Liver Cancer (HCC, Hepatocellular carcinoma)

Liver cancer refers to malignant tumours that develop in the liver, most commonly from the liver’s primary cells called hepatocytes. In Singapore, it ranks as the fifth most common cancer, representing about 5.7% of new cases. The most common form of primary liver cancer is hepatocellular carcinoma (HCC), which arises from the main liver cells known as hepatocytes.

What is liver cancer?

Liver cancer refers to the uncontrolled growth of malignant cells either originating in the liver or spreading to it from other parts of the body. It is broadly classified into primary liver cancer, which starts in the liver, and secondary liver cancer, which arises from cancers elsewhere that metastasise to the liver.

• Primary liver cancer — this type begins within the liver itself. The most common form is hepatocellular carcinoma (HCC), which accounts for approximately 75–90% of all primary liver cancers. HCC is most often diagnosed in individuals with chronic liver disease, especially those with liver cirrhosis caused by long-term hepatitis B or C infection, alcohol-related liver damage, or non-alcoholic fatty liver disease.
• Secondary liver cancer — also known as metastatic liver cancer, this occurs when cancer cells spread to the liver from other organs. The most common sources include colorectal cancer, breast cancer, lung cancer, and neuroendocrine tumours.

Stages of Liver Cancer

Staging liver cancer involves assessing several factors, including tumour size, spread to lymph nodes or distant sites, liver function, and the patient’s overall health. One commonly used system for hepatocellular carcinoma (HCC) is the Barcelona Clinic Liver Cancer (BCLC) staging system, which guides treatment decisions by combining tumour burden with liver function and performance status.

• Stage 0 (Very early stage) — a single tumour less than 2 cm in size with no vascular invasion. Liver function is well preserved, and the patient has no symptoms.
• Stage A (Early stage) — a single tumour or up to three nodules smaller than 3 cm each. Liver function remains intact, and the patient’s physical status is good.
• Stage B (Intermediate stage) — multiple tumours present in the liver (multinodular), but liver function is still preserved. Patients are usually asymptomatic but not eligible for curative treatment.
• Stage C (Advanced stage) — cancer has invaded blood vessels (e.g., portal vein) or spread beyond the liver. Liver function may still be adequate, but patients often have cancer-related symptoms and a reduced performance status.
• Stage D (End stage) — this stage involves severely impaired liver function and poor general condition. The tumour may be of any size, but supportive care is the main focus due to limited treatment options.

Life Expectancy

Life expectancy and survival rates of liver cancer vary according to the stage of the disease, typically detection at early stages of the disease can improve the disease prognosis. The 5-year survival rates of liver cancer are typically as below:

• Localised tumour — 37%
  Metastasis to nearby sites — 13%
  Metastasis to distant sites — 3%

Survival rates may also vary according to the treatment you receive and how well your condition responds to them.

What are the symptoms of liver cancer?

Liver cancer often progresses silently, with few or no symptoms in its early stages. Most individuals only experience noticeable symptoms once the disease is more advanced. When present, symptoms may resemble those of liver cirrhosis and should not be ignored.

Common signs and symptoms of liver cancer include:

• A lump or fullness in the right upper abdomen (below the ribcage)
• Unexplained weight loss
• Jaundice (yellowing of the skin and eyes)
• Loss of appetite
• General discomfort or malaise
• Abdominal pain or swelling
• Nausea and vomiting
• Persistent fatigue or weakness
• Pale, chalky stools
• Dark-coloured urine

If you notice any of these symptoms, especially in the context of underlying liver conditions, consult a doctor promptly for further evaluation.

What causes liver cancer?

Liver cancer can be caused by several factors, including genetic factors, viral infections, cellular microenvironment, immune interactions, and chronic liver injury. Common sources of liver injury that can progress into liver cancer include:

• Viral hepatitis B and C infections — up to 70% of HCC are associated with chronic hepatitis B and C infections. These viruses typically cause injuries leading to liver cirrhosis, which can be the first step to progression towards liver cancer. In hepatitis B infections, sometimes liver cirrhosis may be absent.
• Non-alcoholic liver steatohepatitis and non-alcoholic fatty liver — excess fat stored in the liver is becoming a leading cause of HCC. Fatty liver disease can lead to HCC through various factors, including insulin resistance, obesity, diabetes, and inflammation of the liver. These factors can contribute to the development and progression of liver cancer.
• Alcohol — excessive alcohol intake can lead to liver cirrhosis by promoting inflammation, oxidative stress, and the release of endotoxins that damage liver cells over time.
• Aflatoxin exposure — Aflatoxins are toxic compounds produced by moulds such as Aspergillus flavus and Aspergillus parasiticus, which commonly contaminate improperly stored grains and food products. Long-term exposure to aflatoxins has been linked to growth impairment, liver cirrhosis, and an increased risk of developing hepatocellular carcinoma (HCC).

Who is at risk of liver cancer?

Most cases of liver cancer, particularly hepatocellular carcinoma (HCC), arise in individuals with underlying liver disease. 

• Chronic hepatitis B and C infections — Long-term infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) is one of the leading causes of liver cancer worldwide. These viruses cause persistent liver inflammation and damage, often progressing to cirrhosis, which is a major risk factor for HCC.
• Excessive alcohol consumption — heavy and prolonged alcohol intake can result in alcoholic liver disease, leading to cirrhosis. Chronic alcohol-related liver injury is a well-established contributor to liver cancer.
• Diabetes — individuals with diabetes are at higher risk due to metabolic abnormalities such as insulin resistance, chronic inflammation, and hepatic steatosis, which can progress to cirrhosis and HCC, especially when combined with other risk factors like obesity or viral hepatitis.
• Non-alcoholic fatty liver disease — fat accumulation in the liver unrelated to alcohol use can lead to non-alcoholic steatohepatitis (NASH), a progressive condition that may cause cirrhosis and subsequently HCC.
• Aflatoxin exposure — Aflatoxins are carcinogenic compounds produced by certain moulds in improperly stored food. Chronic exposure, particularly in individuals with concurrent HBV infection, significantly increases the risk of liver cancer.

How is liver cancer diagnosed?

Liver cancer is often diagnosed at a later stage, as early symptoms are usually absent or non-specific. By the time symptoms appear, significant liver damage may have already occurred. Diagnosis typically involves a combination of the following methods: 

• Physical examination — your doctor will begin by taking a detailed medical history and reviewing any symptoms. A physical exam may include palpation of the abdomen to detect liver enlargement, a palpable mass, or signs of chronic liver disease.
• Imaging tests — common imaging modalities include ultrasound, CT scans, and MRI. These are used to detect liver masses, assess their size and characteristics, and evaluate for vascular invasion or metastasis. Tumours smaller than 1 cm can be challenging to identify, especially without contrast-enhanced imaging.
• Blood tests — Liver function tests help assess the extent of liver damage, while tumour markers such as alpha-fetoprotein (AFP) may support the diagnosis of hepatocellular carcinoma. However, AFP is not specific and may be elevated in non-cancerous liver conditions.
• Histological confirmation — a liver biopsy may be performed if imaging and blood markers are inconclusive. The tissue is examined under a microscope to confirm malignancy. However, biopsy carries a small risk of tumour seeding along the needle tract, which is why it is generally reserved for select cases where imaging is not definitive.

What are the treatment options for liver cancer in Singapore?

Liver cancer treatment is guided by the stage of the disease, liver function, and the patient’s overall health. In Singapore, a multidisciplinary approach ensures that patients receive the most suitable combination of therapies for their condition.

• Surgical resection — surgical removal of the tumour (hepatectomy) is the primary curative option for early-stage liver cancer, typically BCLC stage 0 or A. It is offered to patients with good liver function and adequate functional reserve.
• Liver transplantation — liver transplant is recommended for selected patients with small tumours who are not suitable for resection, particularly those with underlying cirrhosis. It offers a chance of long-term survival and cure if the tumour meets transplant criteria.
• Tumour ablation — minimally invasive procedures such as radiofrequency ablation (RFA), microwave ablation, or cryoablation may be used to destroy small liver tumours. These are often suitable for patients who are not surgical candidates and can offer outcomes comparable to surgery in early-stage cases.
• Transarterial therapies
  • Transarterial chemoembolisation (TACE) delivers chemotherapy directly into the tumour’s blood supply and blocks blood flow, starving the tumour. It is commonly used in patients with intermediate-stage HCC who are not eligible for curative surgery.
  • Selective internal radiation therapy (SIRT/TARE) involves injecting radioactive beads into the liver’s arteries to deliver targeted radiation, and is considered in patients unsuitable for TACE or systemic therapy.
• Radiation therapy — external beam radiation may be used in advanced cases for symptom relief, control of local disease, or treatment of vascular invasion. It may also be considered in cases where surgery or other locoregional therapies are not feasible.
• Systemic therapy 
  • Targeted therapy (such as sorafenib or lenvatinib) is used for advanced or metastatic HCC to slow tumour progression.
  • Immunotherapy (such as atezolizumab with bevacizumab, or pembrolizumab) is now a common treatment option for unresectable liver cancer and may be used alone or in combination with other drugs.
• Supportive and palliative care — in end-stage liver cancer, the focus is on managing symptoms and maintaining comfort. Supportive care may include pain control, fluid management, nutritional support, and treating complications like ascites or hepatic encephalopathy.

Summary

Liver cancer, most commonly hepatocellular carcinoma (HCC), often arises in individuals with underlying liver disease such as hepatitis B or C, cirrhosis, or fatty liver disease. Early-stage liver cancer may not show symptoms, making timely diagnosis challenging. 

Diagnosis involves physical exams, imaging, blood tests, and in some cases, biopsy. Treatment depends on the cancer stage and liver function, with options including surgical resection, liver transplantation, tumour ablation, transarterial therapies, radiation, systemic therapy, and supportive care. 

If you have risk factors for liver cancer or are experiencing persistent abdominal symptoms, schedule a consultation with Tan Siong San Surgery for expert evaluation and personalised care.