Liver Cancer

Liver cancer is a disease of the liver, one of the largest organs in the body that performs many important functions in the body. Located under the diaphragm in the right upper abdominal cavity, the liver manufactures various essential proteins, processes and stores nutrients and destroys toxins and poisons.

Cancer in the liver occurs when mutations cause cells to mutate and multiply uncontrollably. This can be due to mutations in the genes of cells. Mutations in the liver can be caused by chronic inflammation due to viruses (hepatitis B and C), toxins (alcohol, alfa-toxins) and metabolic injuries (non-alcoholic fatty liver disease (NAFLD), steatohepatitis (NASH)). 

When cells grow and divide out of control, extra tissue is formed creating a mass or lump called a tumour. Tumours can be benign or malignant. Benign tumours are not cancers as they grow slowly and do not spread to other parts of the body. Malignant tumours are cancerous growths which have the potential to spread to other parts of the body. 

What are the types of liver cancer? 

There are two main types of liver cancer:

• Primary liver cancer or hepatocellular carcinoma (HCC) originates in the liver. HCC is one of the most common cancers in Singapore, and it more commonly occurs in those aged above 50 years of age. Liver cancer is mainly an Asian disease, and is prevalent in South-East Asia, China, Japan and Korea.
• Metastatic or secondary liver cancer occurs when cancer that originates elsewhere in the body spreads to the liver. The most common type of metastatic liver tumours is caused by colon cancer that has spread to the liver. 

Note: The information here on will focus on HCC, which is the most common type of primary liver cancer.

What are the symptoms of liver cancer?

In most patients with HCC, the most common type of primary liver cancer, there are often no symptoms even when the tumour has grown large. As the cancer advances, some symptoms may show. These include:

• Pain in the upper abdomen can result, especially in the upper right part of the abdomen and can sometimes be felt in the back and rib cage area.
• General weakness and lethargy which can be a result of liver cancer impacting hormone levels in the body.
• Loss of appetite or feeling very full after a small meal can occur as the cancer spreads.
• Nausea or vomiting can result as the cancer spread, creating discomfort in the digestive tract.
• Abdominal swelling or a bloated abdomen can occur as the cancer causes the liver to get bigger and results in abdominal swelling. It can also increase pressure in the liver resulting in ascites or fluid accumulation in the abdominal cavity, which in turn causes abdominal swelling.
• Jaundice, which symptoms include the yellowing of the skin and eyes and dark coloured urine, can occur when cancer causes the liver or bile duct to function improperly, causing bilirubin to build up in the blood.
• Changes in the stool consistency so it becomes white or chalky as liver cancer causes the loss of bile.
• An enlarged spleen can result if the cancer causes the pressure in blood vessels running to the spleen to build up.
• Enlarged veins on the belly, visible through the skin, can occur if the cancer causes increased pressure in the liver, causing blood to back up or collect in the veins. 

When should you see a doctor?

Make an appointment with your doctor if you experience any signs or symptoms that worry you.

How is liver cancer prevented?

• Take measures to reduce the risk of hepatitis B and hepatitis C
  You can reduce your risk of hepatitis B by receiving the hepatitis B vaccine. Vaccines for hepatitis B are available for children and adults. Children should get hepatitis B immunisation at birth as part of the Singapore National Childhood Immunisation Schedule. There is currently no vaccine for hepatitis C. 
  
  Family members of patients with hepatitis B are advised to check their own hepatitis B status. If you are at risk for hepatitis B or C infection, consider undergoing a screening test. 
  
  Those with chronic hepatitis B or C should also visit their doctors for regular surveillance with imaging tests, such as ultrasound. If you have chronic hepatitis B or C, you might be a candidate for antiviral therapy, which can slow down the progression of liver disease and may decrease, but not totally eliminate the risk of liver cancer. 
  
  
• Adopt a healthy lifestyle
  You can lower your risk of developing liver cancer by leading a healthy lifestyle - exercise regularly, control your weight and eat a healthy balanced diet. 
  
  Chronic alcohol use is a risk factor and can lead to liver cirrhosis, which increases the risk of liver cancer. The Health Promotion Board recommends no more than two standard drinks a day for men, and no more than one standard drink a day for women. 
  
  
• Liver cancer screening
  Screening is advised for high-risk individuals with liver cirrhosis or chronic hepatitis B infection. Regular screening may involve blood tests for alpha-fetoprotein (AFP), liver function assessments, as well as ultrasound scans of the liver every 6 months.

What causes liver cancer?

HCC, the most common type of primary liver cancer, develops due to several cellular processes. One major cause is genetic mutations in liver cells, which may occur naturally or be induced by environmental exposure. These mutations interfere with normal cell regulation and lead to abnormal growth and tumour formation.

Chronic inflammation in the liver caused by long-standing conditions such as cirrhosis or exposure to carcinogens, can also damage cellular DNA and accelerate the development of HCC. Prolonged contact with harmful substances like industrial chemicals, can also lead to significant cellular damage that may cause liver cancer.

What are the risk factors for liver cancer?

People with risk factors are more likely to develop primary liver cancer or HCC. The more risk factors a person has, the greater the chance that liver cancer will develop. However, many people with known risk factors do not develop the disease.

If you think you may be at risk for liver cancer, discuss it with your doctor to see how to manage your risk.

Factors that may increase the risk of primary liver cancer:

• Chronic infection with hepatitis B or C: 
  • Hepatitis B is the most common cause of primary liver cancer. Hepatitis B can be transmitted from an infected mother to her baby during pregnancy. In the adult setting, hepatitis B and C can be transmitted by contact with infected body fluids, for example saliva, blood, sperm and other secretions. Infection of liver cells with hepatitis B viruses causes DNA damage, which can lead to liver cirrhosis (hardening of the liver). 
  • Hepatitis C causes primary liver cancer by damaging the liver through chronic inflammation, which can also lead to liver cirrhosis. 
  • An individual with hepatitis B or C is 100 times more likely to get liver cancer compared to an individual without hepatitis B or C. 
• Excessive alcohol consumption - repeated and excessive alcohol abuse can lead to liver cirrhosis and liver cancer. 
• Non-alcoholic fatty liver disease (NAFLD) - Almost half the adult population in Singapore may have NAFLD. This can progress to non-alcoholic steatohepatitis (NASH), liver cirrhosis and primary liver cancer. NAFLD and NASH are increasingly important causes of HCC in Singapore and globally. NAFLD is related to diabetes mellitus and obesity. However, many patients with NAFLD are not obese. 
• Cirrhosis or hardening of the liver - People with liver cirrhosis, an irreversible condition in which healthy liver cells are replaced by scar tissue, are at greater risk for developing liver cancer and should undergo regular screening. Cirrhosis happens because of liver damage from a variety of causes, but the most common causes are hepatitis B or C infections, fatty liver and excessive alcohol consumption. 
• Exposure to poison (aflatoxins) - Aflatoxins are harmful food contaminants made by certain moulds that grow on poorly stored grains and nuts. 
• Inherited metabolic diseases that affect the liver - such as haemochromatosis, which causes excess deposits of iron in the body, puts a person at a higher chance of developing primary liver cancer. 

What are some complications that arise from liver cancer?

Liver cancer can cause complications and other diseases, as the cancer spreads and affects nearby organs such as:

• Bile duct obstruction
  Liver cancer can obstruct the ducts that carry bile from the liver to the small intestine. Without bile, proper digestion is impaired and symptoms such as pain in the abdomen, itching, nausea, vomiting and jaundice can occur.
• Bleeding and anaemia
  Liver cancer can cause the liver to malfunction and not produce enough proteins to facilitate blood clotting, resulting in excessive bleeding or anaemia. 
• Portal hypertension
  Liver cancer can block blood flow through the liver, causing increased pressure in the portal vein that transports blood from the digestive organs to the liver. This can cause gastrointestinal bleeding, brain function decline, and adversely impact platelet and blood cell count. 
• Hypercalcaemia
  Liver cancer can cause high calcium levels in the blood which is known as hypercalcaemia. Symptoms are nausea and vomiting, muscle weakness, and confusion, which can become life-threatening without treatment. 
• Hepatorenal syndrome
  Liver cancer and disease can sometimes lead to kidney disease. Sometimes this results in changes in blood vessels that reduces blood flow to the kidneys and causes hepatorenal syndrome. 
• Hepatic encephalopathy
  Hepatic encephalopathy is a decline in brain function that can result from advanced liver disease, when the liver can no longer eliminate toxins from the blood causing a build-up in the bloodstream and damaging the brain.

How is liver cancer diagnosed?

There are a number of ways to screen and diagnose liver cancer such as:

• Imaging using ultrasound
  The simplest imaging study of the liver is an ultrasound. There is no radiation risk, and it can be done on a regular basis, especially in individuals who are at risk of liver cancer, for e.g., hepatitis B carriers. However, it is not the most accurate or specific imaging study. 
  
  
• CT or MRI scan
  The current gold standard for diagnosing primary liver cancer being multi-phasic imaging with CT scans or MRI scans. A CT scan is a better way of detecting liver cancer and is crucial for treatment planning. This is the basic imaging done by the liver surgeon to detect and plan a treatment strategy. In certain cases, if a CT scan is not enough or is inconclusive, additional investigations like MRI or a PET scan may be performed. 
  
  
• Blood tests
  A blood test can be done to measure the level of a protein produced by the liver called alpha fetoprotein (AFP). AFP is associated with primary liver cancer. However, this blood test should not be used in isolation or as a routine screening test. 
  
  
• Liver biopsy
  A liver biopsy involves the removal of a small amount of liver tissue via a needle procedure for laboratory testing. For primary liver cancer, a biopsy is not usually necessary or advised as it carries a potential risk of bleeding and spreading the tumour. A biopsy is only advised by the doctor if there is uncertainty in diagnosis, based on other methods. 
  
  
• Screening for high-risk patients
  In high-risk patients, regular screening is carried out using abdominal ultrasound and a blood test for serum alpha-feto protein (AFP), which is a cancer marker. If either the ultrasound or serum AFP is abnormal, then a CT scan or MRI scan would be done to confirm the diagnosis. 

What are the stages of liver cancer?

The most commonly used staging system for HCC is the Barcelona Clinic Liver Cancer system (BCLC), which takes into account liver function, tumour size and symptoms.

Stage 1 HCC – There is a single tumour in the liver less than 2 centimetres in size, bilirubin level is normal.

Stage 2 HCC – There is a single tumour in liver less than 5 centimetres in size, or there is more than one tumour less than 3 centimetres in size. There may be spread to the blood vessels.

Stage 3 HCC – There is more than one tumour and, or a tumour larger than 5 centimetres. Cancer may have spread to another organ, large blood vessels and lymph nodes.

Stage 4 HCC – The cancer has metastasized or spread to areas further away in the body such as the lungs, bones and lymph nodes.

How is liver cancer treated?

While HCC is the third and fourth-most cause of cancer-related death in Singapore for men and women, respectively, early-stage liver cancers are responsive to treatment with either surgery or ablation techniques. The chance of survival for individuals with early-stage liver cancers beyond 5 years is more than 40%.

Treatment for primary liver cancer should be individualised to each patient and depends on:

• Stage of the cancer 
• Underlying liver function of the patient 
• General health and fitness of the patient 
• Availability of specialised treatment 
• An individual with cancer should be assessed by a specialist to determine which modality of treatment is best suited for them. 

Surgery

Surgery offers the best chance for cure and long-term survival for primary liver cancer. It can be in the form of resection, where the part of the liver with the cancer is removed, or a liver transplant. Unlike many other organs where complete removal of the organ (such as both breasts, the entire colon or stomach) is possible, a person cannot live without a liver.

Resection is undertaken when complete removal of the cancer is feasible and yet leaves enough liver intact for the patient’s needs.

In addition to traditional open surgery and liver transplantation, newer surgical techniques and minimally-invasive technologies have emerged, offering improved precision and reduced recovery times.

The vast majority of liver resections at Singapore General Hospital and the National Cancer Centre Singapore can now be performed by minimally-invasive surgery (MIS - which is also referred to as laparoscopic or keyhole surgery) regardless of tumour size, location, previous surgery and type or extent of resection. This is due to the Department of Hepato-Pancreato-Biliary/Transplant Surgery’s vast experience in minimally invasive liver. Presently, the Department of Hepato-Pancreato-Biliary/Transplant Surgery is one of the highest volume centres for MIS liver resections in the region, performing over 150 MIS liver resections per year.

Liver transplant

In cases where there are multiple cancer nodules, the cancer is recurrent or the underlying liver disease is advanced, a liver transplant may be recommended. A donor liver can be from a cadaveric donor or from a healthy individual who is willing to donate part of their liver (i.e. a living donor). If a liver transplant is recommended, a series of tests and medical assessments will be carried out to assess if the patient is fit to undergo a liver transplant. Following a liver transplant, the patient will need to take immunosuppression drugs for life to prevent organ rejection.

A living liver donation, in which a healthy person donates a portion of their liver to someone with liver failure, is a very safe procedure that can mostly be performed via MIS. Singapore General Hospital and the National Cancer Centre Singapore is one of the leading centres in the region which consistently performs adult living donor hepatectomies procedures using a minimally-invasive approach.

Localised chemotherapy and radiotherapy

Localised chemotherapy and radiotherapy treatments are done when surgery is not possible. Localised chemotherapy involves delivery of chemotherapy directly to the liver cancer via a tube inserted at the groin. This has the advantage of delivering a higher dose of chemotherapy to the cancer, while minimising side effects to the rest of the body.

Localised radiotherapy with yttrium 90, is similar to localised chemotherapy. It involves delivering radioactive materials directly to the liver cancer via a tube inserted at the groin. A series of tests is performed before administering this form of treatment to determine if a patient is suitable.

Ablation techniques

Ablation techniques are suitable for small cancers measuring less than 3cm in size. The efficacy of ablation in small cancers is close to that achieved with surgery. The most common form of ablation technique is Radiofrequency Ablation (RFA). This involves inserting a thin rod through the liver into the cancer and using radiofrequency to generate heat, which kills the cancer cells.

Microwave is another source of energy used for ablation. Access of the rod to the cancer can be via the skin and is guided by ultrasound or CT scan. In this situation, general anaesthesia may not be necessary. General anaesthesia is required if access of the rod is directly into the liver via open or laparoscopic (keyhole) surgery.

Systemic treatment

Systemic treatment is undertaken in advanced cases where other treatment options are not suitable. Sorafenib, which is taken daily as an oral medication, is the most commonly prescribed systemic treatment. Intravenous chemotherapy may be given in selected cases.

Clinical trials

In advanced cancer cases where all the above treatment options are not suitable, participation in a suitable clinical trial may be suggested. Clinical trials aim to determine if new treatment medication is effective in controlling the disease.

Palliative care

When treatment is not possible or is ineffective, palliative care can help to ease symptoms such as pain, ascites (collection of fluid in the peritoneal cavity that can cause breathlessness and discomfort) and jaundice (which causes the skin to turn yellow and feel itchy).

Palliative care, also increasingly known as supportive care, is a holistic approach to caring for anyone diagnosed with a serious illness such as cancer, to allow them to live as well as they can, for as long as they can. Palliative and supportive care is specialised support provided by a multi-disciplinary team of doctors, nurses, clinical psychologists, medical social workers and other allied health professionals to help patients.

Before surgery, your surgeon will perform comprehensive medical assessments including blood tests and scans to see if you are suitable for surgery and advise on the risks involved. Your treatment recommendation is often based on consensus by a group of medical specialists' opinions (the tumour board), who come together to discuss the benefits and limitations of every treatment strategy.

Before surgery, the anaesthesia team will assess your fitness for surgery and advise you on various aspects of general anaesthesia and pain control after surgery. Specialist nurses will also provide pre-surgery counselling so that you know what to expect.

After surgery, you will be given regular outpatient appointments to see your team of doctors. During these appointments you may have blood test and scans to check if the cancer recurs.

It is important to follow your doctor's advice, keep to your clinic visits and do the recommended scans and tests, so that timely treatment can be administered if the cancer recurs, or other problems occur.

1. What is the survival rate for liver cancer?
   The survival rate for liver cancer depends on the stage at which it is diagnosed. If detected early, when the tumour is small and treatment can be effectively administered, the five-year survival rate can be more than 40%. When liver cancer is diagnosed at an advanced stage, the survival rate significantly decreases as treatment options become more limited. 
   
   
2. Can liver cancer be cured?
   If diagnosed at an early stage, liver cancer may be cured with surgical options such as a liver resection. For liver cancer diagnosed at an advanced stage, treatment is focused on controlling the cancer, slowing its progression and managing symptoms rather than curing the disease. 
   
   
3. What are the early symptoms of liver cancer?
   Liver cancer often does not cause symptoms in its early stages. When symptoms do appear, they may include unexplained weight loss, a loss of appetite, nausea, a feeling of fullness after eating small amounts and pain or swelling in the abdomen. If any of these symptoms occur, it is important to see a doctor for further evaluation. 
   
   
4. What is the life expectancy of liver cancer?
   The life expectancy for liver cancer varies significantly depending on the stage at diagnosis and the patient's overall health. Early-stage liver cancer has a relatively better prognosis, with many patients achieving a five-year survival rate exceeding 40% when treated with surgery or ablation techniques. For advanced-stage liver cancer, life expectancy is usually shorter, often ranging from several months to a few years, as the cancer is more challenging to treat and may have spread to other parts of the body. 
   
   
5. How aggressive is liver cancer?
   Liver cancer, especially hepatocellular carcinoma (HCC), can be aggressive, as it often grows and spreads quickly if not detected early. Its aggressiveness is influenced by underlying conditions such as cirrhosis or chronic hepatitis, which can compromise liver function and hence affect treatment options. Early detection through regular screening in high-risk individuals is crucial for improving outcomes. 
   
   
6. What are the symptoms of stage 4 liver cancer?
   In stage 4 liver cancer, symptoms are more pronounced and may include severe abdominal pain, significant weight loss, persistent fatigue, and jaundice (yellowing of the skin and eyes). Additional symptoms may include swelling in the abdomen due to ascites, visible veins on the abdomen, and confusion or cognitive decline caused by hepatic encephalopathy. These symptoms are often accompanied by signs of cancer spread, such as bone pain or difficulty breathing. 
   
   
7. Does liver cancer spread quickly?
   Liver cancer has the potential to spread rapidly, particularly in individuals with compromised liver health or chronic conditions such as hepatitis or cirrhosis. Metastasis commonly occurs to nearby structures such as the lymph nodes, lungs, and bones. However, the rate of progression depends on the specific type of liver cancer, its genetic makeup, and the patient’s overall health. 
   
   
8. Does chemotherapy treatment work for liver cancer?
   Chemotherapy has limited effectiveness for primary liver cancer, as the liver’s ability to detoxify can reduce its impact. However, targeted therapies and immunotherapy, such as lenvatinib, bevacizumab and atezolizumab among others, have shown promise in treating advanced cases. Localized chemotherapy, like transarterial chemoembolization (TACE), can be more effective for patients with inoperable tumours, as it delivers the drugs directly to the tumour site, reducing systemic side effects.

SingHealth experts share more about liver cancer: