Hepatocellular Carcinoma

Hepatocellular carcinoma is the most common type of liver cancer, affecting thousands of people each year. While it is a serious condition that often develops in people with long-term liver damage, early detection and advances in treatment offer important opportunities for improving outcomes.

Table of contents

• What is hepatocellular carcinoma?
• Affected organ
• How common is HCC?
• Symptoms of hepatocellular carcinoma
• Causes and risk factors
• How is HCC diagnosed?
• Treatment options
• Outlook and survival
• Who should be screened?

What is hepatocellular carcinoma?

Hepatocellular carcinoma, often called HCC, is a type of cancer that starts as a growth of cells in the liver. It is the most common form of liver cancer, accounting for about 85% to 90% of all primary liver cancers (cancers that begin in the liver, rather than spreading there from another part of the body)^[1][2].

HCC starts in liver cells called hepatocytes, which are the main type of cells that make up the liver^[1]. The disease happens when something causes changes in these cells, making them grow out of control and form a growth called a tumor^[1].

Hepatocellular carcinoma is considered an aggressive, or fast-growing, cancer^[2]. In the beginning, it grows slowly, but most people don’t learn they have it until it’s advanced and spreading more quickly^[2]. The tumor can damage healthy liver tissue and grow into nearby blood vessels. Cancer cells can break away and spread to other parts of the body^[1].

• Liver

Affected organ

The liver is an organ that sits just under the rib cage on the right side of the belly. It performs many important tasks for the body^[1]. A healthy liver breaks down nutrients that your body needs, helps your body get rid of toxins, and supports healthy blood flow^[4].

HCC can prevent the liver from doing these vital functions. Eventually, it can cause liver failure^[4].

How common is HCC?

Hepatocellular carcinoma is a significant global health challenge. It is now the sixth most common type of cancer diagnosis and the third leading cause of cancer-related deaths worldwide^[2]. Liver cancer is the seventh most common cause of cancer death in Australia^[7].

An estimated 41,000 people in the United States were diagnosed with liver cancer in 2022, with 75% to 80% of these cancers being HCC^[4]. The disease accounts for more than 90% of primary liver tumors^[3].

HCC is two to three times more common in men than in women. Most people diagnosed are 60 years or older^[2]. The disease has become much more common over the last 40 years, with rates continuing to increase^[7].

HCC is one of the fastest growing cancers in the United States and one of the few with a five-year survival rate of less than 20%^[3]. Despite improvements in treatment, because it is often diagnosed late, only one in five people diagnosed with HCC will survive more than five years^[7].

Symptoms of hepatocellular carcinoma

One of the most challenging aspects of HCC is that it may not cause symptoms right away, which means it can grow without being detected^[1]. Like other liver cancers, HCC doesn’t usually cause any symptoms in the early stages. When symptoms do eventually appear, it usually means the cancer is in an advanced stage^[7].

As HCC progresses, you may notice the following symptoms^[2][7]:

• Fullness or a knot under your ribs on your right side (symptoms of an enlarged liver)
• Fullness under your ribs on your left side (symptoms of an enlarged spleen)
• Eyes and skin turning yellow (signs of jaundice)
• A stomach that feels swollen, like it’s filling up with fluid
• Loss of appetite or feeling full after a small meal
• Unexplained weight loss
• Nausea and vomiting
• Itching
• Pain in the upper right of the trunk or in the right shoulder
• Feeling tired and weak
• Pale stools (bowel movements)
• Dark urine

Many conditions cause similar symptoms, and most aren’t as serious as hepatocellular cancer. If symptoms last longer than two weeks, it’s best to see a healthcare provider^[2].

Causes and risk factors

Most people diagnosed with HCC have cirrhosis of the liver (approximately 80%), although some have a condition that can lead to cirrhosis. In some instances, the condition never progresses to cirrhosis, but people still develop HCC^[2]. Cirrhosis is severe scarring of the liver caused by long-term damage.

Hepatocellular carcinoma happens most often in people with chronic liver conditions^[1]. HCC occurs in 85% of patients diagnosed with cirrhosis, and the annual incidence of HCC in patients with cirrhosis is 2% to 4%^[3].

With these conditions, unmanaged long-term liver inflammation can lead to severe scarring and, eventually, HCC^[2].

Conditions that increase your risk of HCC include^[2][3]:

• Hepatitis B infection: A viral infection that spreads through bodily fluids. Hepatitis B affects more than 250 million individuals worldwide and is the most common cause of chronic hepatitis worldwide. Hepatitis B virus infection can lead to HCC even without liver cirrhosis or before cirrhosis occurs. The hepatitis B virus and hepatitis C virus infection account for 56% and 20% of HCC cases diagnosed worldwide, respectively.
• Hepatitis C infection: A viral infection that spreads through blood. Chronic hepatitis B virus and chronic hepatitis C virus are associated with more than 70% of cases of hepatocellular carcinoma.
• Metabolic dysfunction-associated steatotic liver disease (MASLD): A condition that causes excess fat to build up in your liver. You’re more likely to have MASLD if you have obesity, an inherited metabolic syndrome, or Type 2 diabetes. MASLD is becoming a more frequent risk factor in Western countries.
• Alcohol use disorder: Alcohol is difficult for your liver to process. Drinking too much of it can eventually lead to cirrhosis and liver cancer.

If you belong to a high-risk group, your healthcare provider may suggest regular screenings to catch HCC early, when it’s treatable. They can also help you take steps to reduce risk factors, like helping you quit smoking or drinking^[2].

How is HCC diagnosed?

Liver ultrasound is the main way doctors find HCC. If you have problems with your liver, you are likely to have regular ultrasounds to check for HCC^[7]. Sometimes your doctor will combine the ultrasound with a blood test to look for levels of alpha-fetoprotein (AFP), a protein that is produced by HCC tumors. However, AFP levels can be normal even if you have HCC^[7].

A diagnosis of HCC can’t be made from an ultrasound alone. If an abnormal lump is found, your doctor will then order a CT scan (computed tomography) or an MRI scan (magnetic resonance imaging) to make a diagnosis of HCC^[7]. Liver cancer is one of the cancers where a biopsy may not be needed to make decisions about your care. Sometimes, liver cancer can be reliably diagnosed on imaging studies such as CT scans or MRIs^[21].

Sometimes, it’s necessary to look at a small sample of liver tissue taken in a biopsy to confirm the cancer^[7].

Once HCC is confirmed, you may need further tests to work out the stage of the cancer, meaning how far it has spread^[7].

Treatment options

Management of hepatocellular carcinoma is best performed in a multidisciplinary setting. Patients should be cooperatively managed by hepatologists (liver doctors), transplant and liver surgeons, medical cancer specialists, interventional radiologists, and palliative care specialists^[12].

Treatment often depends on how advanced the cancer is and how well the liver is working^[1]. Treatment options depend on the size, number, and location of tumors; presence or absence of cirrhosis; operative risk based on extent of cirrhosis and other diseases; overall performance status; whether the portal vein is open; and presence or absence of disease that has spread to other parts of the body^[12].

The main treatment options include^[1][2][12]:

• Surgery to remove the cancer: A partial removal of the liver (surgery to remove the part of the liver where cancer is found) may be done. A wedge of tissue, an entire section, or a larger part of the liver, along with some healthy tissue around it, is removed. The remaining liver tissue takes over the functions of the liver and may regrow.
• Liver transplant: In a liver transplant, the entire liver is removed and replaced with a healthy donated liver. A liver transplant may be done when the disease is in the liver only and a donated liver can be found. Although it can be life-threatening, catching HCC early can mean successful treatment with surgery or a liver transplant.
• Ablation therapy: Ablation therapy removes or destroys tissue. Different types include radiofrequency ablation (using high-energy radio waves to heat and kill cancer cells), microwave therapy, alcohol injection into the tumor, and cryoablation (freezing cancer cells).
• Embolization therapy: This treatment is used for people who cannot have surgery to remove the tumor or ablation therapy and whose tumor has not spread outside the liver. It uses substances to block or decrease the flow of blood through the main artery to the tumor. When the tumor does not get the oxygen and nutrients it needs, it will not continue to grow.
• Radiation therapy: This treatment uses high-energy rays to kill cancer cells.
• Immunotherapy: These are medicines that work with your immune system to fight cancer.
• Targeted therapy: These are drugs that target specific features of cancer cells. Six systemic therapies have been approved based on major trials: atezolizumab plus bevacizumab, sorafenib, lenvatinib, regorafenib, cabozantinib, and ramucirumab.

Other treatments may ease your symptoms and help you live longer^[2].

Outlook and survival

Hepatocellular carcinoma is one of the most serious cancers^[1]. The five-year survival of HCC is 18%, second only to pancreatic cancer^[3]. The low survival rate is primarily driven by diagnosis at a late stage, where the median survival is one to three years compared to 10 years in early-stage HCC^[14].

More than half of all people with HCC are diagnosed in an advanced stage^[4]. Eventually, HCC can lead to liver failure. At this point, HCC is challenging for healthcare providers to treat^[2].

The earlier you find out you have HCC, the better the chance of having a treatment that can cure it^[7]. Surgery to remove the tumor or a liver transplant can treat HCC in its early stages. Only about 5% of hepatocellular carcinoma patients are suitable for transplantation; these patients may have a five-year survival of greater than 75% with tumor recurrence rates as low as 15% at five years^[12].

HCC also tends to happen in people with serious liver disease, which may make treatment more difficult^[1]. The coexisting problem of cirrhosis and liver dysfunction leads to poor outlook^[3].

Who should be screened?

Given how serious HCC is, you should receive regular checks for signs of HCC if you have cirrhosis or MASLD^[2]. Some people are more at risk of developing HCC, and regular screening is important for early detection.

It’s recommended that you have an ultrasound and possibly a blood test to check for HCC every six months if^[7]:

• You have cirrhosis or have ever been diagnosed with cirrhosis
• You have long-standing hepatitis B infection and:
  • You are a man of Asian heritage over 40 years or a woman of Asian heritage over 50 years
  • You are of African heritage and aged over 20 years
  • You are of Aboriginal and Torres Strait Islander heritage and aged 50 years
  • You have a family history of liver cancer

If you’re at high risk for HCC, you should see your healthcare provider regularly to check for signs of HCC^[2].