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Liver Cancer: Diagnosis and Treatment by Dr Lee Guan Huei from Singapore (Part 1)

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Speaker

  • Dr Lee Guan Huei 李冠, Senior Consultant, Gastroenterology, NUH

Sponsors/Organising parties

  • 365 Cancer Prevention Society (365CPS), Singapore
  • National University Hospital (NUH), Singapore
  • National University Cancer Institute, Singapore (NCIS), Singapore

Date: 16 Oct 2021, Saturday

Time: 8-9pm (GMT +8)

We have Dr Lee Guan Huei, Senior Consultant, Gastroenterology, NUH, to talk to us about Liver cancer: Diagnosis and Treatment. This is proudly organised by 365 Cancer Prevention Society (365 CPS), National University Hospital (NUH), and National University Cancer Institute, Singapore (NCIS). 

For Part 1 of the forum, we have Dr Lee give us a short presentation about liver cancer: the causes, risk factors, diagnosis and treatment as well as complications of liver cancer. In Part 2, Dr Lee answers some of the questions posted by the audience. Read below to find out more about liver cancer and the symptoms we can look out for!

Presentation by Dr Lee Guan Huei

Introduction

Liver cancer is one of the most commonly diagnosed malignancies in Singapore, with a high mortality rate second only to lung cancer. The focus of the presentation will be on primary liver cancer, which refers to cancer that originated from the liver itself. This is unlike metastatic liver cancer, whereby the cancer spreads from another part of the body to the liver. 

Incidence of liver cancer 

The incidence of liver cancer varies widely globally, and is most prevalent in China, Korea, and Southeast Asia. 

Within Malaysia and Singapore, although it is not the leading cause of cancer, it is still relatively common.

In Singapore, it is the 4th highest cause of malignancy among males, who are also about four times more likely to develop the disease compared to females. Each year, about 400 people die from liver cancer in Singapore.

Causes of liver cancer

The following are common causes of liver cancer:

1. Hepatitis B infection

  • When a person is infected with hepatitis B, the liver could be subjected to chronic inflammation, which can lead to liver cirrhosis after about 10 years. Over time, this can also progress into liver cancer and liver failure. 
  • Out of every 10 patients with hepatitis B, 2 to 4 of them will develop liver cancer and failure without treatment.

2. Hepatitis C infection

3. Excessive consumption of alcohol

4. Non-alcoholic fatty liver disease (NAFLD)

  • Usually, a result of being overweight.
  • In Singapore, approximately 30.2% of the population is overweight.
  • In an overweight person, fats may accumulate inside the liver. This triggers the same chronic inflammatory process seen in patients with hepatitis B that leads to liver cirrhosis, and ultimately liver cancer.

5. Other chronic hepatitis (e.g. those of immune or genetic origin).

6. Certain drugs and medications

Risk factors of liver cancer

In general, long-standing inflammation of the liver can result in scarring. If the intensity of scarring becomes more and more severe, it can advance into liver cirrhosis. 

The level of scarring may be measured using a staging scale from F0 to F4.

  • F0 refers to a normal undamaged liver
  • F1 to F3 indicates the increasing intensity of liver scarring
  • F4 means that the patient’s liver is cirrhotic

If an individual is identified to be in the F4 stage, the severity of cirrhosis can then be calculated using the Child-Pugh score, which will classify patients into three separate categories:

Child-Pugh grade Severity
A Good liver function
B Moderately impaired liver function
C Advanced liver dysfunction

Grade A is the least serious, and C is the gravest. The risk for liver cancer is typically higher in the presence of more serious disease. 

Liver cirrhosis is irreversible and can lead to other conditions such as liver cancer. 

When the liver has been badly damaged, malignant cells within the liver only need to grow slightly, and other complications can readily develop. These include:

  • Swelling of the abdomen
  • Bleeding of the gastrointestinal tract
  • Rapid mortality

Symptoms of liver cancer

Liver cancer can manifest in different ways: 

  • Asymptomatic 
    • This typically suggests early stages of the disease, and is at the best time to treat it.
    • The liver is an organ located deep inside the body and will not generate pain unless it has enlarged remarkably to a big size.
    • Often picked up in hepatitis B patients during their routine check-up ultrasound scans.
  • Abdominal (local) symptoms
    • When tumour cells in the liver grow, it causes the liver to increase in size. 
    • As a result, the patient will start to experience upper abdominal pain.
    • At this time, the patient will also begin to lose weight.
  • Liver decompensation: Sudden rapid decline in liver functioning.
    • Hepatic encephalopathy: Reversible brain dysfunction associated with advanced liver failure. This is mainly due to the accumulation of toxins (that are usually cleared by the liver), affecting normal brain functions
    • Loss of normal liver functions.
    • Ascites: Accumulation of fluid in the abdomen.
    • Variceal (swollen blood vessels) bleeding into the oesophagus, a tube connecting the mouth to the stomach.
  • Rupture of cancerous liver cells
    • Severe abdominal pain
    • Bleeding
    • Shock: Life-threatening condition due to inadequate oxygen circulation throughout the body.
    • Most critical and urgent of all cases 

Patients can rapidly advance from having no symptoms, to the last stage. 

Screening in patients at high-risk for liver cancer

It is recommended that the following groups of patients go for routine screening: 

The screening consists of ultrasound scan and AFP levels, to be done every 6 months.

Based on risk, screening is encouraged for men ≥ 30 years old, and women ≥ 35 years old who fall in these high-risk groups.

Diagnosis of liver cancer

Radiological imaging scans such as CT or MRI are the most crucial diagnostic methods. 

  • If classical findings of liver cancer are discovered on the scans, treatment can begin immediately.
  • If there is uncertainty regarding whether the liver cancer is of primary or metastatic nature, a liver biopsy can be done to confirm it. 

Treatment of liver cancer

There have been many developments and improvements in the management of liver cancer in recent years. Treatment of liver cancer depends on the stage of liver cancer.

Liver cancer staging

Staging of liver cancer differs from that of other cancers, and involves the use of stages 0, A – C, and D, determined based on the severity of the condition. This in turn helps clinicians decide on the treatment target and strategy. 

Stage 0 to A

From stage 0 to A, the goal of treatment is to completely cure the patient. This can be done in several ways, which have a 5-year survival rate of up to 70%: 

Removal of liver cancer cells 

The liver can be divided into 8 segments. Cuts can be made between these segments to remove the cancerous cells with reduced bleeding. If the tumour size is small, robotic surgery/laparoscopy can be done. This involves making 5 small incisions in the liver to remove the cancerous cells.

Liver transplant

Under circumstances where a transplant is warranted, these groups of patients are likely to have other illnesses apart from liver cancer as well. 

The aim of this is to not only remove the malignant cells, but also to treat the entire diseased liver. This procedure can greatly reduce the recurrence rate of liver cancer. However, only eligible patients can undergo transplant. This is decided using the UCSF criteria.

Based on this criterion, patients with a single tumour of ≤ 6.5 cm, or 2 to 3 lesions with none > 4.5 cm and their total diameter not exceeding 8cm, as well as an absence of vascular invasion and metastasis to other organs, may qualify for liver transplant. 

Liver transplant can extend a patient’s survival by more than 5 years, without it, the majority of patients are unlikely to live longer than a year. 

RFA (Radiofrequency ablation)

This treatment strategy is used to avoid going into surgery, provided the tumour is small, and the state of liver cirrhosis is not too severe. 

A special needle is inserted directly into the tumour using image guidance e.g., ultrasound. Thereafter, a specific radiofrequency is released from the needle and used to burn the cancerous cells. This procedure can be performed under local anaesthesia.

PEI (Percutaneous Ethanol Injection)

Injection of alcohol directly into the tumour using a special needle to kill the cancer cells.

Stage B

From stage B, treatment becomes more difficult, with limited options. The following are some ways patients in stage B may be treated:

TACE (Transarterial chemoembolization)

A needle is inserted from the thigh until it reaches the tumour cells within the liver. Special beads are then injected. These beads reduce blood flow to the tumour and are also laced with chemicals that can destroy the tumour cells. This method is relatively effective in shrinking the tumour but is unable to eradicate all cancer cells. 

Yttrium 90

Yttrium 90 is a radioactive compound attached to special spheres which are also injected via the thighs to the liver tumour. This compound selectively binds and remains in liver cancer cells. 

It is a method that also has a good effect in reducing tumour size. 

Others

Alternatively, non-invasive radiotherapy may be performed, however, this may result in more side effects. 

Recently, a new method is being tested, which targets to “revert” the cancerous cell to an earlier stage by making them smaller. In doing so, more patients might be able to undergo transplant, and benefit from the good survival rates that transplant brings about. 

Later stages of liver cancer

For patients suffering from later stages of the disease (e.g. presence of metastasis to other organs), chemotherapy (systemic treatment) is the only option. This treatment method helps to control the malignant cells throughout the body. 

In the past, the outcome of this therapy was often unideal, until 15 years ago when a targeted drug was developed. 

Newer alternative forms of therapy have also emerged since then:

  • Atezolizumab, which is considered an immunotherapy, makes the immune system recognise the malignant cells as foreign and attack them. 
  • Bevacizumab prevents angiogenesis, which is the formation of new blood vessels, from occurring. 

This therapy has been able to increase overall survival from over 50% to over 70%. 

Other systemic therapies

There are also other first-line agents and second-line therapies that may be used in the treatment of liver cancer.

Prevention of liver cirrhosis is key to preventing liver cancer

It is important to remember that early detection and treatment of liver scarring can prevent its progression to liver cancer. Diagnosis of chronic liver inflammation is therefore crucial. 

Many general practitioners and clinics are able to run blood tests to determine liver function and detect hepatitis infections. Physicians can also advise regarding other potential issues such as intake of alcohol, and fatty liver during consultations. 

After diagnosis of chronic liver disease is established, regular follow-ups with a clinician are recommended for the following: 

  • Liver function tests (blood test)  
  • Ultrasound scan
  • Fibroscan
    • Determines severity of liver scarring i.e. What stage, from F0 to F4, that liver is at, without the need for a biopsy. 
    • Provides the advantage of being able to easily demonstrate the severity of scarring using a machine.
    • If initial stages of liver scarring are treated promptly, worsening of the fibrosis can be prevented, which will reduce the risk for liver cancer significantly. 

Once the reason for the scarring is identified, the cause can be treated accordingly:

  • Hepatitis B: drugs can be prescribed to control the infection. 
  • Fatty liver: lifestyle modifications can be introduced to reduce fatty deposits in the liver.
  • Alcoholism: decreasing alcohol consumption will be essential. 
  • Hepatitis C: currently, there are effective treatments available that have been shown to cure about 99% of infected individuals. Once treatment is completed, liver function can recover, thus preventing advancement into liver cancer. 

Summary

Liver cancer is a treatable disease, especially in the initial stages of the condition. In the early stage, most patients who receive therapy can either be cured completely or have their disease well-controlled. The most common causes are hepatitis B and liver cirrhosis.

Early stages of liver cancer often do not have any obvious signs and symptoms. Usually, if a patient presents with associated signs and symptoms, it is likely the person is at the late stage. Thus, early detection and treatment is of utmost importance. Patients with a high risk for liver cancer should go for routine check-ups, so that any liver tumours can be detected before they grow beyond 5 cm in size and receive timely treatment. 

What’s next in store?

See Part 2 for the Question and Answer (Q&A) segment with Dr Lee Guan Huei!

Watch the full video on 365 Cancer Prevention Society’s Facebook page!

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