Hepatitis - viral
Description
| A | B | C | D | E | |
|---|---|---|---|---|---|
| Genome | ssRNA picornavirus | Partially dsDNA hepadnavirus | ssRNA flavivirus | Defective circular ssRNA | ssRNA hepevirus |
| Route | Faeco-oral | Blood, sexual, perinatal | Blood (PWID) | As HBV | Faeco-oral, zoonotic |
| Incubation | 15-50 d | 60-180 d | 14-160 d | As HBV | 15-60 d |
| Chronic? | Never | Yes (age-dependent) | Yes, ~70% | Yes | Only if immunosuppressed |
| ALF risk | Low (higher if >50 or chronic liver disease) | ~1% | Lowest | Highest | ~20% in 3rd-trimester pregnancy |
| Vaccine | Yes | Yes | No | Via HBV vaccine | Yes (China only) |
| Treatment | Supportive | NA, indefinite | DAA, curative | Bulevirtide | Ribavirin if chronic |
- Mnemonic: the vowels (A and E) go through the bowels; B, C and D are blood-borne
- HCV: least likely to cause acute liver failure, most likely to become chronic
- **A defective virus: HDV needs HBsAg for its envelope - it cannot replicate or cause disease without HBV**
Epidemiology
- Hepatitis E is the commonest cause of acute hepatitis worldwide
- The leading cause of acute liver failure in Central Asia, with particularly high mortality in pregnant women
- Genotypes 1/2 - human, waterborne outbreaks (Asia, Africa). Genotypes 3/4 - zoonotic, sporadic, developed countries incl. Australia
- HAV: falling in Australia with vaccination; outbreaks in MSM, PWID, returned travellers, imported frozen berries
- HBV ~220,000 Australians; HCV ~120,000
- HDV in ~5% of HBsAg-positive people globally; higher in Central Asia, Mongolia, West Africa, parts of Eastern Europe
Aetiopathogenesis
Transmission
- HAV - faeco-oral, contaminated food/water, shellfish, MSM sexual transmission; most infectious in the 2 weeks BEFORE jaundice
- HBV - parenteral, sexual, perinatal (dominant in high-prevalence settings)
- HCV - blood; PWID 80-90% of Australian cases
- HDV - as HBV. Coinfection (simultaneous with HBV) vs superinfection (onto established chronic HBV)
- HEV - faecally contaminated drinking water, contaminated milk from infected cows, undercooked pork products, and rarely blood products; also transfusion and transplant transmission
HDV mechanism
- Defective virus - requires HBV surface antigen for its envelope, so it can only infect HBsAg-positive people
- Superinfection -> ~80% chronicity and rapid progression; coinfection -> usually self-limits (~5% chronicity) but higher ALF risk
- HDV suppresses HBV replication -> low HBV DNA with high ALT should prompt HDV testing
Why some become chronic
- Age at HBV infection is the dominant determinant (immature immune response -> tolerance)
- HCV quasispecies diversity + weak CD4/CD8 response -> escape
- IL28B (IFNL3) genotype predicts spontaneous HCV clearance
Diagnosis
Serology - which test answers which question
| Question | Test |
|---|---|
| Acute HAV | anti-HAV IgM (IgG = immunity, vaccine or past) |
| Acute HBV | HBsAg + IgM anti-HBc |
| Chronic HBV | HBsAg >6 months; HBV DNA quantifies |
| HCV exposure | anti-HCV (window ~6 weeks) |
| Active HCV | HCV RNA |
| HDV | anti-HDV, then HDV RNA |
| Acute HEV | anti-HEV IgM; HEV RNA if immunosuppressed (serology unreliable) |
HDV testing
- HDV antigen can be lost soon after acute infection - test HDV RNA (viral load) if suspicion persists
- Test every HBsAg-positive person at least once. Prioritise: HCV or HIV coinfection, PWID, MSM, other STI risk, birth in a high-endemicity region, and unexplained low HBV DNA with high ALT
Clinical patterns
- Acute HAV: abdominal pain and diarrhoea prominent
- Acute HBV: non-specific - anorexia, malaise, jaundice; serum-sickness prodrome (arthralgia, urticaria) in ~10-20%
- Acute HCV: mild or insidious, usually asymptomatic
- Any: ALT typically in the thousands, bilirubin rises after ALT peaks
In any acute hepatitis
- INR and encephalopathy assessment - these define acute liver failure, not the ALT height
- Full viral panel + EBV, CMV, HSV; autoimmune screen; caeruloplasmin if <40; paracetamol level; drug and herbal history; hepatic vein Doppler
Management
Hepatitis A
- Supportive. No antiviral
- Notifiable; exclude from food handling, childcare and healthcare until 7 days after jaundice onset
- Post-exposure prophylaxis within 14 days: HAV vaccine for healthy people 1-40 years; normal human immunoglobulin for age <1 or >40, immunocompromised, or chronic liver disease
- Vaccinate: travellers to endemic areas, MSM, PWID, chronic liver disease, occupational risk, Aboriginal and Torres Strait Islander children in high-risk regions
Hepatitis B
- Acute: supportive; antivirals only for severe/protracted disease or ALF; <5% of adults become chronic
- Chronic: entecavir, tenofovir disoproxil or tenofovir alafenamide - indefinite, suppressive not curative
- Post-exposure: HBIG + vaccine (non-immune); newborn of an HBsAg-positive mother: HBIG + birth-dose vaccine within 12 hours
- Universal infant vaccination in Australia since 2000
Hepatitis C
- Pan-genotypic DAA, curative in >95%: sofosbuvir/velpatasvir 12 weeks or glecaprevir/pibrentasvir 8 weeks
- Treat everyone, regardless of fibrosis or ongoing drug use; GP-prescribable in Australia
- No vaccine and no post-exposure prophylaxis - monitor RNA after exposure and treat if it becomes positive
Hepatitis D
Verified 2026: bulevirtide received FDA accelerated approval in May 2026 - the first approved therapy for chronic HDV. Older teaching that "there is no treatment beyond pegylated interferon" is out of date.
- Bulevirtide 8.5 mg subcutaneously daily - an entry inhibitor blocking HBsAg-enveloped particles from binding NTCP, the cell-entry receptor for HBV and HDV
- For chronic HDV without cirrhosis or with compensated cirrhosis
- MYR301: combined HDV RNA suppression + ALT normalisation 48% vs 2% at week 48; undetectable HDV RNA rising to 50% by week 144
- Boxed warning: severe acute exacerbation of hepatitis after stopping - anticipate multi-year therapy
- Pegylated interferon alfa - limited efficacy, poor tolerance
- Nucleos(t)ide analogues do not treat HDV (they suppress HBV DNA only) - continue if HBV needs treatment
- Transplantation for decompensated disease
- Prevention is the HBV vaccine - it prevents HDV as well
Hepatitis E
- Supportive in immunocompetent people
- Chronic HEV in the immunosuppressed (transplant, HIV, haematological malignancy) -> reduce immunosuppression first; then ribavirin
- Ribavirin is teratogenic - avoid in pregnancy despite the high mortality
- Prevention: safe water, cook pork thoroughly, avoid undercooked game/offal
All acute viral hepatitis
- Notifiable to public health; contact tracing
- Avoid alcohol and hepatotoxic drugs; check paracetamol dosing
- Monitor INR and mental state for progression to acute liver failure -> transplant centre
Associations
- HBV - polyarteritis nodosa, membranous GN, MPGN, Guillain-Barre, papular acrodermatitis (Gianotti-Crosti)
- HCV - mixed cryoglobulinaemia, MPGN, porphyria cutanea tarda, lichen planus, sicca, B-cell NHL, T2DM
- HAV - cholestatic hepatitis, relapsing hepatitis, autoimmune hepatitis trigger; rarely GBS
- HEV - neurological: Guillain-Barre, neuralgic amyotrophy (Parsonage-Turner), encephalitis; also glomerulonephritis, pancreatitis, aplastic anaemia
- HDV - the fastest-progressing chronic viral hepatitis
- HIV coinfection accelerates all of them
Natural history & complications
Chronicity
- HAV: never chronic (but relapsing and cholestatic variants occur over months)
- HBV: ~90% neonatal, 20-30% age 1-5, <5% adult
- HCV: ~65-75% chronic (25-35% clear spontaneously)
- HDV: superinfection ~80% chronic; coinfection ~5%
- HEV: only in the immunosuppressed
Acute liver failure risk
- HDV coinfection highest; HBV ~1%; HEV ~20% mortality in third-trimester pregnancy
- HAV: ALF rare, but risk rises with age >50 and with pre-existing chronic liver disease - hence vaccinating all patients with chronic liver disease
- HCV: essentially never
Long-term
- HBV -> cirrhosis and HCC, including without cirrhosis (~20%)
- HCV -> cirrhosis at ~20 years, HCC at ~30, almost always on a cirrhotic background
- HDV -> cirrhosis in ~70% within 5-10 years; the highest HCC risk of the hepatitides
- Chronic HEV in transplant recipients -> rapid cirrhosis
Monitor
- Acute: LFT, INR, mental state until resolving; confirm HBsAg clearance at 6 months
- Chronic: as per the individual HBV/HCV notes; HDV RNA and ALT on bulevirtide
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