Hepatitis B
Summary
Hepatitis B Virus (HBV) is a DNA virus (Hepadnavirus) that causes acute and chronic liver disease. It is a major global health burden, with >250 million chronic carriers. Transmission is parenteral (blood), sexual, or vertical (mother-to-child). The clinical course depends heavily on the age of acquisition: infants have a 90% risk of chronic infection, whereas adults have a less than 5% risk (95% clear it). Chronic HBV leads to cirrhosis and Hepatocellular Carcinoma (HCC), the latter often occurring even without cirrhosis due to direct oncogenic viral integration. Treatment controls but rarely cures the infection. [1,2]
Key Facts
- DNA Virus: Unlike Hep C (RNA), Hep B integrates into the host hepatocyte nucleus as a stable minichromosome (cccDNA). This makes it incredibly difficult to eradicate.
- Serology (The Golden Rules):
- HBsAg (Surface Antigen) = Infection (Acute or Chronic).
- Anti-HBs (Surface Antibody) = Immunity (Vaccine or Recovery).
- Anti-HBc (Core Antibody) = Exposure (Past or Present). The "Footprint" of the virus.
- HBeAg (E-Antigen): A marker of high viral replication and infectivity. "e = Enormous replication".
- Reactivation: HBV can hide in the liver for decades after "clearance". Immune suppression (especially Rituximab or Chemotherapy) can trigger fatal reactivation.
Clinical Pearls
Vaccine vs Natural Immunity:
- Vaccine: Anti-HBs (+) ONLY. Core antibody (-)
- Natural Immunity: Anti-HBs (+) AND Anti-HBc (+). Think: The vaccine only contains the Surface (S) protein, so you only make anti-S. The virus has a Core, so natural infection makes anti-Core too.
The "Window Period": During acute infection, there is a gap where HBsAg has disappeared but Anti-HBs hasn't appeared yet. The ONLY marker positive is Anti-HBc IgM.
HDV Superinfection: Hepatitis D is a defective virus that needs the Hep B Surface Antigen coat to survive. It cannot exist without Hep B. Co-infection causes rapid, severe fulminant hepatitis.
Transmission
- Vertical: Most common route globally (Asia/Africa).
- Sexual: Unprotected sex.
- Parenteral: IVDU, healthcare exposure.
Chronicity Risk by Age
- Neonates: 90% become chronic.
- Children: 20-50%.
- Adults: less than 5% become chronic (95% clear it symptomatically).
Natural History Phases (EASL)
- HBeAg-positive Infection ("Immune Tolerant"): High DNA, Normal ALT. (Neonates).
- HBeAg-positive Hepatitis ("Immune Clearance"): High DNA, High ALT. Immune system attacks liver.
- HBeAg-negative Infection ("Inactive Carrier"): Low DNA, Normal ALT. Seroconversion (Anti-HBe +ve).
- HBeAg-negative Hepatitis ("Reactivation"): Mutation in pre-core region allows replication without e-Antigen. Fluctuating ALT.
Acute Hepatitis B
Chronic Hepatitis B
- Acute: Tender hepatomegaly. Jaundice.
- Chronic: Often normal. Check for stigamata of CLD (Spider naevi, etc.).
Interpreting Serology (The "Alphabet Soup")
| Marker | Acute Infection | Chronic Infection | Past Infection (Cleared) | Immunised (Vaccine) |
|---|---|---|---|---|
| HBsAg | POSITIVE | POSITIVE (>6m) | Negative | Negative |
| Anti-HBc (IgM) | POSITIVE | Negative | Negative | Negative |
| Anti-HBc (IgG) | Positive | POSITIVE | POSITIVE | Negative |
| Anti-HBs | Negative | Negative | POSITIVE | POSITIVE (>100) |
| HBeAg | Positive | +/- | Negative | Negative |
Other Tests
- HBV DNA (PCR): Viral load (IU/ml). Essential for treatment decisions.
- Liver Function: ALT (reflects immune inflammation).
- Fibrosis Assessment: Fibroscan.
- Delta Screen: Anti-HDV (mandatory in all HBsAg+ patients).
Management Algorithm
HBsAg POSITIVE
↓
CHRONIC or ACUTE? (>6 months)
↓
ASSESS PHASE & LIVER
(DNA, ALT, Fibroscan)
↓
┌─────────┴─────────┐
NO FIBROSIS CIRRHOSIS or
LOW DNA ACTIVE HEPATITIS
NORMAL ALT (High ALT/DNA)
↓ ↓
MONITOR TREATMENT
(6 monthly) (Lifelong)
1. Antiviral Therapy
Goal: Suppression of DNA (not cure). Reduces risk of cirrhosis/HCC.
- Nucleos(t)ide Analogues (NAs): First line. One pill a day.
- Entecavir: Potent, low resistance.
- Tenofovir (TDF or TAF): Potent. Check renal function/bone density with TDF.
- Pegylated Interferon: Finite course (48 weeks). Used in young patients to aim for HBsAg loss. Side effects severe (flu-like, depression).
2. Acute Hepatitis B
- Mostly supportive.
- Treat if: Severe coagulopathy (INR >1.5) or prolonged jaundice.
- Notify: Public Health.
3. Vertical Transmission Prevention
- Universal Screening: All pregnant women screened for HBsAg.
- Neonatal PEP:
- Vaccine: Birth, 4 weeks, 1 year.
- HBIG (Immunoglobulin): Give at birth IF mother is highly infectious (HBeAg+ or high DNA).
- Maternal Therapy: Give Tenofovir to mom in 3rd trimester if Viral Load >200,000 IU/ml.
4. Vaccination
- Recombinant HBsAg.
- Schedule: 0, 1, 6 months.
- Booster: Generally not needed if Anti-HBs >10 (memory cells persist).
- Cirrhosis: Cumulative risk.
- Hepatocellular Carcinoma (HCC): Up to 100x increased risk.
- Polyarteritis Nodosa (PAN): Systemic vasculitis associated with Hep B.
- Membranous Glomerulonephritis: Nephrotic syndrome.
- Acute: >95% adults recover fully.
- Chronic: Tenofovir reduces HCC risk by >50% but does not eliminate it. Life expectacy normal if treated before cirrhosis.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Hepatitis B | EASL / AASLD | Treat all cirrhotics regardless of DNA. Treat chronic hepatitis (High ALT + High DNA). Use Entecavir/Tenofovir. |
| Vaccination | Green Book | Universal Infant Vaccination (UK added to 6-in-1 in 2017). |
Landmark Knowledge
1. The Taiwan Study (Reveille)
- Finding: Risk of HCC correlates linearly with viral load.
- Impact: Established the goal of treatment is maximal viral suppression.
2. cccDNA (The Barrier to Cure)
- HBV DNA forms a "minichromosome" in the nucleus that current drugs cannot destroy. This is why treatment is lifelong (unlike Hep C where the virus stays in cytoplasm).
What is Hep B?
It is a virus that lives in the liver. It is spread through blood (needles) or sex.
Is it curable?
In adults, the body usually fights it off completely within 6 months (Acute). If it stays longer than 6 months (Chronic), we cannot "cure" it (get rid of it completely), but we can control it perfectly with one tablet a day.
The Tablet
You take Tenofovir or Entecavir. It acts like a "handbrake" on the virus, stopping it from copying itself. If you stop the tablet, the virus wakes up and can cause severe liver damage. It is usually for life.
Can I pass it on?
If the tablet works and the virus levels are "undetectable," the risk is extremely low. However, we advise partners to get vaccinated just to be 100% safe. Babies born to positive mothers need a vaccine at birth.
Primary Sources
- European Association for the Study of the Liver (EASL). EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370-398.
- Terrault NA, et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261-283.
- Chen CJ, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65-73.
Common Exam Questions
- Serology Interpretation:
- "HBsAg (+), Anti-HBc IgG (+), HBeAg (-)" -> Chronic Inactive Carrier.
- "HBsAg (-), Anti-HBc IgG (+), Anti-HBs (+)" -> Natural Immunity (Past infection).
- "HBsAg (-), Anti-HBc (-), Anti-HBs (+)" -> Vaccinated.
- Obstetrics: "Management of baby born to HBeAg+ mother?"
- Answer: Vaccine AND Immunoglobulin (HBIG) at birth.
- Oncology: "Patient with past recovered Hep B needs Rituximab. Action?"
- Answer: Prophylactic antiviral (Entecavir) during treatment (high risk of reactivation).
- Pathology: "Histological hallmark?"
- Answer: Ground Glass Hepatocytes.
Viva Points
- HDV: Why is it unique? It is a "satellite" virus. It steals the HBsAg coat to enter cells.
- Mutants: "Pre-core mutant". What is it? A virus that can't make e-Antigen but still replicates. Causes severe "HBeAg-negative Hepatitis" (often fluctuating/aggressive).
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.