Hepatitis B

Virology And Pathogenesis

DNA virus; member of Hepadnaviridae family.
Genome contains four open reading frames: S (surface), C (core), X (regulatory), P (polymerase).
Inherently non-cytopathogenic; hepatocyte injury primarily immune-mediated.
Cytotoxic T-lymphocytes target viral antigens (HBcAg, HBeAg) expressed on hepatocyte surface, inducing cell lysis.
Perinatal acquisition typically induces robust immune tolerance, minimizing acute inflammation while permitting high viral replication.

Perinatal (vertical) transmission constitutes primary pediatric infection route; highest risk if mother HBeAg-positive.
Horizontal transmission via contaminated blood, sexual contact, institutional care.
Chronicity risk inversely related to age of acquisition: ~90% in infants, 20-30% in children 1-5 years, <5% in adults.
Incubation period ranges 45-160 days.

Pediatric infections predominately asymptomatic.
Prodromal phase features serum sickness-like syndrome: arthralgia, macular/urticarial rashes, papular acrodermatitis (Gianotti-Crosti syndrome).
Acute symptomatic phase: anorexia, nausea, malaise, fatigue, jaundice.
Extrahepatic manifestations: polyarteritis nodosa, membranous glomerulonephritis, leukocytoclastic vasculitis, Guillain-Barré syndrome, aplastic anemia.

Marker Profile	Clinical Interpretation
HBsAg(+), Anti-HBc IgM(+), Anti-HBs(-)	Acute infection.
HBsAg(+), Anti-HBc IgG(+), Anti-HBs(-)	Chronic infection (persistence >6 months).
HBsAg(-), Anti-HBc IgG(+), Anti-HBs(+)	Resolved past infection; immune.
HBsAg(-), Anti-HBc(-), Anti-HBs(+)	Immunity secondary to vaccination.
HBeAg(+)	Active viral replication; high infectivity.

Phase	Serologic Profile	Clinical Features	Management
Immune Tolerant	HBeAg(+); High HBV DNA (>20,000 IU/mL); Normal ALT.	Minimal hepatic inflammation/fibrosis. Highly infectious.	Monitor regularly. Therapy ineffective/not indicated.
Immune Active (Clearance)	HBeAg(+); High HBV DNA (>20,000 IU/mL); Elevated ALT.	Active inflammation. Cytotoxic T-cell activation. Fibrosis progression risk.	Liver biopsy indicated. Antiviral treatment recommended.
Inactive Carrier	HBeAg(-); Anti-HBe(+); Low/undetectable DNA (<2000 IU/mL); Normal ALT.	Minimal inflammation. Seroconversion achieved.	Continued monitoring. Risk of hepatocellular carcinoma persists.
Reactivation	HBsAg(+); HBeAg(-); Anti-HBe(+); DNA >2000 IU/mL; Elevated ALT.	Precore/core promoter mutants. Active inflammation.	Liver biopsy indicated. Long-term treatment required.

Acute infection requires supportive care; monitor synthetic function assessing for acute liver failure.
Goal of chronic therapy: Suppress viral replication (undetectable DNA), induce HBeAg to anti-HBe seroconversion, prevent cirrhosis and hepatocellular carcinoma.
Treatment strictly indicated for immune-active phase (persistently elevated ALT, DNA >20,000 IU/mL, active fibrosis).

Drug Class	Specific Agents	Clinical Utility And Limitations
Interferons	Peg-Interferon-alfa	Immunomodulatory. Finite 48-week course. Significant adverse effects (cytopenias, depression). No viral resistance.
Nucleoside Analogues	Entecavir	First-line pediatric agent (approved >2 years). Potent viral suppression. High barrier to resistance.
	Lamivudine	Historically used. Currently discouraged due to high emergence of YMDD mutant resistance (64% at 3 years).
Nucleotide Analogues	Tenofovir disoproxil	First-line agent (approved >12 years). Excellent safety profile. Negligible resistance risk.

Universal Vaccination: Recombinant vaccine administered at birth, 1-2 months, and 6 months. Induces protective anti-HBs titers (>10 mIU/mL) in >90-95% of recipients.
Perinatal Prophylaxis: Hepatitis B immunoglobulin (HBIG) plus Hepatitis B vaccine administered at separate anatomical sites within 12 hours of birth for infants born to HBsAg-positive mothers. Prevents >95% of transmissions.
Maternal Therapy: Administer antiviral therapy (tenofovir or telbivudine) during third trimester to HBsAg-positive pregnant women demonstrating high viral loads (HBV DNA >200,000 IU/mL) to reduce vertical transmission risk.

Liver Cirrhosis: Develops in 3-10% of children with chronic infection.
Hepatocellular Carcinoma (HCC): Risk elevated 100-fold in chronic carriers; occurs independently of cirrhosis.
Fulminant Hepatic Failure: High mortality (>30%). Risk significantly amplified by concurrent Hepatitis D virus superinfection or emergence of precore mutant strains. Requires urgent liver transplantation.