Hepatitis B

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

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

Australia

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

At Risk Groups in Australia

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

Age Determimes Course of Illness

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 http://www.jimmunol.org/content/184/1/287

• The antigens expressed by infected hepatocytes are:– Surface antigen– Core antigen– E antigen (a soluble protein secreted by the virus into the

bloodstream)

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%

Chronic HBV Infection - Clinical

• Defined clinically by serological markers: HBs-Ag persisting for longer than 6 months

• Other markers are usually variable

Phases of Chronic HBV Infection1. Immune tolerant phase: the immune system doesn’t recognise surface or

e antigens and a high viral load (high HBV DNA) persisting for 20-30 years if infected perinatally or during childhood

2. HBeAg clearance phase: development of anti-Hbe (Hbe-Ag seroconversion) and development of immune response causing:

1. Liver inflammation, raised LFT’s2. Flare-ups causing jaundice3. Progression of liver disease to possible advanced liver disease if high viral load

HBV DNA > 100,000 IU/mL

3. 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

4. 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

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)

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)