Summary

Hepatitis B (HBV) is a complex DNA Hepadnavirus that causes both acute and chronic liver disease. It is unique among hepatitis viruses because its DNA template (cccDNA) integrates into the host hepatocyte nucleus, making complete "sterilising cure" essentially impossible with current drugs. Treatment aims for "Functional Cure" (HBsAg loss). Global Killer: Chronic HBV is the leading cause of Hepatocellular Carcinoma (HCC) worldwide, causing >880,000 deaths annually. Vaccine Preventable: It was the first "Anti-Cancer Vaccine".

Epidemiology

• Prevalence: 296 million people living with chronic HBV.
• Endemic Zones: Sub-Saharan Africa and East Asia (Vertical transmission).
• Transmission:
  1. Vertical (Perinatal): Most common cause of chronic disease globally.
  2. Sexual: Unprotected sex (MSM, sex workers).
  3. Parenteral: IV drug use, needlestick injuries.

Key Facts Table

Image: Serology Timeline

The Antigens (The Virus)

1. HBsAg (Surface Antigen): The outer coat.
   • Meaning: Infection (Acute or Chronic).
   • Rule: If Positive >6 months = Chronic Hepatitis B.
2. HBeAg (E-Antigen): A secretory protein from the core.
   • Meaning: High Infectivity (Active Replication).
   • Note: "Wild Type" virus is HBeAg Positive. "Pre-Core Mutants" are HBeAg Negative but still replicate (the "Sneaky" virus).

The Antibodies (The Defence)

1. Anti-HBs (Surface Antibody): Neutralizing antibody.
   • Meaning: Immunity (Cure or Vaccine).
   • Target: >10 mIU/mL is protective.
2. Anti-HBc (Core Antibody): Marker of exposure.
   • IgM Anti-HBc: Recent infection (<6 months). Indicates Acute Hep B or "Flare" of chronic.
   • IgG Anti-HBc: Past exposure. Persists for life.
   • Crucial Point: The Vaccine only contains Surface Antigen (S). Therefore, Core Ab is NEGATIVE in vaccinated people.

Serology Interpretation Matrix

The "Isolated Core" Conundrum (Neg HBsAg, Pos Core, Neg Surface Ab) > 1. Window Period: Resolving acute infection (HBsAg gone, Anti-HBs not yet made). > 2. Occult Hep B: Very low viral load. > 3. False Positive: Lab error.

• Action: Measure HBV DNA. If negative, give booster vaccine.

Acute Clearance (Adults)

• A robust Killer T-Cell (CD8) response destroys infected hepatocytes.
• Result: Clinical Hepatitis (Jaundice, High ALT) -> Clearance of Virus.

Chronic Tolerance (Neonates)

• The immature immune system recognizes HBsAg as "self" (Tolerance).
• Immune Tolerance Phase: High Virus (High DNA), Normal ALT, No inflammation. Lasts for decades (20-30 years).
• Immune Clearance Phase: In adulthood, the immune system wakes up and attacks.
  • Flare: High ALT + Liver damage.
  • Risk of Cirrhosis and HCC increases here.

Viral Replication Cycle

Signs of Decompensation (Cirrhosis)

Chronic Hep B is often silent until the end.

• Spider Naevi: Upper chest.
• Palmar Erythema: Red palms.
• Ascites: Fluid thrill.
• Encephalopathy: Confusion (flap).
• Caput Medusae: Dilated abdominal veins.

Extra-Hepatic Manifestations (Immune Complex Disease)

The body makes Antigen-Antibody complexes that deposit elsewhere:

1. Polyarteritis Nodosa (PAN): Medium vessel vasculitis.
2. Glomerulonephritis: Membranous Nephropathy.
3. Gianotti-Crosti Syndrome: Papular acrodermatitis in children.

Image: Management Algorithm

1. Who to Treat? (Indications)

Treatment is NOT for everyone. We treat the immune active phase to prevent cirrhosis. treatment is indicated if:

1. Cirrhosis: Treat ALL cirrhotics regardless of viral load.
2. High Viral Load: HBV DNA >2,000 IU/mL PLUS
3. Active Inflammation: ALT >30 (Males) or >19 (Females).

2. Antiviral Therapy (Nucleos(t)ide Analogues)

These suppress DNA but do not kill the cccDNA reservoir. Must be taken long-term.

• Entecavir:
  • Pro: Potent, low resistance.
  • Con: Cannot use if history of Lamivudine resistance.
• Tenofovir Disoproxil (TDF):
  • Pro: First line worldwide. Safe in pregnancy.
  • Con: Renal toxicity (Fanconi syndrome) and Bone density loss.
• Tenofovir Alafenamide (TAF):
  • Pro: Newer version. Less renal/bone toxicity.
  • Indication: Elderly, Osteoporosis, CKD.

3. Pegylated Interferon (Peg-IFN)

• Role: Immune modulator. Duration is finite (48 weeks).
• Goal: Induce HBeAg seroconversion.
• Cons: Terrible side effects (Flu-like, depression, bone marrow suppression).
• Use: Young patients (Genotype A) who want a chance at being drug-free.

4. Surveillance (The "Silent Killer")

HCC can develop WITHOUT cirrhosis in Hep B.

• Protocol: Ultrasound Liver + Alpha-Fetoprotein (AFP).
• Frequency: Every 6 months.
• Who?: All Cirrhotics, African >20y, Asian >40y, Family Hx of HCC.

1. Standard Schedule

• 0, 1, 6 months.
• Success: Anti-HBs >100 mIU/mL.
• Non-Responders: 5-10% fail to respond. Repeat the course or double the dose.

2. Post-Exposure Prophylaxis (PEP)

Scenario: Needlestick from HBsAg positive patient to unvaccinated nurse.

• Immediate Action:
  1. HBIG (Hepatitis B Immunoglobulin): Instant passive immunity.
  2. Vaccine Dose 1: Accelerate active immunity.
  3. Follow up at 1 and 2 months.

1. Reactivation (The "Rituximab Rule")

• Mechanism: Immunosuppression (especially Anti-CD20 Rituximab) kills B-Cells. The dormant Hep B virus (cccDNA) wakes up and replicates wildly.
• Result: Fulminant Hepatic Failure (High mortality).
• Prevention: Screen EVERY patient for HBsAg and Anti-HBc before chemo.
  • If Positive: Start Prophylactic Tenofovir.

2. Pregnancy & Vertical Transmission

• Risk: If mother has High Viral Load (>200,000), 90% risk to baby.
• Action:
  1. Treat Mum with Tenofovir in 3rd Trimester.
  2. Give Baby Vaccine + HBIG within 24 hours of birth.
• Breastfeeding: Safe (if baby vaccinated).

3. HDV Coinfection (Delta)

• The Parasite: Hep D needs HBsAg to replicate.
• Superinfection: A Chronic Hep B patient catches D. Result: Rapid progression to cirrhosis/failure.
• Treatment: Peg-IFN or Bulevirtide (entry inhibitor).

1. History Checklist

• Risk Factors: "Have you ever had a blood transfusion?" "Any tattoos/piercings?" "Have you lived abroad?" "Sexual partners?"
• Family Hx: "Did your mother have liver trouble?" (Vertical transmission).

2. Examination Signs (Chronic Liver Disease)

• Hands: Palmar erythema, Dupuytren's, Leukonychia.
• Face: Jaundice (Sclera), Parotid swelling.
• Chest: Spider Naevi (>5 is significant), Gynaecomastia.
• Abdomen: Hepatomegaly (Is it nodular?), Splenomegaly (Portal hypertension), Ascites.

3. Classic Viva Questions

• Q: What does HBeAg positive mean?
  • A: High infectivity and active viral replication.
• Q: A patient is HBsAg negative but Anti-HBc positive. Interpret.
  • A: Isolated Core Antibody. Could be "Window period" or "Occult Infection". Check DNA.
• Q: Why do we treat with Tenofovir?
  • A: To suppress DNA, reverse fibrosis, and prevent HCC.

"Do I have it for life?"

"If you have had it for more than 6 months, it is chronic. We likely cannot cure it completely, but we can control it perfectly with a daily tablet, just like blood pressure medication."

"Is it safe to have sex?"

"Once the virus is suppressed by medication, the risk is negligible. However, your partner should be vaccinated to be 100% safe."

"Will I get cancer?"

"The risk is higher than normal, which is why we will scan your liver every 6 months. By taking the medication, we reduce this risk dramatically."

Key Guidelines

Landmark Trials

• Marcellin et al (2008): 5-year Tenofovir trial showing reversal of fibrosis and cirrhosis regression in 74% of patients.
• REVEAL-HBV Study: Demonstrated the linear relationship between Viral Load and HCC risk (The higher the DNA, the higher the cancer risk).

12. Clinical Case Studies

Case 1: The "Healthy" Carrier

Presentation: A 35-year-old man from Nigeria attends for a routine insurance medical. He feels entirely well. Bloods:

• HBsAg: Positive.
• HBeAg: Negative.
• ALT: 18 (Normal).
• HBV DNA: 150 IU/ml (Low). Diagnosis: Chronic Infection (Inactive Carrier Phase). Management:
• Do NOT treat. (Immune system is controlling it).
• Surveillance: Ultrasound Liver + AFP every 6 months (HCC risk exists even in carriers).

Case 2: The Chemotherapy Reactivation

Presentation: A 60-year-old lady with Lymphoma is due to start R-CHOP (Rituximab). Screening:

• HBsAg: Negative.
• Anti-HBc: Positive.
• Anti-HBs: Positive. Interpretation: "Cured" past infection. Risk: Rituximab wipes out B-cells, allowing the dormant cccDNA to wake up. Action: Start Prophylactic Tenofovir alongside Chemo and continue for 12 months post-chemo. Outcome: Fulminant failure prevented.