HEPADNA VIRUS – HEPATITIS B VIRUS

HEPADNA VIRUS – HEPATITIS B VIRUS

definition – Hepatitis B virus (HBV) is a small, enveloped, partially double‑stranded DNA virus of the family Hepadnaviridae that infects hepatocytes and causes acute, chronic or fulminant hepatitis

causes – infection by HBV transmitted through infected blood or body fluids; risk factors include unsafe injections, sexual contact, perinatal exposure, contaminated needles, tattoo/piercing equipment

types of infection –

1. acute self‑limiting hepatitis (usually clears)
2. chronic hepatitis B (HBsAg persists >6 months)
3. fulminant (acute liver failure)
4. occult HBV (HBsAg negative, HBV DNA positive)

morphology –

1. virion (Dane particle) ≈ 42 nm, spherical, icosahedral core
2. outer lipid envelope derived from hepatocyte membrane, contains surface antigen (HBsAg) – “S”, “M”, “L” proteins
3. inner nucleocapsid (core) contains hepatitis B core antigen (HBcAg) and partially double‑stranded circular DNA (≈ 3.2 kb)
4. e‑antigen (HBeAg) is secreted soluble form of core protein

mode of transmission –

1. percutaneous exposure to infected blood (needle sticks, transfusion, unsafe surgery)
2. sexual contact (vaginal, anal, semen)
3. mother‑to‑child during delivery (vertical transmission)
4. sharing of personal items contaminated with blood (razors, toothbrushes)
5. tattooing, body‑piercing with non‑sterile equipment

pathogenesis – step‑wise sequence

1. HBV enters bloodstream → reaches liver via portal circulation
2. virus binds to hepatocyte surface receptor (NTCP) → endocytosis
3. nucleocapsid released, DNA transported to nucleus → repaired to covalently closed circular DNA (cccDNA)
4. cccDNA serves as template → transcription of viral mRNA (pre‑C, pre‑S, X)
5. mRNA exported to cytoplasm → translation of viral proteins (HBsAg, HBcAg, HBeAg, polymerase, X protein)
6. viral DNA synthesis (reverse transcription of pre‑genomic RNA) → formation of new nucleocapsids
7. nucleocapsids acquire envelope with HBsAg → mature virions secreted → infection spreads to neighboring hepatocytes
8. immune response (cytotoxic T‑cells) attacks infected cells → hepatocyte necrosis → clinical hepatitis

memory trick for pathogenesis – “Blood → Bind → Nucleus → Copy → Make → Pack → Release → React” (first letters B‑B‑N‑C‑M‑P‑R‑R)

clinical features –

1. incubation 45‑180 days
2. prodrome: low‑grade fever, malaise, anorexia, nausea, right‑upper‑quadrant discomfort
3. icterus (yellow sclera, skin) – may be mild or absent in acute infection
4. dark urine, pale stools, pruritus
5. hepatomegaly, tender liver edge
6. acute severe disease → fulminant hepatitis (coagulopathy, encephalopathy)
7. chronic infection – often asymptomatic, may progress to cirrhosis, hepatocellular carcinoma (HCC)

complications –

1. chronic hepatitis → fibrosis → cirrhosis
2. cirrhosis → portal hypertension, ascites, variceal bleed
3. hepatocellular carcinoma (HBV DNA integration, X protein oncogenic)
4. fulminant hepatic failure (high mortality)

laboratory diagnosis – serology (point‑of‑care or ELISA)

1. HBsAg – marker of current infection (acute or chronic)
2. Anti‑HBs (HBsAb) – immunity (post‑vaccination or recovery)
3. HBeAg – high viral replication, infectivity
4. Anti‑HBe – seroconversion, lower infectivity
5. Anti‑HBc IgM – recent infection (acute)
6. Anti‑HBc IgG – past or chronic infection
7. HBV DNA PCR – quantitative viral load, treatment monitoring
8. Liver function tests – ALT, AST ↑, bilirubin ↑, albumin ↓, prolonged PT/INR in severe disease

management (exam‑relevant points) –

1. acute self‑limited disease – supportive care, avoid hepatotoxins, monitor liver function
2. chronic hepatitis B – antiviral therapy if HBV DNA high, ALT elevated, or cirrhosis present
   • first‑line agents: Tenofovir disoproxil fumarate, Tenofovir alafenamide, Entecavir
   • pegylated interferon‑α for selected patients (no cirrhosis, good compliance)
3. fulminant hepatitis – intensive care, possible liver transplantation
4. prevention – universal newborn vaccination (HBsAg + HBIG within 12 h), safe injection practices, screening of blood donors, safe sex, counseling of pregnant carriers

life‑cycle summary (simplified numbered)

1. attachment to NTCP receptor on hepatocyte
2. endocytosis and release of nucleocapsid
3. transport of relaxed circular DNA to nucleus → cccDNA formation
4. transcription of viral RNAs (pre‑genomic and subgenomic)
5. translation of viral proteins (core, surface, polymerase, X)
6. reverse transcription of pre‑genomic RNA to DNA inside nucleocapsid
7. envelopment with HBsAg‑rich membrane
8. secretion of mature Dane particles and subviral HBsAg particles

funny memory rhyme for life‑cycle – “Stick, Slip, Zip, Flip, Pack, Wrap, Tap, Clap – HBV’s quick lap!” (Stick = attachment, Slip = entry, Zip = DNA to nucleus, Flip = transcription, Pack = protein synthesis, Wrap = assembly, Tap = release, Clap = infection spread)