1. Hepatitis B

2. Epidemiology
HBV infection acquired early in life is a major cause of chronic liver disease, including cirrhosis, and primary liver cancer
The hepatitis B virus is the 2nd most important known human carcinogen, after tobacco
Up to 400 million people, mostly in the Asia Pacific region, are chronically HBV– infected

3. Australia
There is currently an epidemic of chronic Hepatitis B in Australia
In Australia up to 160,000 are chronically infected with HBV – half are from endemic countries of the Asia Pacific region
Unlike HIV and Hep C (sexy infections) there is no comprehensive national Hepatitis B public health strategy
Universal hepatitis B vaccination for infants and people at high risk of infection has been implemented in Australia since 2000

4. Australia

5. At Risk Groups in Australia
IV drug users (16% of prevalence but 40% of all new acute cases. Usually co-infected with hepatitis C increasing risk of chronic illness and advanced liver disease)
People born in an endemic region
Asia and the Pacific Islands (50% of prevalence)
Africa, the Middle East, and the Mediterranean region
Homosexual men (8%)
Indigenous - the virus was discovered in 1965 in Australian aborigines. They make up 2% of the total population but 16% of the total prevalence of chronic hepatitis B.
Prisoners

6. At Risk Groups in Australia

7. Transmission of HBV Saliva, semen, blood
Perinatal – risk of disease is 80% from mother +ve to HBsAg and HNeAg
To children through household contact
In healthcare settings and sharing of contaminated equipment

8. Age Determimes Course of Illness

9. Virology
Hep B is a DNA virus and uses reverse transcription to copy its DNA
The virus does not kill cells but expression of antigens causes both cytotoxic CD8+ T cell lysis (minor defence) and secretion of cytokines (IFN-γ and TNF-α ) causing non-cytolytic viral inhibition (major defence) see
The antigens expressed by infected hepatocytes are:
Surface antigen
Core antigen
E antigen (a soluble protein secreted by the virus into the bloodstream)

10. Acute HBV Infection - Clinical
Symptoms: primarily jaundice after 8 weeks (range 6-12 weeks) but other symptoms can appear such as malaise, nausea, vomiting, LOA, arthralgia, myalgia
Serological markers
HBV DNA early marker (2 weeks after infection)
HBs-Ag can be detected 1 month after infection
anti-HBc IgM and Hbe-Ag at 8 weeks
LFT’s: ALT, AST
Mortality is 1%

12. Chronic HBV Infection - Clinical
Defined clinically by serological markers: HBs-Ag persisting for longer than 6 months
Other markers are usually variable

13. Phases of Chronic HBV Infection
Immune tolerant phase: the immune system doesn’t recognise surface or e antigens and a high viral load (high HBV DNA) persisting for years if infected perinatally or during childhood
HBeAg clearance phase: development of anti-Hbe (Hbe-Ag seroconversion) and development of immune response causing:
Liver inflammation, raised LFT’s
Flare-ups causing jaundice
Progression of liver disease to possible advanced liver disease if high viral load HBV DNA > 100,000 IU/mL
Low/non replicative phase: almost complete eradication of the virus with normal LFT’s and low HBV DNA, minimal liver damage and low risk of developing advanced live disease
Reactivating phase: immunosuppression typically is the cause of reactivation of the infection, inflammation and raised ALT/AST with increasing HBV DNA but no return of Hbe-Ag. Advance liver disease can develop if HBV DNA is > 100,000 IU/mL

14. Treatment of Hep B The targets of treatment are:
Inhibit viral DNA replication
Enhance the immune response (as already mentioned, the main immune response is the non-cytolytic one involving cytokines)

15. Ongoing Treatment
Medicare only pays for monotherapy, which is suboptimal - cf successful combination therapies subsidised for “sexier” Hep C and HIV
Nucleoside monotherapy has been associated with development of resistance
LFT’s and serology are performed every 3 months to determine effectiveness of treatment (not covered by Medicare)