Describe hepatitis B virus with its antigens, transmission, serological profile and prevention.

Structure and Antigens

• Hepatitis B virus is a hepadnavirus — a 42 nm DANE particle with an outer envelope and an inner core, containing partially double-stranded circular DNA and its own DNA polymerase with reverse transcriptase activity
• It is the smallest DNA virus genome of medical importance, and the only DNA virus that replicates through an RNA intermediate — which is why nucleoside analogues developed for HIV also work against it
• CccDNA (covalently closed circular DNA) persists in the hepatocyte nucleus as a stable template, which is why infection can be suppressed but rarely cured and why treatment is usually long-term

Transmission and Natural History

• Parenteral — transfusion, unsafe injections, needlestick injury, shared needles among drug users, dialysis, tattooing, ear piercing and shared razors. Hepatitis B is roughly 100 times more infectious than HIV by needlestick
• Sexual transmission, and perinatal (vertical) transmission from mother to infant, which is the dominant route in high-prevalence countries
• The age at infection determines the outcome — this is the key epidemiological fact. Over 90% of infected neonates become chronic carriers, about 30% of young children, but fewer than 5% of immunocompetent adults. The immature immune system fails to clear the virus but also fails to produce symptoms
• Incubation 45 to 180 days (average about 75), much longer than hepatitis A
• Acute hepatitis — a prodrome with anorexia, nausea, malaise and sometimes arthralgia, urticaria and a serum-sickness-like illness from immune complexes, then jaundice; fulminant hepatic failure in about 1%
• Chronic infection — progresses through immune-tolerant, immune-active and inactive carrier phases; leads to cirrhosis and to hepatocellular carcinoma, which HBV can cause without cirrhosis because the viral DNA integrates into the host genome
• Extrahepatic disease — polyarteritis nodosa and membranous glomerulonephritis, both immune-complex mediated

Interpreting the Serological Profile

Prevention and Treatment

• The vaccine is recombinant HBsAg produced in yeast — safe, highly effective, and included in the pentavalent vaccine in India's Universal Immunisation Programme, with a birth dose within 24 hours
• It was the first vaccine shown to prevent a cancer, since preventing chronic infection prevents hepatocellular carcinoma
• Anti-HBs above 10 mIU/mL indicates protection; non-responders (about 5 to 10%) require revaccination
• Perinatal prophylaxis — hepatitis B immunoglobulin plus the first vaccine dose within 12 hours of birth to infants of HBsAg-positive mothers, with antiviral therapy for the mother if the viral load is high; this prevents the great majority of vertical transmission
• Post-exposure prophylaxis after needlestick — immunoglobulin and vaccine according to the source and the recipient's antibody status
• Treatment of chronic infection — tenofovir or entecavir (potent, with a high barrier to resistance) and pegylated interferon-alpha. Treatment suppresses rather than cures, because cccDNA persists, so it is usually long-term or lifelong
• Other measures — safe injection practice, screening of blood donors, sterilisation of instruments, and universal precautions

Hepatitis D and Comparison with Other Hepatitis Viruses

• Hepatitis D (delta agent) is a defective RNA virus that requires the HBsAg envelope of hepatitis B to assemble and transmit — so it can only infect someone who has hepatitis B
• CO-infection (both acquired together) usually resolves as the hepatitis B does; superinfection of an established hepatitis B carrier causes severe acute hepatitis and rapid progression to cirrhosis, and is far more dangerous
• Preventing hepatitis B prevents hepatitis D entirely — the hepatitis B vaccine protects against both

Applied Aspects

• Vaccinate all healthcare workers and students and check the antibody response; this is the single most effective protection against an occupational infection that is 100 times more transmissible than HIV
• Give the birth dose within 24 hours; delay is the commonest reason perinatal transmission is not prevented, and it must not wait for maternal test results
• Screen for HBsAg in every pregnant woman, and arrange immunoglobulin and vaccine for the infant where positive
• Screen for HBV before immunosuppression — particularly before rituximab, chemotherapy, transplantation or anti-TNF therapy; reactivation can cause fulminant hepatic failure and is preventable with prophylactic antivirals
• Do not diagnose "carrier" and discharge; chronic infection requires long-term monitoring for viral load, liver function, fibrosis and hepatocellular carcinoma surveillance by ultrasound and alpha-fetoprotein
• Unsafe injections and unscreened blood remain significant sources in India, and single-use syringes, auto-disable devices and proper waste disposal prevent more infection than any treatment