Microbiology chapters
Viral hepatitis
The five hepatitis viruses compared (A, B, C, D and E): how each spreads, incubation, chronicity, mortality and prevention, with a step-by-step guide to hepatitis B antigens and antibodies (HBsAg, HBeAg, anti-HBc IgM, anti-HBs), the window period, carriers, mother-to-child transmission and hepatitis C testing in Pakistan.
- Hepatitis A and E are faecal-oral (contaminated water and food), never chronic; E causes water-borne epidemics and high mortality in pregnancy (third trimester); hepatitis B, C and D spread by blood (unsafe injections, reused syringes, transfusions, dental and surgical instruments, razors), sex and mother to child, and can become chronic → cirrhosis and hepatocellular carcinoma; D is a defective virus that needs HBsAg to replicate.
- Hepatitis B markers: HBsAg (infection, acute or chronic; >6 months = chronic), HBeAg and HBV DNA (active replication, high infectivity), anti-HBc IgM (acute infection; the only marker in the window period), anti-HBc IgG (past or ongoing infection), anti-HBs (recovery or vaccination: immunity; vaccinated people have anti-HBs only); the risk of chronicity is about 90% after perinatal infection but under 5% in adults.
- Hepatitis C becomes chronic in most people (often silent), is common in Pakistan from unsafe injections, is screened with anti-HCV and confirmed by HCV RNA PCR, and is curable with direct-acting antivirals (sofosbuvir-based, 12 weeks); there is no vaccine for C; hepatitis B vaccine (birth dose + EPI) also prevents D.
On this page
Comparison of hepatitis viruses
| Feature | A | B | C | D | E |
|---|---|---|---|---|---|
| Family | Picornavirus (hepatovirus) | Hepadnavirus | Flavivirus | Deltavirus (defective) | Hepevirus |
| Genome | ssRNA (+) | Partly double-stranded DNA (uses reverse transcriptase) | ssRNA (+) | ssRNA (circular, −) | ssRNA (+) |
| Envelope | No | Yes | Yes | Yes (HBsAg coat) | No |
| Transmission | Faecal-oral (water, food, shellfish) | Blood, sexual, perinatal | Blood (unsafe injections, transfusion, IV drugs); sexual and perinatal less often | Blood, sexual (needs HBV) | Faecal-oral (water-borne epidemics) |
| Incubation | About 2–6 weeks | About 1–6 months | About 2–26 weeks | Similar to B | About 2–8 weeks |
| Chronic infection | Never | Yes (age-dependent) | Yes (most infected adults) | Yes (especially superinfection) | No (except immunosuppressed) |
| Carrier state | No | Yes | Yes | Yes | No |
| Fulminant hepatitis | Rare | Uncommon | Rare | More common (superinfection) | High in pregnancy (third trimester) |
| Liver cancer | No | Yes | Yes | Yes (via B) | No |
| Vaccine | Yes (inactivated) | Yes (recombinant HBsAg) | No | HBV vaccine protects | Yes (China only) |
| Diagnosis | Anti-HAV IgM | HBsAg, anti-HBc IgM, etc. | Anti-HCV, HCV RNA | Anti-HDV, HDV RNA | Anti-HEV IgM |
"The vowels (A, E) hit your bowels": A and E are faecal-oral and not chronic. B, C and D spread through blood and body fluids and can be chronic.
Clinical features of acute hepatitis (all types): prodrome (fever, anorexia, nausea, fatigue, right upper quadrant discomfort, aversion to smoking), then jaundice, dark urine, pale stools, tender liver; ALT greatly raised (hundreds to thousands). Many infections (especially in children and hepatitis C) are anicteric or silent.
Hepatitis A
- Common in childhood in countries with poor sanitation (mild in children, more severe in adults); outbreaks from contaminated water and food.
- Virus shed in stool for about 2 weeks before jaundice (most infectious time).
- No chronic infection; lifelong immunity; fulminant disease rare (older adults, existing liver disease).
- Diagnosis: anti-HAV IgM (acute); anti-HAV IgG = past infection or vaccination.
- Prevention: sanitation, safe water, handwashing; inactivated vaccine; immunoglobulin for contacts.
Hepatitis B
The virus
- Hepadnavirus: small, enveloped, partly double-stranded circular DNA; replicates through an RNA intermediate using reverse transcriptase (so drugs like tenofovir and entecavir work); can integrate into host DNA (cancer risk).
- Dane particle = complete infectious virion (42 nm).
- Large excess of non-infectious HBsAg particles (spheres and filaments) circulate in blood.
- Not cytopathic: liver damage is caused by the immune response (CD8 T cells).
- Very infectious: far more infectious than HIV after needlestick exposure; survives on surfaces for days.
Antigens and antibodies
| Marker | Meaning |
|---|---|
| HBsAg (surface antigen, "Australia antigen") | Current infection (acute or chronic); first marker to appear (before symptoms). Present more than 6 months = chronic infection |
| Anti-HBs | Immunity: after recovery or vaccination; protective (level above 10 mIU/mL) |
| HBcAg (core antigen) | Found in liver cells, not in serum |
| Anti-HBc IgM | Acute (recent) infection; the only marker in the window period |
| Anti-HBc IgG (total anti-HBc) | Past or chronic infection (stays for life); not produced by vaccination |
| HBeAg | Active viral replication and high infectivity; mothers who are HBeAg positive transmit to most babies without prophylaxis |
| Anti-HBe | Lower replication and infectivity (seroconversion); some precore mutants still replicate |
| HBV DNA (PCR) | Viral load: replication, need for treatment, response to therapy |
Window period: after HBsAg disappears and before anti-HBs is detectable; only anti-HBc IgM is positive. A blood donor screened only for HBsAg can transmit infection during this time.
Interpreting hepatitis B serology
| HBsAg | Anti-HBc (total) | Anti-HBc IgM | Anti-HBs | HBeAg | Interpretation |
|---|---|---|---|---|---|
| − | − | − | − | − | Susceptible (never infected, not vaccinated): vaccinate |
| − | − | − | + | − | Immune from vaccination |
| − | + | − | + | − | Immune from past infection (recovered) |
| + | + | + | − | + | Acute infection (highly infectious) |
| − | + | + | − | − | Window period (acute, resolving) |
| + | + | − | − | + or − | Chronic infection (HBeAg + = high infectivity) |
| − | + | − | − | − | Isolated anti-HBc: past infection with low anti-HBs, occult infection or false positive |
Vaccinated = anti-HBs alone. Recovered = anti-HBs + anti-HBc IgG. Acute = HBsAg + anti-HBc IgM. Chronic = HBsAg for more than 6 months + anti-HBc IgG.
Course and outcome
- Risk of chronic infection depends on age at infection: about 90% of infected newborns, roughly 25–50% of children aged 1–5, and under 5% of healthy adults. This is why the birth dose matters.
- Chronic hepatitis B → cirrhosis, hepatocellular carcinoma (can arise even without cirrhosis, because the DNA integrates), liver failure.
- Extrahepatic: polyarteritis nodosa, membranous glomerulonephritis, serum sickness-like illness.
- Acute infection in adults: most recover; fulminant hepatitis in a small minority.
Prevention
- Hepatitis B vaccine: recombinant HBsAg (made in yeast); birth dose within 24 hours, then in the pentavalent vaccine at 6, 10 and 14 weeks (Pakistan EPI); adults: 0, 1 and 6 months (health workers should check anti-HBs after the course).
- Babies of HBsAg-positive mothers: vaccine + hepatitis B immunoglobulin (HBIG) within 12 hours of birth (prevents most transmission); antivirals (tenofovir) in the third trimester for mothers with high viral loads.
- Needlestick injury: check the source and the worker's immunity; give HBIG + vaccine to the unvaccinated or non-responders.
- Safe injections (auto-disable syringes), screened blood, sterilised instruments, safe sex.
- Treatment of chronic infection: tenofovir or entecavir (long-term suppression); peginterferon in selected cases.
Hepatitis C
- Flavivirus, enveloped + RNA; high mutation rate (quasispecies), so no vaccine and reinfection is possible. Genotype 3 is the most common in Pakistan.
- Transmission: blood: unsafe injections and reused syringes (a major driver in Pakistan), unscreened transfusions, dialysis, dental and surgical procedures, barbers' razors, tattoos, IV drug use; sexual and vertical transmission are less common.
- Acute infection is usually silent; most infected adults (roughly 70–85%) develop chronic infection; about a fifth to a quarter of these develop cirrhosis over 20–30 years; then hepatocellular carcinoma risk.
- Extrahepatic: mixed cryoglobulinaemia, membranoproliferative glomerulonephritis, porphyria cutanea tarda, lichen planus, insulin resistance.
- Diagnosis: anti-HCV antibody (screening; positive after past or current infection) → HCV RNA PCR (confirms active infection; viral load); genotype if needed. Anti-HCV may be negative early and in immunosuppressed patients.
- Treatment: direct-acting antivirals such as sofosbuvir + daclatasvir or sofosbuvir + velpatasvir for 12 weeks (cure rates above 90%); confirm cure by undetectable HCV RNA 12 weeks after treatment (sustained virological response).
- Pakistan has one of the highest hepatitis C burdens in the world and national programmes aiming at elimination through screening and treatment.
Hepatitis D (delta)
- Defective RNA virus: needs HBsAg for its coat, so it only infects people with hepatitis B.
- Coinfection (HBV and HDV at the same time): acute hepatitis, more severe, but usually clears (like acute B).
- Superinfection (HDV in a chronic HBV carrier): severe, often fulminant, high risk of chronic infection and rapid cirrhosis.
- Diagnosis: anti-HDV antibody, HDV RNA. Prevented by hepatitis B vaccination.
Hepatitis E
- Non-enveloped + RNA virus; faecal-oral, especially contaminated drinking water; large epidemics after floods and in the monsoon (outbreaks have occurred in Pakistan); genotypes 3 and 4 also come from pork and game.
- Usually self-limiting; no chronic infection (except in transplant and immunosuppressed patients).
- Pregnant women (especially the third trimester) can develop fulminant hepatic failure with high mortality (often quoted as up to about 20–25%), plus fetal loss.
- Diagnosis: anti-HEV IgM, HEV RNA.
- Prevention: safe water and sanitation.
Infectivity and mortality in brief
- Most infectious after needlestick: HBV (especially HBeAg positive) far exceeds HCV, which exceeds HIV.
- Highest chronicity: HCV in adults; HBV in neonates.
- Highest fulminant mortality: HEV in pregnancy; HDV superinfection.
- Liver cancer risk: HBV, HCV (and HDV through HBV).
Suppose 1,000 people are infected at each age:
Newborns: about 90% → 0.9 × 1,000 = 900 become chronic carriers
Children aged 1–5: about 30% (range 25–50%) → 0.3 × 1,000 = 300
Adults: about 5% or less → 0.05 × 1,000 = 50
Infection at birth gives about 900 ÷ 50 = 18 times more carriers than adult infection
→ birth dose vaccine within 24 hours (+ HBIG if the mother is positive)
Expect: comparison of A–E (family, genome, route, chronicity, vaccine), faecal-oral vs blood-borne, hepatitis B virus features (DNA, reverse transcriptase, Dane particle), meaning of each HBV marker (HBsAg, anti-HBs, anti-HBc IgM and IgG, HBeAg, HBV DNA), the window period, serology patterns (vaccinated, recovered, acute, chronic), age and chronicity, birth dose and HBIG, needlestick management, hepatitis C transmission in Pakistan, anti-HCV vs PCR, DAA treatment, HDV coinfection vs superinfection, HEV in pregnancy.
Quick revision
- A and E: faecal-oral, not chronic; E dangerous in pregnancy.
- B, C, D: blood, sex, perinatal; chronic; cirrhosis and HCC.
- HBV: DNA, reverse transcriptase; HBsAg first; HBeAg = high infectivity; anti-HBc IgM = acute and window period; anti-HBs = immunity.
- Vaccinated: anti-HBs only. Recovered: anti-HBs + anti-HBc IgG.
- Chronicity: 90% newborns, < 5% adults.
- HCV: RNA flavivirus; unsafe injections; most become chronic; anti-HCV then PCR; DAAs cure.
- HDV: needs HBsAg; superinfection severe.
Written by The House Job from standard microbiology references (Levinson's Review of Medical Microbiology and Immunology).
FAQ
Which hepatitis B marker is present in the window period?
Anti-HBc IgM, when HBsAg has disappeared and anti-HBs has not yet appeared.
What does HBeAg indicate?
Active replication of hepatitis B virus and high infectivity.
Which serological profile shows immunity from vaccination?
Anti-HBs positive with negative HBsAg and negative anti-HBc.
Why is hepatitis E dangerous in pregnancy?
Pregnant women, especially in the third trimester, can develop fulminant liver failure with high mortality.