Background

Hepatitis B is a double stranded DNA virus that causes liver inflammation (acute and/or chronic hepatitis). In people with chronic infection around 25% will develop cirrhosis that progresses to end stage liver disease¹ and there is a 200-fold increase in risk of hepatocellular carcinoma (HCC).² Adults with chronic hepatitis B infection acquired in childhood develop HCC at a rate of 5% per decade.³

Hepatitis B may be transmitted vertically (from mother to child) or horizontally by exposure to infected body fluids (blood or semen). Horizontal transmission is important in children < 5 years and household or sexual contacts of people with Hepatitis B infection.⁴

The incubation period is 45-160 days (mean of 90 days).^5,6 

Clinical manifestations depend on the age at acquisition, viral load and host immune status. The virus itself is probably not cytopathogenic; most complications are the result of the  host immune response attempting to destroy viral infected cells.

• Infants infected perinatally usually have no symptoms or signs. Infection produces a clinical illness in approximately 5-15% of children aged 1-5 years and 33-50% of older children and adults.^7,8 Between 0.1-1% of acute infections will progress to fulminant hepatitis.⁸
• Age at infection is the most important determinant of chronic infection. The rate of progression from acute infection to chronic infection is around 90% in hepatitis B acquired perinatally or in infancy, 25-50% in children aged 1-5 years and 6-10% in older children and adults.³

Chronic hepatitis B infection is described in four stages

• Immune tolerance - characterised by high levels of hepatitis B virus (HBV) and presence of HBeAg. There is minimal immune response to presence of virus, and therefore low risk of liver damage in this stage. 
• Immune clearance - (immune active) where the immune system attempts to clear virus, resulting in liver damage.  This phase is characterised by fluctuating ALT, and variable levels of HBV DNA.
• Immune control - where the immune system successfully controls virus, resulting in low levels of HBV DNA.  In this stage patients are usually HBeAb positive, with normal liver function tests.  If complete eradication is achieved (in children ~0.5-1%/year), the patient will eliminate HBsAg and develop HBsAb, indicating resolution of infection.
• Immune escape - (immune reactivation) where the hepatitis B virus ‘escapes’ immune control and begins to replicate again, despite the presence of HBeAb.  This may result in high levels of HBV DNA.  Liver damage may again occur in this phase.

The risk of vertical transmission is dependent upon the maternal viral load. Women who are HBeAg positive have a 90% risk of transmission in the absence of immunoprophylaxis.⁹  Even in the presence of appropriate immunoprophylaxis, mothers with a high viral load (HBV DNA >200,000 IU (10⁶ copies)/mL)) have a transmission risk of 8-30%.¹⁰

In Australia, pregnant women are screened for Hepatitis B infection at their first antenatal visit.  

• Infants of mothers with Hepatitis B infection (HBsAg +) receive immunoprophylaxis with hepatitis B immunoglobulin (HBIg) and vaccine on the day of birth at the same time, but in separate thighs. HBIg should preferably be given within 12 hours of birth, and definitely within 48 hours. Hepatitis B vaccine should preferably be given within 24 hours of birth, and definitely within 7 days. This regimen results in seroconversion rates of more than 90% in neonates, even with concurrent administration of HBIg⁴ and reduces the risk of vertical transmission by more than 95%.¹⁰ In the absence of neonatal vaccination, transmission rates (from mother to neonate) are 5-20% where mothers are HBsAg + and HBeAg -, and 70-90% where mothers are HBsAg + and HBeAg +.³
• All infants of women with hepatitis B infection should then receive hepatitis B vaccine according to the National Immunisation Program Schedule and be screened for hepatitis B infection (HBsAg, HBsAb) at 9-12 months of age.¹¹

Hepatitis B vaccination is part of the routine immunisation schedule in Australia (given at birth, 2, 4 and 6 months) and in many countries of origin for humanitarian entrants. Worldwide vaccination schedules are available.  

Prevalence

The prevalence rate of hepatitis B infection is highest in South-East Asia and Sub-Saharan Africa.¹² Studies in refugee cohorts in Australia suggest the prevalence of chronic hepatitis B infection is:

• 3-16% in people from Africa%^13-18
• 3.5%-9.7% in people from South & South East Asia^14,19,20
• 0-2.8% in people from Afghanistan, Pakistan and Iraq.^14,21,22
• 4.6-16% in people from Myanmar^19,22
• 0-14.7% in people from Tibet and India²²

While hepatitis B was common in clinical practice over the period 2005 - ~2012, it has been much less frequent in children since this time, likely reflecting the introduction of HBV immunisation in Humanitarian source countries for Australia.

Summary of hepatitis B serology

• Acute infection      HBsAg+, HBcIgM+, +/- HBeAg, +/- clinical illness
• Chronic infection  HBsAg present >6m, HBcIgM-, HBcIgG+ or anti HBc total+, +/- HBeAg
• Past infection        HBsAb+, HBcIgG+
• Past vaccination   HBsAb+, HBcAb-

Assessment

• Risk factors for exposure - family history hepatitis B (especially maternal), transfusions, healthcare-related, tattooing, sexual transmission where relevant
• Recent vaccinations - e.g. recent offshore hepatitis B vaccination may result in transient detection of HBsAg
• Family/household hepatitis B immunisation status and household arrangements
  
• Symptoms - usually asymptomatic, clarify if past acute illness or current symptoms (fever, fatigue, anorexia, nausea, RUQ pain, usually anicteric). Papular acrodermatitis is a rare presentation of acute hepatitis B infection in children
• Consider other conditions affecting/affected by hepatitis B - hepatitis C (HCV), HIV, schistosomiasis, active tuberculosis, latent tuberculosis infection, medications affecting the liver
• Examination - stigmata chronic liver disease, liver, spleen

Screening

All children attending Immigrant health clinic are screened for:

• HBsAg (infection)
• HBsAb (immunity - either due to past infection or immunisation)
• HBcAb (clarifies if immunity due to infection or vaccination)

A titre of HBsAb >10 IU/L indicates adequate immunity. If HBsAb is <10 IU/L, exclude infection, then give hepatitis B catch-up vaccination; see Immunisation Handbook

If children are HBsAg + they should have further tests to determine acute vs chronic infection and presence/absence eAg to give information about infectivity:

• LFT, HBcAb IgM and IgG, HBeAg, HBeAb
• HBV DNA for viral load

Screen for hepatitis A immunity (to determine if hepatitis A vaccination required - 2 doses 6 months apart for long-term immunity) and consider risk factors and screening for HIV, HCV, and schistosomiasis in children with hepatitis B.

Management

• All children with acute hepatitis B and clinical illness need immediate referral to Gastroenterology (note that acute hepatitis B is rare in childhood)
• Explanation/education/counselling. Translated information sheets are available
• Advice not to share razors, toothbrushes, nail clipper or earrings/piercings
• Advice re: blood spills and infection risk- suggest gloves to clean blood spills and disinfection with diluted (1:10) household bleach.⁴
• Advice to notify their treating doctors when starting medications
• Advice for adolescents re: alcohol consumption and using barrier contraception
• Immunise against Hepatitis A if serology negative (see Immunisation handbook)
• Screen and vaccinate household contacts against hepatitis B (vaccines 0-19 are funded, and adult vaccinations funded for household contacts). Check for seroconversion after immunisation
• Remember hepatitis if starting hepatotoxic drugs- particularly anti-tuberculous therapy
• Hepatitis B (sAg positive) is a notifiable disease (Group B - written notification within 5 days)
• The clearance rate of HBsAg is 0.5-1 % per year and the clearance of HBeAg is 2-5% per year in children.

HBeAg negative and normal LFT

• Review at primary care level. This is the profile in the immune control stage
• Annual LFT and αFP
• Refer to gastroenterology if elevated ALT

HBeAg negative and abnormal LFT

• Review by gastroenterology, ongoing management in specialist setting. The concern is immune escape/reactivation
• HBV DNA - if viral load high, gastroenterology review for consideration of liver biopsy
• LFT monitoring
• αFP 12 monthly
• HBsAg/sAb and eAg/eAb 12-monthly - may revert back to HBeAg+

HBeAg positive and normal LFT

• Review by gastroenterology, this is the profile in the immune tolerant stage
• LFT 6-monthly
• αFP 12-monthly
• HBsAg/sAb and eAg/eAb 12-monthly 
• HBV DNA if seroconversion from eAg+ to eAb+

HBeAg positive and abnormal LFT

• Review by gastroenterology, ongoing management in specialist setting, this is the profile in the immune active stage
• Ultrasound
• LFT monitoring 
• αFP 12-monthly
• HBsAg/sAb and eAg/eAb 12-monthly 
• HBV DNA if seroconversion from eAg+ to eAb+

Treatment has been less well studied in children than adults, although it may be indicated in a few circumstances, such as the immune clearance phase, where there is evidence of liver damage on biopsy.²³

Other issues

Isolated HBcAb +

• Test error 
• The window stage of acute hepatitis B infection (antiHBcAb is the first antibody to develop)
• Resolved hepatitis B with waning levels of HBsAb
• Remote hepatitis B infection with persisting HBV DNA (without detectable HBsAg) 
• If HBV-DNA is positive - annual LFT and αFP, refer to gastroenterology if elevated ALT. Patient education about possible reactivation if immunosuppressed, transmission prevention (although risk not clear) and advice against blood donation
• If HBV-DNA is negative - consider giving either a booster dose of vaccine or a repeat primary course to see if patient has a "booster" anamnestic response (HBsAb >=10 IU/L on serology at least one month later)

Isolated HBsAg +

• Test error 
• Post immunisation (within 4 weeks) - suggest retest serology in 1-2 months
• Early infection - if repeat test the same, and no recent immunisation, suggest HBV DNA to confirm.

Resources

• The HepBHelp website provides advice and support for health providers diagnosing hepatitis B infections
• B positive - ASHM (Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine) resource
• St. Vincent's Hospital Department of Gastroenterology - The Hepatitis B Story in booklet or in video format.
  

References

• References