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Background

Hepatitis B is a double stranded DNA virusÌýthat 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 horizontallyÌýby exposure to infected body fluidsÌý(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 daysÌý(mean of 90 days).^5,6Ìý

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

• Infants infected perinatally usually have no symptoms or signs.ÌýInfection 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.ÌýThe 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 toleranceÌý-Ìýcharacterised 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.Ìý
• Immune clearanceÌý-Ìý(immune active) where theÌýimmune system attempts to clear virus, resulting in liver damage. ÌýThis phase is characterised by fluctuating ALT, and variable levels of HBV DNA.
• Immune controlÌý- where the immune system successfully controls virus, resulting in low levels of HBV DNA. ÌýIn this stage patients are usually HBeAb positive, with normal liver function tests. ÌýIf complete eradication is achieved (in children ~0.5-1%/year), the patient will eliminate HBsAg and develop HBsAb, indicating resolution of infection.
• Immune escapeÌý- (immune reactivation) where the hepatitis B virus ‘escapes’ immune control and begins to replicate again, despite the presence of HBeAb. ÌýThis may result in high levels of HBV DNA. ÌýLiver damage may again occur in this phase.

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

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

• 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% whereÌýmothers 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 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 AustraliaÌý(given atÌýbirth, 2, 4 and 6 months)Ìýand in many countries of origin for humanitarian entrants.ÌýÌýare available. Ìý

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 Ìý Ìý ÌýHBsAg+, HBcIgM+, +/- HBeAg, +/- clinical illness
• Chronic infectionÌý HBsAg present >6m, HBcIgM-, HBcIgG+ or anti HBc total+, +/- HBeAg
• Past infection Ìý Ìý ÌýÌý HBsAb+, HBcIgG+
• Past vaccination Ìý 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:

• HBsAgÌý(infection)
• HBsAbÌý(immunity - either due to past infection or immunisation)
• HBcAbÌý(clarifies if immunity due to infection or vaccination)

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

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

• LFT,ÌýHBcAb 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 areÌý
• 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 negativeÌý(seeÌý)
• 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
• (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 andÌýα¹ó±Ê
• 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
• α¹ó±ÊÌý12 monthly
• HBsAg/sAb and eAg/eAb 12-monthlyÌý- may revert back to HBeAg+

HBeAg positive and normal LFT

• ReviewÌýby gastroenterology, this is the profile in the immune tolerant stage
• LFT 6-monthly
• α¹ó±ÊÌý12-monthly
• HBsAg/sAb and eAg/eAb 12-monthlyÌý
• 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 monitoringÌý
• α¹ó±ÊÌý12-monthly
• HBsAg/sAb and eAg/eAb 12-monthlyÌý
• 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 errorÌý
• 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)Ìý
• If HBV-DNA is positive - annualÌýLFT andÌýα¹ó±Ê, 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 errorÌý
• 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

• TheÌýÌýprovides advice and support for health providers diagnosing hepatitis B infections
• Ìý- ASHM (Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine) resource
• St. Vincent's Hospital Department of Gastroenterology - or in format.
  

References