Hepatitis B-High Yield Guide
Hepatitis B – High Yield Guide for Medical Students
Hepatitis B virus (HBV) is a DNA virus that causes both acute and chronic liver disease. It remains a major global health concern, particularly in Asia and Africa. Understanding its virology, transmission, diagnosis, and management is crucial for medical students and clinicians.
Virology & Structure
- Family: Hepadnaviridae
- Genome: Partially double-stranded DNA
- Envelope with HBsAg (Hepatitis B surface antigen)
- Core with HBcAg (core antigen)
- HBeAg: secreted antigen indicating active replication
HBV Lifecycle & Drug Targets (High-Yield)
Lifecycle Steps:
- Attachment & Entry – HBV binds to NTCP receptor on hepatocytes.
- Uncoating – Viral DNA released into cytoplasm.
- Transport to Nucleus – Conversion of relaxed circular DNA (rcDNA) to covalently closed circular DNA (cccDNA).
- Transcription – Host RNA polymerase transcribes viral mRNAs and pregenomic RNA (pgRNA).
- Translation – Viral proteins synthesized in cytoplasm.
- Reverse Transcription – pgRNA → DNA via viral reverse transcriptase.
- Assembly & Release – Mature virions secreted via ER–Golgi pathway.
Drug Targets
| Drug Class | Target Step | Examples |
| Nucleos(t)ide analogues | Reverse transcription (pgRNA → DNA) | Tenofovir, Entecavir, Lamivudine |
| Interferon-alpha | Immune modulation, inhibition of transcription | Pegylated interferon-alpha |
| Experimental entry inhibitors | Attachment & entry via NTCP | Myrcludex B (bulevirtide) |
Exam Tip:
Current approved drugs do not eradicate cccDNA — the reason HBV cannot be completely cured with present therapies.
Transmission
- Parenteral: blood transfusion, needle sharing
- Sexual contact
- Perinatal (mother to child during birth)
Diagnosis
| Marker | Significance |
|---|---|
| HBsAg | Active infection (acute or chronic) |
| Anti-HBs | Immunity (recovery or vaccination) |
| Anti-HBc IgM | Acute/recent infection |
| Anti-HBc IgG | Past infection |
| HBeAg | High infectivity |
| Anti-HBe | Lower infectivity |
| HBV DNA | Quantifies viral replication |
Treatment & Management
- Acute HBV: Supportive care; antivirals only if severe or fulminant hepatitis.
- Chronic HBV: Goal is viral suppression, prevention of cirrhosis/HCC.
- First-line drugs: Tenofovir, Entecavir (potent, low resistance).
- Alternative: Pegylated interferon-alpha (finite duration but more side effects).
- Monitor LFTs, HBV DNA, HBeAg status every 3–6 months.
Prevention: Universal vaccination at birth; HBIG + vaccine for newborns of HBsAg-positive mothers; safe sex and needle practices.
Clinical Case Study: Hepatitis B
Case Presentation:
A 28-year-old male presents with a 2-week history of fatigue, anorexia, nausea, and mild right upper quadrant discomfort. He reports dark urine and yellowing of his eyes for the last 3 days. No significant past medical history. He admits to multiple unprotected sexual encounters in the last 6 months.
- Vitals: T 37.8°C, BP 118/76 mmHg, HR 82 bpm
- Exam: Scleral icterus, mild hepatomegaly, no ascites
- Labs:
- ALT: 1050 U/L
- AST: 950 U/L
- Total bilirubin: 5.6 mg/dL
- HBsAg: Positive
- Anti-HBc IgM: Positive
- HBV DNA: 2 × 107 IU/mL
Interpretation:
Positive HBsAg + Anti-HBc IgM confirms acute hepatitis B infection. Elevated transaminases indicate active hepatocellular injury.
Management Plan:
- Supportive Care: Hydration, rest, avoid alcohol and hepatotoxic drugs (e.g., acetaminophen overdose).
- Monitoring: LFTs every 2–4 weeks, INR, HBV DNA if indicated.
- Antiviral Therapy: Not usually required in immunocompetent adults unless severe/fulminant hepatitis (consider Tenofovir or Entecavir).
- Counseling: Avoid blood/sexual contact until HBsAg negative; test sexual partners and offer HBV vaccination + HBIG if non-immune.
Exam Tip:
In acute HBV, most adults recover completely with supportive care. Chronic infection risk is ~5% in adults but up to 90% in neonates.
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