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🦠 VIRAL HEPATITIS - Complete Microbiology Notes

(Exam-Oriented | Jawetz + Harrison's se)

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📌 OVERVIEW - Ek Nazar Mein

Mnemonics: "A aur E = Fecal-oral" | "B, C, D = Blood/Body fluids"

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🅐 HEPATITIS A VIRUS (HAV)

Virology:

• Family: Picornaviridae, Genus: Hepatovirus
• Non-enveloped, +ssRNA, 27-32 nm, cubic symmetry
• Only 1 serotype - isliye vaccine effective hai
• Stable: Acid (pH 1), ether, 60°C/1 hour tak stable
• Inactivated by: Autoclaving (121°C/20 min), boiling (5 min), UV radiation, formalin, chlorine (10-15 ppm)

Pathogenesis:

• Fecal-oral route se enters → small intestine → hepatocytes mein replicate → cell-mediated immunity se liver damage (virus directly cytopathic nahi)
• Viremia: Incubation period ke end mein
• HAV particles stool mein jaundice se 2 weeks PEHLE aate hain

Clinical Features:

• Acute self-limiting illness - NEVER chronic
• 3 phases: Prodromal (anorexia, nausea, fever, dark urine) → Icteric (jaundice) → Recovery
• Fulminant hepatitis bahut rare (<0.1%)

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🅑 HEPATITIS B VIRUS (HBV) ⭐ (Most Important for Exam)

Virology:

• Family: Hepadnaviridae
• Dane particle (42 nm) = complete virion
  • Outer envelope: HBsAg (surface antigen) = Australia antigen (1964 Blumberg discovery)
  • Inner core (27 nm): HBcAg + HBeAg + HBV DNA + DNA polymerase (reverse transcriptase activity)
• Partial dsDNA genome - 3.2 kb, circular
• 4 open reading frames: S gene (surface), C gene (core + precore), P gene (polymerase), X gene
• cccDNA (covalently closed circular DNA) = nuclear reservoir - chronicity ka basis

Antigens and Antibodies (MOST IMPORTANT for exam):

HBsAg (Surface Antigen):

• First marker to appear (2-6 weeks before symptoms)
• Indicates: Active HBV infection (acute OR chronic)
• Persists >6 months = Chronic infection
• Disappears with recovery
• Australia antigen - Blumberg ne discover kiya (Nobel Prize 1976)

Anti-HBs (Antibody to Surface Ag):

• Appears after HBsAg disappears (or after vaccination)
• Indicates: Recovery + Immunity OR Vaccination
• Window period = HBsAg gone, Anti-HBs not yet appeared - iss time sirf anti-HBc IgM positive hoga

HBcAg (Core Antigen):

• NEVER detected in serum (only in liver biopsy)
• But antibody (anti-HBc) is detectable

Anti-HBc:

• IgM anti-HBc = Acute/Recent infection (including window period!)
• IgG anti-HBc = Past infection or chronic infection
• Anti-HBc IgM = Best marker for acute HBV infection

HBeAg (e Antigen):

• Derived from pre-core region
• Indicates: High replication, High infectivity
• Present in early acute hepatitis and chronic active hepatitis
• Seroconversion (HBeAg → Anti-HBe) = Good prognostic sign

Anti-HBe:

• Indicates decreasing viral replication
• Low infectivity

HBV DNA:

• Most sensitive marker of viral replication
• PCR-based assay: detects as few as 10-100 virions/mL
• Used for monitoring antiviral therapy

📊 Serological Patterns Table (EXAM MOST ASKED):

Key Exam Trick: Vaccination mein sirf Anti-HBs hoga, anti-HBc NAHI - yahi vaccination ko past infection se alag karta hai!

HBV Mutations (Exam Important):

• Pre-core mutant: Stop codon at nucleotide 1896 → HBeAg nahi banta → HBeAg-negative chronic hepatitis B with active disease - anti-HBe positive bhi ho sakta hai
• Surface gene mutant: Vaccine escape mutants

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🅒 HEPATITIS C VIRUS (HCV)

Virology:

• Family: Flaviviridae, Genus: Hepacivirus
• Enveloped, +ssRNA, 9.4 kb genome
• 6 major genotypes (1-6), 100+ subtypes - genotype 1 most common worldwide, India mein genotype 3
• High mutation rate → quasi-species → vaccine development impossible
• Envelope proteins E1 and E2 - hypervariable region (HVR1) mein mutations

Lab Diagnosis:

• Anti-HCV (ELISA): Screening test - current ya past infection indicate karta hai
  • No IgM class assay of clinical value (unlike HAV/HBV)
  • 3rd/4th generation ELISA most sensitive
• HCV RNA (PCR):
  • Qualitative: Confirms active infection, "window period" mein bhi positive
  • Quantitative (viral load): Treatment monitoring
  • Positive in 1-2 weeks after infection (vs anti-HCV takes 6-8 weeks)
• HCV Genotyping: Treatment duration/regimen decide karne ke liye
• RIBA (Recombinant Immunoblot Assay): Confirmatory test for anti-HCV

Key Points:

• 70-80% chronicity - most common cause of chronic hepatitis globally
• Most common cause of adult liver transplantation (HCV cirrhosis)
• Extrahepatic manifestations: Cryoglobulinemia, membranoproliferative GN, lichen planus
• Screening: All persons born 1945-1965 (USA baby boomer screening)

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🅓 HEPATITIS D VIRUS (HDV) - Delta Agent

Virology:

• DEFECTIVE/SATELLITE VIRUS - cannot replicate alone
• Needs HBsAg as its envelope (coat)
• -ssRNA circular genome, 1.7 kb - smallest human RNA virus genome
• Contains HDAg (delta antigen) - small (p24) and large (p27) forms
• Only 1 serotype

Two Forms:

1. Co-infection: HDV + HBV simultaneously → Usually self-limiting, complete recovery
2. Superinfection: HDV infects chronic HBV carrier → Most severe! High risk of fulminant hepatitis and cirrhosis

Lab Diagnosis:

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🅔 HEPATITIS E VIRUS (HEV)

Virology:

• Family: Hepeviridae (pehle Calicivirus-like classify kiya tha)
• Non-enveloped, +ssRNA, 7.5 kb
• 4 major genotypes:
  • Genotype 1, 2: Humans only, endemic areas (India, Asia, Africa)
  • Genotype 3, 4: Zoonotic (pigs, deer, camels), non-endemic areas
• India + Asia = Waterborne outbreaks (monsoon flooding ke baad!)

Special Features:

• Pregnant women mein most dangerous - mortality 10-20% (vs 1-2% general population)
• HAV jaisa dikhta hai clinically - fecal-oral, no chronicity (in immunocompetent)
• No vaccine routinely available (HEV 239 = Hecolin - only China mein licensed)
• Secondary person-to-person spread = RARE (HAV se different!)
• Zoonotic reservoir = primarily pigs

Lab Diagnosis:

• Anti-HEV IgM: Acute HEV infection
• Anti-HEV IgG: Past infection / immunity
• HEV RNA (PCR): Acute infection confirmation, especially in immunocompromised

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🔬 LAB DIAGNOSIS - Summary Approach

Acute Hepatitis Workup:

Step 1: Anti-HAV IgM + HBsAg test karo
  → Anti-HAV IgM (+) = Acute HAV
  → HBsAg (+) = Acute/Chronic HBV

Step 2: Agar dono negative →
  → Anti-HBc IgM check (window period HBV)
  → Anti-HCV + HCV RNA (acute HCV)
  → Anti-HEV IgM (HEV especially pregnancy/endemic area)

Step 3: Agar HBsAg (+) → Anti-HDV check (severe/fulminant cases)

Chronic Hepatitis Workup:

• HBsAg + Anti-HCV (primary screen)
• If HBsAg (+): HBeAg, Anti-HBe, HBV DNA quantitative
• If Anti-HCV (+): HCV RNA qualitative → if positive, HCV RNA quantitative + genotype

Common Lab Methods:

Anamnesis tip: ALT > AST in viral hepatitis (opposite of alcoholic hepatitis where AST:ALT > 2:1)

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💉 PREVENTION (Exam Important)

HAV Prevention:

• Active immunization: Inactivated HAV vaccine (Havrix, Vaqta)
  • 2 doses: 0 and 6-12 months

  • 95% effective, protects for 20+ years

  • Killed virus vaccine (not live attenuated in routine use)
• Passive immunization: Normal Immunoglobulin (IG) = pre/post-exposure
• General: Safe water, sanitation, hand hygiene, food safety (heat >85°C/1 min)

HBV Prevention:

• Active immunization (Most effective!): Recombinant HBsAg vaccine (Engerix-B, Recombivax)
  • 3 doses: 0, 1, 6 months schedule
  • Recombinant DNA vaccine = yeast mein HBsAg produce karte hain
  • Anti-HBs ≥10 mIU/mL = protective
  • WHO recommend: Universal infant vaccination
• Post-exposure prophylaxis (PEP):
  • HBIG (Hepatitis B Immune Globulin) + HBV vaccine simultaneously (different sites)
  • Needlestick, sexual exposure, infants born to HBsAg(+) mothers
• Birth dose: 1st dose within 24 hours of birth (for MTCT prevention)
• HBIG alone for infants of HBsAg(+) mothers + complete vaccine series

Key Exam Point: HDV bhi HBV vaccine se rukta hai (kyunki HDV ko HBV ki zaroorat hoti hai). Lekin chronic HBV carriers ko HDV superinfection se vaccine protect NAHI karta.

HCV Prevention:

• No vaccine available (due to high mutability, quasi-species)
• Blood/plasma screening mandatory
• Harm reduction: needle exchange programs for IV drug users
• No HCIG available
• Safe injection practices, infection control in healthcare settings

HEV Prevention:

• Safe water supply, sewage treatment
• No routine vaccine (HEV 239 / Hecolin - China only)
• Pregnant women: Avoid travel to endemic areas
• Cook pork thoroughly (genotypes 3, 4)

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🎯 HIGH-YIELD EXAM POINTS (Quick Revision)

One-liners:

1. Australia antigen = HBsAg (Blumberg, 1964) - Nobel Prize 1976
2. Window period mein only anti-HBc IgM positive hota hai
3. Dane particle = complete infectious HBV virion (42 nm)
4. HBeAg = infectivity marker (high replication)
5. Anti-HBs alone (no anti-HBc) = vaccination
6. HDV = defective virus, needs HBsAg envelope
7. Superinfection > Coinfection (severity mein) for HDV
8. HCV = most common cause liver transplant in adults
9. HEV = most dangerous in pregnancy (10-20% mortality)
10. HAV, HEV = fecal-oral; never chronic
11. HCV = 70-80% chronicity (highest)
12. HBcAg serum mein NAHI milta - only in liver

Vaccine Comparison:

Chronicity Risk:

• HBV: Perinatally acquired = 90% chronicity, Adults = 5-10%
• HCV: 70-80% (any age)
• HAV, HEV = Never chronic (HAV mein occasional relapsing hepatitis)

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