Liver cancer is a type of cancer that affects the tissue of the liver. When cancer begins in the liver, cancer cells begin growing at abnormal rates, destroying and stealing important nutrients from healthy cells, and forming tumors that interfere with normal liver function.

The liver is the largest glandular organ in the body, and is responsible for detoxifying various metabolites, producing biochemicals that are needed for digestion and growth, and synthesizing proteins.

In addition, this organ acts as storage for vital nutrients such as glucose and vitamins, which help the body remain nourished for longer periods of time after eating. It sits in the upper quadrant of the abdomen, just below the diaphragm and above the stomach.

Liver cancer can generally be categorized in two ways, as primary or secondary.

Primary liver cancer refers to a condition where cancer starts in the liver, while secondary liver cancer is one that starts in another region of the body (such as lung, esophagus, or breast) and at a later time moves to the liver.

The American Cancer Society estimates that in 2020, there will be 42,810 new cases of primary liver cancer in the United States. While treatments to fight this disease are constantly improving, the incidence of primary liver cancer has tripled in the last 40 years alone 1.

Signs and Symptoms of Liver Cancer

While having one or more symptoms of liver cancer doesn’t necessarily mean that you have liver cancer, it is still important to be aware of the general symptoms and signs, and check up with a doctor to verify what is causing them. Other conditions and health issues may exhibit some of the symptoms, and it will not be possible to tell their origin with certainty without being examined by a physician.

In the early stages of primary liver cancer, most people do not experience any symptoms or signs.

When they appear, common symptoms may include:

  • Weight loss
  • Appetite loss
  • General fatigue and weakness
  • Abdominal pain, discomfort or tenderness (in the upper region)
  • Abdominal swelling
  • White, chalky stools
  • Vomiting
  • Nausea
  • Bruising or excessive bleeding
  • Yellow discoloration of the skin and the whites of the eyes

Types of Liver Cancer

Primary Liver Cancer

A cancer that begins in the liver is termed as primary liver cancer. There is more than one type of primary liver cancer.

Hepatocellular Carcinoma (HCC): This is the most frequently occurring form of liver cancer, and accounts for the majority of cases in adults.

Hepatocellular carcinoma cancers vary in their patterns of growth and how they spread within the liver and body.

HCC can begin as a single tumour that expands in size and only spreads to other parts of the liver in later stages of the disease. In another HCC growth pattern, the disease seems to begin as multiple small cancer nodules within the liver. This is most often observed in individuals affected by cirrhosis, and is the pattern that is most commonly seen in the U.S.

Intrahepatic Cholangiocarcinoma (Bile Duct Cancer): Between 10% to 20% of cancers that begin in the liver are intrahepatic cholangiocarcinomas 2.

Also known as bile duct cancer, this cancer starts out in the cells that line the small bile ducts (tubes that transfer bile to the gallbladder). However, the majority of cholangiocarcinomas begin in the bile ducts that are outside of the liver.

Angiosarcoma and Hemangiosarcoma: These cancers are considered rare, and start in the cells lining the blood vessels in the liver.

Individuals that have been exposed to thorium dioxide (Thorotrast) or vinyl chloride (odorless, flammable gas used to create vinyl products) are at a higher risk of developing this type of cancer 3.

Other noted causes include exposure to radium or arsenic, and individuals with hereditary hemochromatosis are also at higher risk.

In around half of the cases a likely cause for this type of cancer is not identified.

Secondary Liver Cancer

The majority of the time when cancer is found in the liver, it does not initially begin in the organ, but is rather metastasized (spread) from another part of the body, such as the colon, stomach, breast, pancreas, or lung.

If the cancer does not initially begin in the liver, it is classified as secondary liver cancer.

For example, breast cancer that metastasizes to the liver is called breast cancer with spread to the liver. It is also treated as breast cancer, rather than liver cancer.

Liver Cancer Stages

Liver cancer can be classified into different stages which describe how the disease has progressed in terms of its severity and spread in the body (often referred to as the extent of cancer).

Doctors use information that is gathered from different tests and exams (such as blood or imaging tests) to determine the correct cancer stage in their patients. Diagnosing the stages of liver cancer accurately is extremely important, as it will be used to determine the most appropriate treatment and estimate the outcome for the patient.

Barcelona Clinic Liver Cancer (BCLC) Staging System

There are a variety of staging systems for liver cancer, and one of the most common is the Barcelona Clinic Liver Cancer staging system, which applies only to hepatocellular carcinoma.

This staging system refers to the size and number of the tumors in the liver, as well as the overall well-being of the patient.

It includes 5 stages - starting stage 0, and followed by stages A, B, C and D 4.

Stage 0: In the very early stage the size of the tumor is less than 2cm (0.79 inches). The patient feels well, and the liver is functioning normally.

Stage A: In the early stage the patient has either one tumor regardless of size, or up to 3 tumors that are less than 3cm (1.18 inches). The patient feels well, and the liver is functioning normally.

Stage B: In the intermediate stage there are more than 3 tumors in the liver. The patient feels well, and the liver is functioning normally.

Stage C: In the advanced stage, the cancer spreads into the blood and the lymph nodes, or into other organs in the body. Alternatively, the person does not feel well and is less active.

Stage D: In the end stage of the disease, the patient has severe liver damage or does not feel well and needs assistance in being looked after.

Causes & Risk Factors of Liver Cancer

The exact cause of liver cancer is not known, although multiple risk factors can contribute to developing the disease.

It is important for individuals to be aware of the risks associated with general factors (such as their race, gender or age), as well as understand how their lifestyle choices increase or decrease the risk of developing the disease.

The National Comprehensive Cancer Center suggests that individuals that are at high-risk of developing liver cancer are recommended to get blood tests and ultrasounds examinations every 6 to 12 months.

Common liver cancer causes & risk factors include:

Age: In the U.S., liver cancer occurs most frequently in individuals over the age of 60. The average on-set age for liver cancer is 63 5.

Race/Ethnicity: In the U.S., Asian Americans and Pacific Islanders are at the highest risk of liver cancer. These groups are followed by American Indians/Alaska Natives, Hispanics/Latinos, African Americans, and Caucasians.

This increased risk in Asian Americans is likely due to higher rates of hepatitis (particularly hepatitis B) in this group.

Gender: Men are about 3 times more likely to develop liver cancer when compared to women.

It is estimated that in 2020, 41,820 adults in the U.S. will be diagnosed with liver cancer, out of which 30,170 will be men and 12,640 women 6. It is not entirely clear whether the higher prevalence in men is due to genetic susceptibility or because of behaviors that negatively affect the risk factors described below.

Tobacco: Smoking tobacco is correlated with an increase in the risk of developing liver cancer - the more and longer an individual smokes, the greater the risk of developing the disease becomes.

Alcohol: Consuming more than 3 drinks per day can increase the risk of developing liver cancer. Alcohol is involved in the diagnosis of between 25-30% of all liver cancer cases in the U.S.

Liver Cirrhosis: Individuals with cirrhosis of the liver are at higher risk of developing hepatocellular carcinoma - the most common liver cancer type. Cirrhosis is a liver condition caused by liver damage, in which the healthy tissue of a liver is overtime replaced by scar tissue. The scar tissue can block off blood flow that passes through the liver, interfering with healthy liver function.

This condition can be caused by an infection with the hepatitis B or C virus, long-term alcohol abuse, or liver damage caused by metabolic disorders.

When cirrhosis is developed, the rate of development of primary liver cancer (HCC) is estimated to be around 3-5% per year.

Infection with Hepatitis B or C Virus: Even if cirrhosis of the liver does not occur as a result of the infection, a chronic infection with the hepatitis B, hepatitis C, or both viruses can increase the risk of developing liver cancer.

Hepatitis B can be passed between people through select bodily fluids, such as blood or semen. While the virus is contained in saliva, it is not believed to spread through kissing or sharing of utensils.

Hepatitis C can be transmitted only through contact with infected blood.

Obesity: One of the most serious and preventable causes of liver cancer is obesity. This complex disease is associated with metabolic syndrome, as well as non-alcoholic fatty liver disease.

Up to 30% of adults in the U.S. have fatty liver disease, which can progress into Non-Alcoholic Steatohepatitis (NASH) - a disease that is involved in upto a third of all liver cancer cases 7.

In addition, the incidence of NASH-related cases of liver cancer is increasing, and patients affected by NASH may encounter worse outcomes, including in other types of cancers.

Type 2 Diabetes: People with type 2 diabetes are about two to three times more likely to develop primary liver cancer when compared to those without diabetes 8.

This increase in risk may be due to type 2 diabetes patients often also being obese or overweight, which can negatively affect the liver.

Aflatoxins: This substance is a poisonous carcinogen and mutagen that is produced by a fungus that pollutes wheat, corn, rice, soybeans, and certain types of nuts. The contamination typically occurs because crops and foods are stored in moist, warm environments, and more frequently occurs in warmer climates.

Exposure to aflatoxins long-term is a major risk factor for liver cancer, and is especially serious in people with Hepatitis B or C infections. The U.S. federal government mitigates some of this risk by regularly testing the content of aflatoxins in foods and produce.

Liver Cancer Diagnosis

While some liver cancers can be found by testing people that are at higher risk with no symptoms (known as screening), the majority of liver cancers are discovered because they are causing symptoms.

In case that you are experiencing any of the symptoms and signs of liver cancer, it is suggested that you visit your doctor, who will be able to examine your medical history, perform a physical exam, and order tests that would be used to confirm if a cancer is present.

Tests and examinations to diagnose liver cancer include a variety of imaging tests, biopsies, and lab tests.

Imaging Tests

Imaging tests include the use of x-rays, soundwaves and magnetic fields to produce images of the body on the inside.

Common Imaging Tests for Liver Cancer Include:

Computer Tomography - Commonly known as the CT scan, this is a powerful x-ray test that creates highly detailed images of the body. Doctors may order a CT scan of the abdomen to help find different types of tumors within the liver.

This test can provide specific knowledge about the shape, size, and location of any tumors within the liver (or in other places of the abdomen), and is a test that can with high certainty confirm the diagnosis.

Additionally, CT scans can be used to lead a biopsy needle into a suspected tumor (otherwise known as a CT-guided needle biopsy).

Magnetic Resonance Imaging (MRI) - Similarly to computed tomography scans, MRI scans produce highly detailed images of soft tissues within the body. However, instead of x-rays, this technology uses strong magnets and radio waves.

In certain instances, MRI scans can give information about a tumor being benign or malignant.

Biopsy

A biopsy is a procedure in which a sample of a tissue is removed from the body for further examination. In cases when imaging tests are unable to accurately determine if a tumor is malignant or benign, a doctor may order a biopsy.

A major issue with this procedure for doctors is that a biopsy may disturb the tumor and help the cancer spread to tissues that become damaged as a result of the procedure.

This becomes a significant concern, as the best course of action for some liver cancer patients may be surgery or a liver transplant, and a spread of the cancer into other parts of the body may make these patients ineligible for the procedure.

A biopsy can be performed in several ways:

Laparoscopic Biopsy - Laparoscopy (also known as diagnostic laparoscopy) is a surgical procedure used to observe and examine internal organs inside the abdomen. A biopsy specimen can be extracted during a laparoscopic procedure.

Surgical Biopsy - If other types of biopsy results were not conclusive, or if cells in question cannot be accessed with other biopsy procedures, the doctor may suggest a surgical biopsy.

During this procedure an incision is made into the skin to access the area of cells that is under suspicion. Prior to the surgical biopsy, the patient may receive local anesthetics to numb the biopsy area, and in certain biopsy procedures general anesthetics may be required.

Needle Biopsy - During a needle biopsy, a hollow needle is inserted into the abdomen, and then into the liver. Prior to the needle being placed, the biopsy area is first numbed with a local anesthetic.

The doctor will use the help of imaging technologies, such as an ultrasound or a CT scan to guide the needle.

Lab Tests

Prior and after the diagnosis, there are several reasons why your doctor may order lab tests:

  • To help in determining a diagnosis
  • To help uncover the likely cause of the liver cancer
  • To get an understanding of how well other organs are working and the level of your general health
  • To determine how well the liver is working, as this information is used for determining treatments
  • To see if the chosen treatment course is working well

Alpha-Fetoprotein (AFP) Blood Test - This protein is found in higher levels in people with liver cancer, liver disease, other cancers, or women who are pregnant.

In early stage liver cancer, this test may not yield useful results, as the AFP levels are typically within the normal range at that stage. However, this test can be useful for people that have already been diagnosed with liver cancer, as decreasing levels of AFP may be one of the signs that a treatment is effective.

Liver Function Tests - Since liver cancers primarily affect patients with already damaged livers from diseases like cirrhosis or hepatitis, it is important to determine the condition of the liver prior to treatment.

Viral Hepatitis Test - For patients that do not have a medical record of hepatitis B or C, the doctor may order blood tests to check for this virus.

Treatments

There isn’t a single liver cancer treatment that is suitable for every patient. After a diagnosis has been determined, your doctor will create a personalized treatment plan, which will be based on specific information about you and the cancer.

When evaluating different courses of treatments, healthcare providers will take in to account:

  • The overall health of a patient
  • The stage of the liver cancer
  • Functionality and health of the liver
  • In patients with cirrhosis, the amount and severity of scarring
  • If the cancer can be removed entirely by surgery

Common treatments for liver cancer include:

Surgery

Depending on the condition of the liver and stage of liver cancer, patients may receive one of the following types of surgery:

Liver resection - Also known as partial hepatectomy, this is a surgery to remove the tumor from the liver. It is used as primary treatment for patients with good liver function and a single tumor that has not spread into blood vessels.

Liver transplant - A liver transplant is the main treatment procedure in patients with severe cirrhosis. Livers that have severe damage from this disease are likely to not function well after a surgical removal of the tumour, and therefore liver resection is often not an option for these patients.

Transarterial Chemoembolization (TACE)

TACE is a procedure used to shrink and control tumors in the liver. It works by delivering chemotherapy directly into the tumor, while also blocking off its blood supply.

This treatment is offered to patients when surgical removal of the tumor isn’t an option, and the cancer hasn’t yet spread to major blood vessels in the liver or to other parts in the body.

Ablation Therapy

Ablation is a treatment that destroys cancerous cells in the liver without physically removing the tumor. This treatment option is offered to patients that aren’t eligible for surgery.

Percutaneous Ethanol Injection (PEI) - This treatment involves an injection of a concentrated ethanol alcohol solution directly into the tumor. This procedure works best on smaller tumors that are less than or equal to 3cm (1.18in) in size.

PEI typically takes 4-6 sessions to complete the ablation, and the needle insertion is guided with an ultrasound.

Radiofrequency Ablation (RFA) - Also known as rhizotomy, this is a non-surgical and minimally invasive procedure used to treat liver cancer. It is the most common ablation treatment for cancer.

It involves a guided insertion of a needle with an electrode through the abdomen and into the tumor. High-frequency electrical currents are then passed through the electrode, creating a small area of heat that destroys the cancer cells.

RFA is most effective for liver tumors that are 2.5cm (0.98in) or less in size, and when there are three or less tumors overall.

Quick Facts About Liver Cancer

  • An estimated 42,810 adults in the U.S. (12,640 women and 30,170 men) will be diagnosed with primary liver cancer in 2020 9
  • An estimated 30,160 deaths will occur (10,140 women and 20,020 men)
  • Incidence of liver cancer has tripled since 1980
  • In comparison to the U.S., liver cancer is a lot more common in Southeast Asia and sub-Saharan Africa
  • The 5-year survival rate for liver cancer is 18%, compared to only 3% 40 years ago

Current Liver Cancer Clinical Trials

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2 "Epidemiology and risk factors: intrahepatic cholangiocarcinoma." 2 Jan. 2017, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5411279/.

3 "Cancer, Liver Angiosarcoma - StatPearls - NCBI Bookshelf." 25 Jun. 2020, https://www.ncbi.nlm.nih.gov/books/NBK538224/.

4 "BCLC staging system and the Child-Pugh system | Liver ...." https://www.cancerresearchuk.org/about-cancer/liver-cancer/stages/bclc-staging-system-child-pugh-system.

5 "Liver Cancer Causes & Factors That Put You at Risk | CTCA." https://www.cancercenter.com/cancer-types/liver-cancer/risk-factors.

6 "Liver Cancer: Statistics | Cancer.Net." https://www.cancer.net/cancer-types/liver-cancer/statistics.

7 "Non-Alcoholic Fatty Liver Disease | Michigan Medicine." https://www.uofmhealth.org/conditions-treatments/digestive-and-liver-health/fatty-liver-disease-non-alcoholic.

8 "Liver Cancer and Diabetes - Diabetes UK." 15 Jan. 2019, https://www.diabetes.co.uk/diabetes-complications/liver-cancer.html.

9 "Liver Cancer: Statistics | Cancer.Net." https://www.cancer.net/cancer-types/liver-cancer/statistics.