Hepatitis B Infection in Children

HBV

• Hepatitis B virus is a double stranded DNA virus that replicates by reverse transcription and can cause acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC).
• 5% of the world's population is infected with HBV; subsaharan Africa chronic carrier rates are 9 to 20%.
• HBV replicates in liver and spleen, with high rates of mutation.  The best markers of active HBV replication are HBeAg and HBV DNA.

Contagion

• Highest HBV concentrations (in descending order): blood, semen, saliva, vaginal secretions, breast milk, urine, tears, CSF.
• Spread by:  shared needles, accidental needle sticks, promiscuous sexual activity, mucosal or broken skin contact, maternal-neonatal vertical transmission (or horizontal in child less than 5 years of age).
• HBV survives in dried state for one week or longer.
• Natural history of HBV infection depends on the host's immunity and on the virus

Presentation

Incubation of 45-60 days
Asymptomatic
Anorexia, nausea, emesis
Arthralgias, macular rash
Polyarteritis nodosa, membranous glomerulonephritis, cryoglobinemia
Fatal hepatitis
Chronic hepatitis
HCC (hepatocellular carcinoma)

Persistence of HBV infection

Occurs when there is a weak antiviral response
• younger age of infection (newborn 80-90%, infant 50%, children 20%, adult 2%)
• Most hepatitis resolves in 3 months
• 5% of HBV patients go on to prolonged HBV infection, cirrhosis, HCC
• Coinfection with HBC increases the likelihood of fulminant hepatitis and HCC
• HBV carrier: persistence of HbsAg for more than 6-12 months
• 30% of patients with chronic hepatitis will have spontaneous reactivation of their disease
• Clinical signs of chronic hepatitis are unreliable, often silent disease
• Need to distinguish chronic HBV hepatatis versus healthy HbsAg carrier
• Chronic HBV hepatitis usually has HbeAg and HBV DNA present
• Serum aminotransferase levels can be helpful but not reliable
• Most definitive is liver biopsy with immunocytochemical stains, HbcAg in liver, HBV DNA in liver tissue

Diagnosis

• HBV DNA

First detectable serological marker (2-3 weeks before HbsAg)
Not widely available
Indicates active replication
• HBsAg

Positive 1-10 weeks after exposure; several weeks before symptoms
May persist for several months
Indicates acute or chronic infection present
• HBeAg

Appears within a week of HbsAg
Usually disappears within 2 weeks
Indicates a highly infectious state
• IgM-antiHBc

First antibody to appear
May be the only marker of HBV infection in "window" between HbsAg and anti HBs
Not present in perinatal HBV infection
• IgG-antiHBc

Appears in convalescent phase
Can be present after resolved or chronic infection
Not present due to immunization
• AntiHBe

Appears after antiHBc
May persist for years
Indicates less infectious carrier
• AntiHBs

Present in late convalescence
Indicates development of immunity and recovery from infection
Also present in immunized patients

Interferon: viral inhibition and immune stimulation

• Noted to be deficient in patients who go on to chronic HBV infection
• Recombinant alpha interferon is only treatment approved in US and Europe for chronic HBV
• Side effects: mild "flu-like" symptoms to severe (autoimmune)
• Expensive
• Reponses vary: transient, partial, complete
• 4-6 months subcutaneous injections qod
• 30-40% of patients improve; better chance of improvement if high initial serum aminotransferase and low serum HBV DNA; worse prognosis: Oriental patients, children, immunodeficient individuals, highly viremic patients.
• Pretreatment with high dose steroids may help in some cases

Hepatitis B Vaccine

• Only recombinant form is made in the US
• Stable, safe, highly immunogenic, effective
• Childhood immunization is much more effective, need less vaccine
• Unclear at present when boosters are needed -- perhaps after 10 years, but not yet recommended
• Perinatal HBV infection if more than 95% preventable if exposed infants receive HBIg and HBV vaccine at birth (followed with vaccine doses at 1-2 months and at 6-18 months for a total of 3 doses).
• Postimmunization screening at age 1 year because 4.8% become carriers despite appropriate vaccination and HBIg administration

Screening

• In 1988, the CDC recomended that all pregnant women be screen for HepBsAg and that infants of all positive mothers be immunized as above
• In 1991, AAP recommended that the immunization be universal, with catch-up immunization of all children
• For most recent guidelines, consult the AAP's Red Book: The Recommendations of the Committee on Infectious Disease

Orders

• Screen for HbsAg and antiHBs
• Consider screen for HAV
• If positive, confirm with comprehensive HBV panel:
• HbsAg
• HbeAg
• antiHBs
• antiHBc
• antiHBe
• (IgM anti-HBc)
• Liver function tests
• HCV
• HBV DNA
• HIV testing
• No alcohol consumption
• Minimize tylenol
• Check household contacts and immunize anyone who is not immune
• Consider GI referral, if severe liver biopsy.

Recommended Reference

Acknowlegment