal): The liver is severely damaged and no longer able to function adequately, regardless of tumor size or location.

What causes liver cancer?

Risk factors put you at a higher risk of getting cancer. Some risk factors can be controlled with lifestyle changes, and others cannot. Older age, smoking, and obesity increase your risk of many cancers.

Up to 80% of primary liver cancers are caused by long-term hepatitis B (HBV) or hepatitis C (HCV) infections — which can lead to scar tissue in the liver (cirrhosis). 

Just because you have a risk factor, that doesn’t mean you will get cancer. 

These are scenarios researchers have found that can increase your risk: 

• Chronic liver disease and cirrhosis
• Hepatitis B or C
• Fatty liver disease
• Alcohol-related liver disease (ALD)
• Type 2 diabetes
• Metabolic dysfunction-associated steatotic liver disease (MASLD)
• Certain inherited syndromes like hemochromatosis and Wilson’s disease
• Too much intake of male hormones or anabolic steroids
• Exposure to arsenic or aflatoxins

Preventing liver cancer

There are several steps you can take toward reducing your risk of liver cancer. Protect yourself from viruses like HBV or HCV; there is a HBV vaccine available for both children and adults and several HCV treatments exist. Patients at risk, particularly those with cirrhosis or chronic HBV, should be on a formal surveillance program where they undergo HCC screening every 6 months with abdominal ultrasound and alpha-fetoprotein (AFP) testing.

As with every cancer, there are steps you can take to adopt a healthy lifestyle and reduce your overall cancer risk, such as maintaining a healthy weight, not smoking, and limiting or eliminating alcohol. 

Learn more about cancer prevention from the American Institute for Cancer Research.

What are some liver cancer statistics? 

Based on GLOBOCAN 2022 data:

• An estimated 684,659 people were diagnosed with HCC globally in 2022, and 597,434 died from the disease.
• HCC accounts for 75–85% of all primary liver cancer cases worldwide.
• Liver cancer is the 3rd leading cause of cancer death globally, (8.3% of all cancer deaths).

According to World Cancer Research Fund:

• China, the US and Japan had the highest number of liver cancer cases.
• The highest incidence and mortality rates are concentrated in East Asia and sub-Saharan Africa, where chronic hepatitis B and C infections are most prevalent.
• China alone accounts for approximately 50% of both new HCC cases and HCC-related deaths worldwide.

According to data published in Biology:

• HCC incidence is 2 to 3 times higher in men than in women globally, with HCC in men typically developing at ages 50–69, while women have a similar incidence across the 50–69 and over-70 age groups.
• The median age at HCC diagnosis varies significantly by region — between 60 and 64 in men in the US, while in sub-Saharan Africa it can be as young as 46 years old.
  

What are my odds of surviving it?

Doctors use what’s called “survival statistics” to understand the likelihood of a patient beating the disease.

Detailed survival statistics are based on where the cancer is located and if it has spread:

Localized

The cancer hasn’t spread

• 45% of cases
• 37.4% alive five years after diagnosis 

Regional

The cancer spread to nearby structures or lymph nodes

• 24% of cases
• 13.2% alive five years after diagnosis 

Distant

The cancer has spread to other organs

• 21% of cases
• 3.5% alive five years after diagnosis 

What types of tests should I expect to undergo?

Doctors will likely use these tests to diagnose primary liver cancer:

• Blood test checking for alpha fetoprotein (AFP)
• Blood tests checking bilirubin, liver enzymes, and tumor markers
• Ultrasound
• Biopsy

Angiogram, CT scan, MRI, PET scan, bone scan, and ERCP test may also be used to identify and diagnose liver cancer.

Ask your doctor about these additional tests—ideally before you begin treatment.

• Biomarker testing
• Genetic testing

I’m facing a diagnosis: What are my next steps?

If you’re facing a diagnosis, the GI Cancers Alliance is here for you. 

If you’re newly diagnosed, work with a multidisciplinary tumor board to create a treatment plan. It’s important to find experts who specialize in primary liver cancer and visit a major cancer center if possible. Some major cancer centers will be able to operate on you, even if you’ve been told you’re inoperable.

For doctors planning liver cancer treatment, an analysis on liver function (Child-Pugh score or MELD score) and performance status will impact the recommended treatment. This evaluates your ability to perform daily tasks and your level of fitness. If you have a lower performance status, you might not be recommended for certain treatments.

Liver cancer treatment plans may include:

• Immunotherapy combinations
• Surgery (possible liver transplant - Milan Criteria will guide eligibility)
• Radiofrequency ablation (RFA)
• Microwave ablation
• Transarterial chemoembolization (TACE)
• Transarterial radioembolization (TARE/Y-90)
• Chemotherapy 
• Radiation 
• Targeted therapy

Today's standard-of-care for HCC has been transformed by clinical trials in the past decade. Ask your doctors about trial eligibility.

ctDNA

A liquid biopsy is a blood test that detects fragments of tumor DNA circulating in the bloodstream, called circulating tumor DNA (ctDNA). In liver cancer, liquid biopsy is emerging as a useful complement to existing monitoring tools.

For many HCC patients, alpha-fetoprotein (AFP) is used as a blood-based tumor marker, but AFP is unreliable in some patients, and some tumors do not produce it at all. ctDNA is being studied as an additional or alternative monitoring tool to help determine if the cancer is responding to treatment. In some cases, it can pick up a recurrence. ctDNA can be tracked over time to assess whether the cancer is responding, potentially providing earlier signals than imaging alone.

ctDNA is also being evaluated as a surveillance tool for high-risk patients with cirrhosis or chronic hepatitis B, where catching a tumor at its earliest stage dramatically improves treatment options.

Liquid biopsy is not yet a universal standard of care in HCC and is still being studied in clinical trials. However, it is increasingly available at major liver cancer centers. Ask your care team whether ctDNA testing may be appropriate for your situation, particularly if AFP has not been a reliable marker for your tumor.

We strongly encourage you to get a second opinion from another trusted doctor so youfeel confident moving forward.