National Guide

Chapter 19 | Cancer prevention and early detection

Liver cancer







National Guide to preventive healthcare for Aboriginal and <br/>Torres Strait Islander people
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      4. Liver cancer

Cancer | Liver cancer

Dr Nicole Allard, Mr Troy Combo   

Key messages

  • Liver cancerA  is usually caused by viral hepatitis (hepatitis B and C), alcoholic liver disease and/or metabolic dysfunction-associated fatty liver disease (MAFLD).1
  • Liver cancer usually occurs in a damaged liver (severe damage in the liver is called cirrhosis).1
  • Liver cancer can be prevented by vaccination for hepatitis B, treatment of hepatitis B and C and by modifying alcohol intake, diet and other health risk behaviours.
  • All adult Aboriginal and Torres Strait Islander people whose immune status is not known should be offered testing for hepatitis B.2
  • If a person has no history of vaccination, is non-immune and there is no evidence of infection with hepatitis B, they should be offered vaccination for hepatitis B.3
  • People with a diagnosis of hepatitis B should be monitored at least yearly and started on antiviral treatment if there are signs of liver damage or cirrhosis.3
  • Hepatitis C can be prevented by harm-reduction strategies, including needle exchange programs.
  • Targeted screening of people at higher risk of hepatitis C should be offered.4
  • All Aboriginal and Torres Strait Islander people with hepatitis C should be offered treatment to cure the infection. Direct-acting antiviral (DAA) hepatitis C treatments are easy for most people to take and cure more than 95% of people.5
  • The early detection of liver cancer through surveillance (six-monthly ultrasound with or without α-fetoprotein [AFP]) can lead to people receiving treatments that can cure the cancer and/or increase survival.1
  • Six-monthly liver cancer surveillance by liver ultrasound, with or without AFP, should be offered to Aboriginal and Torres Strait Islander people who are suitable for and would consider treatment if a diagnosis of liver cancer (hepatocellular carcinoma [HCC]) was made and who:
    • have cirrhosis
    • have hepatitis B and are aged 50 years or older
    • are aged 40 years or older with a family history of one or more first-degree relatives with liver cancer or with a high-risk hepatitis B virus (HBV) genotype individually confirmed (eg C4) or epidemiologically likely.1
A Primary liver cancer/HCC throughout this topic will be referred to as ‘liver cancer’. The liver can be a site for spread from other cancers (ie secondary liver cancer), which is not included in this topic.
Type of preventive activity - Immunisation
Who/target population What When Strength of recommendation Key source(s) and reference(s) Rationale/key considerations informing recommendation
All infants Hepatitis B vaccination as per the National Immunisation Program Schedule At birth and at age <24 hours and 2, 4 and 6 months for all infants Strong Australian guideline6 Immunisation prevents the transmission of hepatitis B and therefore prevents liver cancer
All hepatitis B non-immune adults Offer immunisation if not previously vaccinated
Consult the Australian immunisation handbook if previously immunised (non-responder; see Non-responders to hepatitis B vaccine in Useful resources		 As clinically indicated Strong Australian guideline6 Immunisation prevents infection with hepatitis B and therefore prevents liver cancer
Babies born to women with hepatitis B
AND
People who have a recent high-risk exposure to hepatitis B (eg occupational exposure)		 Offer hepatitis B immunoglobulin After birth (preferably within 12 hours and in addition to hepatitis B birth dose)
AND
After exposure (preferably within 72 hours)		 Strong Australian guideline6 The use of immunoglobulin (passive vaccination) in conjunction with hepatitis B vaccine decreases the risk of mother-to-child (vertical) transmission of hepatitis B and in cases of high-risk exposure
Type of preventive activity - Screening for hepatitis B 
Who/target population What When Strength of recommendation Key source(s) and reference(s) Rationale/key considerations informing recommendation
All adults not previously screened or whose hepatitis B status is not known (see Chapter 13: Sexually transmissible infections and blood-borne viruses and Chapter 5: Preconception and pregnancy care, Pregnancy care) Test for hepatitis B using three serology markers: hepatitis B s antigen (HBsAg), and anti-HBs and anti-HBc antibodies

Record status

Offer immunisation if non-immune and not vaccinated

Consult the Australian immunisation handbook if previously immunised (non-responder; see Non-responders to hepatitis B vaccine in Useful resources)		 Opportunistically, antenatally, as part of general or sexual health checks
Does not need to be repeated if immune		 Strong Australian guidelines2 One-time screening has been shown to be cost-effective down to a low population prevalence for hepatitis B and is essential to identify people at increased risk of liver cancer and in order to offer monitoring, antiviral treatment and or cure (hepatitis C)
Type of preventive activity - Screening for hepatitis C 
Who/target population What When Strength of recommendation Key source(s) and reference(s) Rationale/key considerations informing recommendation
Adults at higher risk of hepatitis C (see Box 1 and Chapter 13: Sexually transmissible infections and blood-borne viruses and  Chapter 5: Preconception and pregnancy care, Pregnancy care) Recommend testing for hepatitis C antibodies (anti-HCV) plus HCV RNA if antibodies are detected Opportunistically, at least annually, sexual health check or during antenatal care Strong Australian guidelines4 Many people are not aware of having hepatitis C infection

One-time screening has been shown to be cost-effective down to a low population prevalence for both hepatitis C and hepatitis B and is essential to identify people at increased risk of liver cancer and in order to offer monitoring, antiviral treatment and or cure (hepatitis C)
Type of preventive activity - Screening
Who/target population What When Strength of recommendation Key source(s) and reference(s) Rationale/key considerations informing recommendation
All people who are HCV antibody positive and have had a negative hepatitis C virus (HCV) RNA test in the past
AND
If there is ongoing history of higher risk of hepatitis C infection		 Offer HCV RNA test Opportunistically Strong Australian guideline4 People at ongoing risk of hepatitis C and a history of past exposure, including previous cure, need to be monitored for reinfection
All adults with increased risk of cirrhosis and liver cancer from common conditions (eg diabetes and obesity) Conduct liver function tests (LFTs) At least annually Good practice point Australian guideline1 Diabetes causes MAFLD and is associated with an increased risk of liver cancer
There are more likely to be multiple drivers of liver disease
For adults at risk of rare causes of liver disease (eg with a family history of autoimmune hepatitis, Wilson’s disease haemochromatosis) Conduct LFTs
Arrange liver ultrasound if LFTs abnormal		 As per risk factors and clinical indication Good practice point Australian guideline1 Other rarer causes of liver disease can contribute to liver cancer risk
Type of preventive activity - Behavioural
Who/target population What When Strength of recommendation Key source(s) and reference(s) Rationale/key considerations informing recommendation
All people with abnormal LFTs Assess for the cause of liver disease, including for hepatitis B and C, diabetes, obesity, alcohol use and other rarer causes

Arrange liver ultrasound to assist diagnosis of MAFLD

Conduct non-invasive tests for fibrosis*		 As clinically indicated Good practice point Australian guideline 7 LFTs are often ordered in clinical practice and become a starting point for a query about underlying liver disease

MAFLD is a diagnosis made after excluding viral hepatitis and other causes of liver damage. There is no accepted diagnostic test, but liver ultrasound may confirm steatosis
All adults with risk factors for liver cirrhosis Examine for signs of liver disease and consider non-invasive test for cirrhosis* Every two years for people with viral hepatitis Good practice point Australian guidelines7 In early cirrhosis there are usually no symptoms

All people with cirrhosis need optimal management and HCC surveillance

Non-invasive tests have been validated for different types of liver disease
All adults with cirrhosis who are willing and suitable for receive treatment (as defined in the Key source guidelines) if liver cancer is diagnosed Liver ultrasound with or without AFP Six monthly Strong Australian guidelines1 Cost-effective analysis has been done in the general population

Early detection of liver cancer in at-risk individuals can lead to improved outcomes with curative or targeted therapies
All people living with hepatitis B who:
  • are aged over 50 years
OR
  • are aged 40 years and over and have a first-degree family history of liver cancer
OR
  • are aged 40 years and over with a high-risk HBV genotype individually confirmed (eg C4) or epidemiologically likely
 Liver ultrasound with or without AFP Six monthly Conditional Australian guidelines 1 Early detection of liver cancer in at-risk individuals can lead to improved outcomes with curative or targeted therapies
Adolescents and adults Assess the quantity and frequency of alcohol consumption and advise about safer levels of alcohol consumption to reduce long-term risk of alcohol-related harm (refer to Chapter 1:
Healthy living and health risks, Alcohol and Chapter 7: The health of young people)		 Opportunistically and as part of annual health check Conditional Australian guideline8 Drinking alcohol increases the risk of liver cancer
The level of risk increases as more alcohol is consumed
Adolescents and adults Assess smoking status and encourage smoking cessation (see Chapter 2: Healthy living and health risks, Smoking) Opportunistically Good practice point Australian guideline9 Smoking increases the risk of liver cancer and smoking cessation may reduce the risk of liver cancer
People with overweight/obesity or metabolic syndrome Advise of the risks of MAFLD and promote weight reduction strategies (see Chapter 15: Overweight and obesity) Opportunistically and as clinically indicated Good practice point Australian guideline9 Obesity is associated with MAFLD, which is a risk factor for liver cancer
Losing weight may decrease overall risk for liver cancer in an individual
People at higher risk of hepatitis B or C infection (see Box 1) Provide counselling on harm minimisation, including immunisation for hepatitis B, and promote peer education strategies around safer sex and injecting drug use where relevant (refer to Chapter 13: Sexually transmissible infections and blood-borne viruses) Opportunistically Strong National guidelines2,4 Preventing the transmission of viral hepatitis reduces the risk of liver cancer associated with hepatitis B and C
Type of preventive activity - Medication
Who/target population What When Strength of recommendation Key source(s) and reference(s) Rationale/key considerations informing recommendation
All people with chronic hepatitis B infection Assess and treat as per guidelines (see Hepatitis B diagnosis and next steps in Useful resources) As clinically indicated Strong Australian guideline3 Antiviral treatment in eligible people with hepatitis B reduces the risk of liver cancer by 75%
Pregnant women with hepatitis B with a viral load >200,000 IU/mL Prescribe antiviral treatment for prophylaxis of mother-to-child transmission In the last trimester Strong Australian guideline3 Prevention of mother-to-child transmission, therefore chronic infection in infants and future risk of liver cancer
All people with hepatitis C infection for six months or longer, as well as those with risk factors for hepatitis C who have HCV RNA on testing regardless of duration of infection Provide counselling and offer treatment while addressing other health needs As clinically indicated Strong Australian guideline5 Antiviral treatment in eligible people with hepatitis C reduces the risk of cirrhosis and liver cancer

*Non-invasive tests for fibrosis have largely replaced liver biopsy, which is rarely performed. Non-invasive tests used include transient elastography (TE; FibroScan®) and risk calculators such as the aspartate aminotransferase to platelet ratio index (APRI score) and Fibrosis-4 (FIB-4) score. These calculators use blood tests (LFTs and full blood examination, with or without age) and can be found online (see Useful resources). They provide a good alternative to assess people living in rural or remote settings where access to TE is limited.

There has been a recent reclassification of liver disease in 2023.10 The term ‘fatty liver’ and reference to ‘alcoholic’ in older terms were recognised as stigmatising language. This new naming system (Box 2) has not yet been widely adopted and this document has mostly used MAFLD because it is familiar to users of the guide, but it is important to note that there is a mixture of old and new nomenclature in the guidelines and other literature. Clinical software may still use older terms. These new names will become more commonly used in the future to describe liver disease that is not related to viral hepatitis. 

 

Box 1. People at higher risk of hepatitis C infection: Who to screen

  • People who inject drugs or who have ever injected drugs
  • People in custodial settings
  • People with tattoos or body piercings
  • Children born to mothers with hepatitis C virus (HCV) infection
  • Sexual partners of a person with HCV infection (individuals at higher risk of sexual transmission include men who have sex with men and people with HCV–HIV coinfection)
  • People with evidence of liver disease (persistently elevated alanine aminotransferase level)
  • People who received a blood transfusion or organ transplant before 1990
  • People with coagulation disorders who received blood products or plasma-derived clotting factor treatment products before 1993
  • People with HIV or hepatitis B virus infection
  • People who have had a needlestick injury

Box 2. New terminology for liver disease not related to viral hepatitis10
New name Old name Explanation
Steatotic liver disease (SLD) Fatty liver disease Overall term to describe when there is steatosis or a build up of fat in the liver. This causes inflammation and raised liver function tests. SLD can be from metabolic causes, alcohol or drug induced or due to an unknown cause or combination of causes.
Metabolic dysfunction-associated steatotic liver disease (MASLD) Fatty liver, non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated fatty liver disease (MAFLD), non-alcoholic steatohepatitis (NASH) Where there is metabolic dysfunction associated with the process of steatosis or fat build up in the liver. Metabolic dysfunction includes diabetes, insulin resistance and other cardiovascular risk factors
MASLD and alcohol-induced injury (Met-ALD) A mixture of metabolic and alcohol-related terms Describes a mixed cause of liver disease.
Alcohol-associated or -related liver disease (ALD) Alcoholic liver disease (ALD) When the person has a higher alcohol intake (eg four or more standard drinks a day or 28 or more per week), the alcohol is more likely to be the main cause of the liver injury.
Drug-induced liver injury Fatty liver caused by medication or other drugs This can include prescribed medicines or complementary therapies that can cause liver injury.

Hepatitis B

  • Consensus recommendations on the management of hepatitis B
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Hepatitis C

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HCC surveillance guidelines

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Background

Most primary liver cancer is preventable. Liver cancer is often diagnosed late and has very poor survival. Aboriginal and Torres Strait Islander people are twice as likely to develop liver cancer, are more likely to be diagnosed late and have a poorer survival at five years than non-Indigenous Australian people.11 In some areas, like the Northern Territory, Aboriginal people are five-fold more likely to develop liver cancer than the non-Indigenous population.12

Liver cancer usually starts in a damaged or cirrhotic liver. Damage to the liver is the result of inflammation and can be caused by chronic hepatitis B or C infection or MAFLD (previously non-alcoholic and/or fatty liver disease; see Box 2), which may or may not be associated with alcohol use or other rarer causes of liver disease. Some people with hepatitis B may develop liver cancer without liver damage. Liver cancer in Aboriginal and Torres Strait Islander people is commonly associated with at least two risk factors, for example hepatitis C and diabetes. Aboriginal and Torres Strait Islander people are also more likely to have liver cancer due to hepatitis B, alcohol and diabetes than non-Indigenous Australians.13

Hepatitis B and C are both more common in Aboriginal and Torres Strait Islander people than most non-Indigenous people, and this is why screening is recommended, especially for those born before universal hepatitis B vaccination became available in 2000 and for those at higher risk of infection. Notification rates for newly diagnosed hepatitis B in Aboriginal and Torres Strait Islander people are declining due to the impact of vaccination programs.14

Risk factors for hepatitis B infection include: children of mothers with hepatitis B; household or other close contacts of people with hepatitis B; people with liver disease; and people at risk of blood-borne viruses, such as men who have sex with men (MSM), people who inject drugs and people living with HIV(see Chapter 13: Sexually transmissible infections and blood-borne viruses).

Risk factors for hepatitis C infection include:

  • a history of ever injecting drugs
  • time in prison
  • tattoos and body piercings in unregulated high-risk settings (eg prisons or backyard tattooing)
  • recipients of blood products, tissues or organs prior to February 1990 in Australia or anytime overseas
  • MSM and people living with HIV.

 

Interventions to prevent liver cancer include preventing hepatitis B and hepatitis C infection through effective preventive activities, which include:

  • vaccination (hepatitis B)
  • harm reduction measures such as needle exchange programs and encouraging the single use of needles by people who inject drugs
  • preventing infants getting hepatitis B at birth
  • screening and providing treatment to people already living with hepatitis B and C
  • behavioural interventions for people drinking harmful levels of alcohol or who have obesity (to prevent MAFLD).

One-time hepatitis B screening of people whose immune status is not known, which has been shown to be cost-effective down to a low population prevalence,2,3 and targeted screening of people at higher risk of hepatitis C4 are essential to identify people at increased risk of liver cancer in order to offer monitoring and antiviral treatment as well as hepatitis B vaccination for non-immune adults. Surveillance (secondary prevention through early detection of liver cancer) by liver ultrasound with or without AFP is recommended for all Aboriginal and Torres Strait Islander people with cirrhosis, with a family history of liver cancer, who are aged 50 years and older with hepatitis B or aged 40 years and older with a high-risk hepatitis B genotype.

Hepatitis B vaccination prevents infection, which is a major risk factor for liver cancer. Universal infant vaccination is administered at birth and at age two, four and six months, and is available through the National Immunisation Program. Hepatitis B vaccination is recommended for all non-immune Aboriginal and Torres Strait Islander adults and is free in most jurisdictions through state-funded programs. There is ongoing advocacy for nationally consistent fully funded access to vaccination.

Prevention of mother-to-child transmission of HBV

All pregnant women should be tested for hepatitis B. If women have hepatitis B, they need further tests, including viral load, to determine whether antiviral treatment should be recommended during pregnancy. Infants born to hepatitis B s antigen-positive mothers should receive hepatitis B immunoglobulin within 12 hours of birth and hepatitis B vaccination within 24 hours.

Hepatitis B antiviral therapy

Hepatitis B antiviral therapy is not needed for all people but can be used in people with liver damage/cirrhosis or an inflamed liver. Antiviral therapy can reverse liver damage and prevent liver cancer. The treatment can be prescribed by trained GPs in the community through the section 100 (s100) scheme.

Hepatitis C oral DAA therapy

DAAs have been available in Australia since 2016. Although a range of antiviral therapies were previously available, DAAs are more effective, much better tolerated and cure most people. They are tablets taken for 8–12 weeks.5 As well as preventing transmission, curing hepatitis C prevents liver damage and reduces the risk of liver cancer. All adults with chronic hepatitis C (infection that lasts longer than six months), as well as those with risk factors for hepatitis C who have HCV RNA on testing regardless of the duration of infection, are eligible for treatment.5 This includes people who inject drugs and people who are re-infected. The treatments are well tolerated and result in cure more than 95% of the time. They can be prescribed by GPs and nurse practitioners who are experienced in this area or in consultation with a liver specialist, and are dispensed in the community through the section 85 (s85) scheme.15 There are programs in prisons that are testing and treating people during incarceration. For clinical guidelines, see Useful resources.

Reduction in alcohol consumption

Any person with longstanding harmful alcohol consumption can be at risk of developing liver damage (cirrhosis) and at risk of liver cancer. Harmful alcohol consumption can also add to damage from liver disease from other causes. Interventions to reduce harmful alcohol consumption are important in all people, but especially important where there is another risk factor for liver cancer. If someone has liver damage or cirrhosis, the best advice is to avoid alcohol.

Healthy diet and exercise

Diet, healthy weight/weight reduction and exercise are all important in preventing or reducing the harmful effects of MASLD. Although MASLD is common, it does not necessarily lead to further damage and cirrhosis.

Not smoking or smoking cessation

Cigarette smoking is an independent risk factor for liver cancer.

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