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Transcript
Primary liver cancer
and chronic hepatitis B
Primary liver cancer is now one of the top ten causes of cancer death in Australia. Median
survival from the most common form of liver cancer, hepatocellular carcinoma (HCC), is just
five months.
Chronic hepatitis B (CHB) is the most common cause of
liver cancer worldwide.1 Almost 800,000 Australians die
from hepatitis B infection every year.2 Recent migration
from countries with a high prevalence of hepatitis B has
increased the local incidence of CHB and HCC3, and
screening people born in endemic countries is effective in
identifying risk and linking to care.4 A large proportion of
HCC is preventable through vaccination against hepatitis B.
Chronic hepatitis B prevalence in Australia,
by risk group9
HBsAg prevalence
in risk group (%)
Group
2.4 (average)
People born in high or
intermediate-prevalence
countries
Hepatitis B transmission
Hepatitis B can be transmitted:
Proportion
of CHB in
Australia (%)
•vertically, from mother to child.
3.6 (Asia and Pacific
regions)
2.7 (Africa/Middle
East)
56
1.0 (Europe)
•horizontally, through:
- close household contact with an infected person
- sexual contact with an infected person
- skin piercing
- medical procedures
- open wounds from an infected individual.
5
At a global level, mother to child transmission is responsible
for the largest number of infections.6 80-90 per cent of
infections contracted before one year of age lead to chronic
infection, compared with 30-50 per cent of childhood
infections and less than 5 per cent of infections contracted
in adulthood.7 In countries where CHB infection is
uncommon in the general population, most infections are
acquired in adulthood, are self-limiting and result in clearing
the virus from the blood and liver and long-lasting immunity
to re-infection.8 A small proportion of adults who become
infected (< 5%) fail to clear the infection and may have
ongoing viral replication.8
Working together to lessen the impact of cancer
Aboriginal and Torres Strait
Islander people
3.7
9
People who inject drugs
4
6
Men who have sex
with men
3
4
Non-Aboriginal Australianborn individuals*
0.3
19
Other or not stated
1.0
6
*excluding those belonging to the other priority populations listed
above; CHB, chronic hepatitis B; HBsAg, hepatitis B surface
antigen
Additional reading
Further references to hepatitis B and liver cancer are
available in B Positive. All you wanted to know about
hepatitis B. A guide for primary care providers.10
Fact sheet
Primary liver cancer and chronic hepatitis B
Symptoms of hepatitis B infection
Hepatitis B treatment
The acute infection phase is commonly asymptomatic,
but some people experience:
Acute hepatitis B generally requires supportive care only.
•jaundice
•dark urine
•extreme fatigue
•nausea
•vomiting and abdominal pain for a period of several weeks.
Acute liver failure occurs rarely, but can lead to death.5
Hepatitis B diagnosis
The hallmark of hepatitis B infection is the detection
of the hepatitis B surface antigen – HBsAg in the serum.
Acute hepatitis B virus (HBV) infection is characterised by
the presence of HBsAg and immunoglobulin M (IgM)
antibody to the core antigen, HBcAg. During the initial phase
of infection, patients are also seropositive for hepatitis B e
antigen (HBeAg). HBeAg is usually a marker of high levels of
viral replication. The presence of HBeAg indicates that the
blood and body fluids of the infected individual are highly
contagious.
Chronic hepatitis B infection is characterised by the
persistence of HBsAg for at least six months (with or
without concurrent HBeAg). Persistence of HBsAg is the
principal marker of risk for developing chronic liver disease
and HCC later in life.5
See Figure 1.
Ascertaining the extent of liver fibrosis is critical for decisionmaking in patients with chronic liver disease. Transient
elastography (TE, or FibroScan) has replaced liver biopsy in
the clinical armamentarium for the diagnosis and
assessment of liver fibrosis.11
Figure 1: Natural history of chronic hepatitis B infection
The Australasian Society of HIV Medicine runs courses
for general practitioners wishing to become hepatitis B
prescribers.
Prevention of hepatitis B and liver cancer
A comprehensive public health response to hepatitis B
needs to integrate primary, secondary and tertiary
prevention into a coordinated response.
Primary prevention of hepatitis B and liver cancer
Hepatitis B vaccination and reduced exposure to the virus
(e.g. through screening blood donors and safe injection
techniques) are effective approaches to primary prevention.
It is recommended that all newborns receive the first dose
of hepatitis B vaccine within 24 hours of birth, followed by
a further three doses in infancy, at 2, 4 and 6 months of age.
Adolescents not vaccinated as children, and adults at risk
of exposure to HBV or at risk of severe disease, should
also be targeted for vaccination. For further details, see
the Australian Immunisation Handbook
Secondary prevention: hepatitis B and
management
As antiviral treatment can significantly reduce the
incidence of HCC, screening and improved management
of chronic viral hepatitis are integral components of HCC
prevention.
N further
No
progression
HCC
Normal liver
Chronic hepatitis B infection may require treatment with
antiviral agents to slow the progression of cirrhosis, reduce
the incidence of liver cancer and improve long-term survival.5
Current treatments are rarely curative, but suppress
replication of the virus, so antiviral treatments are long-term
(typically lifelong).
Chronic hepatitis B
Cirrhosis
End stage
liver disease
Working together to lessen the impact of cancer
The goals of therapy in HBV-infected patients include
reducing the level of viraemia and a correction of liver
dysfunction, with treatment indicated in people with
chronic hepatitis B infection who have elevated ALT levels
and elevated viral loads.8 Adequate control of chronic
hepatitis B leads to a reduction in the risk of fibrosis and
cirrhosis, HCC development and end stage liver disease.
Markers of successful therapy include the clearance of
HBeAg, seroconversion to anti-HBe antibodies, and a
reduction in the circulating viral load.8
Fact sheet
Primary liver cancer and chronic hepatitis B
Tertiary prevention: screening for HCC
Liver ultrasound (US) is the test of choice for HCC screening,
and combining this with serum alpha-fetoprotein (AFP)
measurement increases HCC detection by a further 6-8 per
cent.12 Six monthly follow-up is required as a negative
screening result cannot reliably exclude the presence of HCC.13
Current management guidelines recommend that HCC
surveillance should be offered to people with cirrhosis,
or other HCC risk factors, including:
•Asian men over the age of 40
•Asian women over the age of 50
•African people older than 20 years of age
•People with a family history of primary liver cancer.14,15
Population-level models of hepatitis B
screening and treatment
Preventing HCC is contingent on educating and engaging
the affected population to become active participants in
their care.
South-West Sydney has the highest burden of both
chronic hepatitis B16 and HCC17 in Australia.
B Positive is a local program based in South-West Sydney
that uses a CHB disease registry to support evidence-based
and timely patient follow up and referrals. With the help of
local general practitioners, 21% of enrolled participants are
on antivirals and treatment uptake is almost four times the
national average.18
References
1. Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment,
and current and emerging prevention and control measures. J Viral Hepat
2004;11(2):97-107.
11.Chon YE, Choi EH, Song KJ, Park JY, Kim do Y, Han KH, et al. Performance of
transient elastography for the staging of liver fibrosis in patients with chronic
hepatitis B: a meta-analysis. PLoS One 2012;7(9):e44930.
2. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global
and regional mortality from 235 causes of death for 20 age groups in 1990 and
2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet
2012;380(9859):2095-128.
12.De Masi S, Tosti ME, Mele A. Screening for hepatocellular carcinoma. Dig Liver
Dis 2005;37(4):260-8.
3. MacLachlan J, Allard N, Towell V, Cowie B. The burden of chronic hepatitis B virus
infection in Australia, 2011. Australian and New Zealand Journal of Public Health
2013:online
14.Sherman M. Pathogenesis and screening for hepatocellular carcinoma. Clin Liver
Dis 2004;8(2):419-43, viii.
4. Thomson MD, Hoffman-Goetz L. Cancer information comprehension by Englishas-a-second-language immigrant women. J Health Commun 2011;16(1):17-33.
5. World Health Organization. Hepatitis B fact sheet no 204. Geneva: WHO, 2012.
13.Sherman M. Hepatocellular carcinoma: epidemiology, risk factors, and screening.
Semin Liver Dis 2005;25(2):143-54.
15.Gastroenterological Society of Australia and Digestive Health Foundation.
Australian and New Zealand chronic hepatitis B (CHB) recommendations. Clinical
update In: Foundation DH, editor, 2010.
6. Custer B, Sullivan SD, Hazlet TK, Iloeje U, Veenstra DL, Kowdley KV. Global
epidemiology of hepatitis B virus. J Clin Gastroenterol 2004;38(10 Suppl
3):S158-68.
16.MacLachlan J, Cowie B. Hepatitis B Mapping Project: Estimates of chronic
hepatitis B prevalence and cultural and linguistic diversity by Medicare Local,
2011 – National Report. In: ASHM, editor. Sydney: Australasian Society for HIV
Medicine, 2013 40.
7. World Health Organization (WHO). Immunization surveillance, assessment and
monitoring.: WHO.
17.Alam N, Chen W, Baker D, Bishop J. Liver Cancer in New South Wales. In:
Cancer Institute NSW, editor. Sydney: Cancer Institute NSW, 2009.
8. Ganem D, Prince AM. Hepatitis B Virus Infection — Natural History and Clinical
Consequences. New England Journal of Medicine 2004;350(11):1118-29.
18.MacLachlan J, Cowie B. Hepatitis B mapping project: Estimates of chronic
hepatitis B diagnosis, monitoring and treatment by Medicare Local. National
Report 2012/13 In: Australasian Society for HIV Medicine, editor. Hepatitis B
mapping project Sydney Australasian Society for HIV Medicine (ASHM) and
Victorian Infectious Diseases Reference Laboratory (VIDRL), 2015.
9. MacLachlan JH, Allard N, Towell V, Cowie BC. The burden of chronic hepatitis B
virus infection in Australia, 2011. Aust N Z J Public Health 2013;37(5):416-22.
10.Matthews G, Robotin M, Allard N, editors. B Positive-all you wanted to know about
hepatitis B: a guide for primary care providers. second ed. Sydney: ASHM, 2014.
Working together to lessen the impact of cancer
Cancer Institute NSW PO Box 825, Alexandria, NSW 1435
t +61 (0)2 8374 5600 f +61 (0)2 8374 3600 e [email protected]
www.cancerinstitute.org.au
© Cancer Institute NSW 2015. Created May 2015. While every effort has been made to provide accurate information, this document is not intended as a substitute for medical advice.
Contact your doctor if you have any concerns. See www.eviq.org.au for our full disclaimer and any updates.