Hepatitis A epidemiology
Fecal-oral transmission
- food workers, poor sanitation, MSM, etc
Rare in developing countries
- passive -> active immunity because endemic
Incubation period = 30 days, can have multiple outbreaks
Hepatitis A virus
Picornavirus (genus hepatovirus)
Hep A presentation
30 day incubation
Nausea, fever, fatigue -> sudden jaundice
Elevated LFTs (AST, ALT, alk phos)
- damage dt lytic release of virions from hepatocytes
- Viremia and excretion precede symptoms!
Jaundice
Excess unconjugated bilirubin
Liver normally: bilirubin-albumin -> bilirubin-glucuronide
Block -> yellow skin, dark urine
Any liver damage (hepatitis, bile blockage, etc) or excess bilirubin production (trauma)
Hep A immunoglobulin
Pooled from general population
Either before or after exposure
Prevents jaundice, etc but still some replication and damage (-> active immunity)
Protection for 4 months
Hep A vaccine
Formaldehyde killed
Recommended for children, travelers, MSM, etc
- can be given up to 2 wks post-exposure!
Hep A diagnosis
Serologic antibody screening
IgM = acute infection (4 months) or recent vaccination
IgG = exposed, either acute or previous
Also use liver function tests
Basic outbreak assessment
Is it just more efficient diagnosis?
Assess for common source
- location
- patient characteristics
- time
Incidence = new cases/time Prevalence = total cases
Hep B structure
Hepadnavirus
Circular DNA - mostly double with two single strand gaps
Virion contains reverse transcriptase (sometimes called “DNA polymerase”)
Icosahedral with envelope
Hep B replication
Entry -> nucleus
Single strand gaps filled in by reverse transcriptase
Host RNA polymerase -> mRNA -> translation
Late -> RNA polymerase -> entire genome RNA (pregenome) -> nucleocapsid -> reverse transcriptase copies to DNA INSIDE NUCLEOCAPSID
-> bud -> enveloped virion
Hep B and C transmission
Blood (transfussion, IV drugs)
Sexual transmission
Perinatal (-> 90% chronic Hep B!)
Longer incubations (B=70days)
Hep B serology
HBsurfaceAg = prevalent in serum if infected ->
HBeAg = internal, replication, correlates to active infection, carcinoma HBcAg = core nucleocapsid, distinguish between immunization and cleared infection
Hep B pathophysiology
Liver damage is from immune response
(CTL -> MHC class I on infected)
Insidious onset of symptoms
- ex AIDS -> less damage -> HAART -> more damage as immune response restored
Chronic Hep B
5% of infections
- > cirrhosis
- > carcinoma
- > infect others
- correlates with E core antigen
Perinatal transmission of Hep B
90% of children become chronic carriers
- 25% die from cirrhosis or carcinoma
- screen in pregnancy -> prevent with double IgG and vaccine
Hep B vaccine
Subunit vaccine (type of killed)
Recombinant particles of surface antigen
(yeast -> purified)
Recommended for infants, etc
Hep B immunoglobulin
Used mostly for perinatal prevention
- also adult post-exposure
General “pooled IgG” doesn’t have enough for B
-> screen for individuals with large amounts of antibody
Post-transfusion hepatitis
Reduced mostly by screening donors Can't: - be hepatitis patient - live with hepatitis patient within 6 months - receive transfusion within 6 months - have + HB-antigen - be paid for donation
Window period: can transmit but can’t be detected
- shorter now due to higher sensitivity of PCR tests
Hepatitis C pathogenesis
Enveloped +RNA virus
Incubation period = 60 days
Hepatocyte damage = immunologically mediated
Most (70-80%) become chronically infected
- continued RNA, symptoms, ALT, etc
- > 20% cirrhosis (more if EtOH)
- > carcinoma -> mortality
Hepatitis B vs C
- long incubation
- acute and chronic
- but Hep C chronic (70-80%)»_space; Hep B (5%)
- cirrhosis and carcinoma
- similar transmission
- prodromal symptoms (arthritis, rash) -> jaundice
Treatment for chronic B or C
Alpha interferon x 4-6 months
- $$, side effects, not super successful
- best in combination with:
B: lamivudine = reverse transcriptase inhibitor
C: ribavirin + protease inhibitor (telaprevir, boceprevir)
Hepatitis tumorigenesis
HBV: 5% chronic -> 2-4% carcinoma
- viral DNA integrated -> oncogene
- also destruction -> regeneration
- immunize!
HCV: 70-80% chronic -> 20% cirrhosis -> carcinoma
- viral DNA does not integrate, no oncogenes
- immune response is tumorigenic
- EtOH increases risk (damage -> regeneration)
Hepatitis D
Circular (-) RNA
Does not make envelope! Must be carried by coinfected Hep B virions
One “delta” protein - diagnosis, antibodies
Always follows Hep B infection -> acute and severe
Hepatitis E
Similar to A (acute onset, fecal oral)
Non-enveloped +RNA
“Hepevirus”
Almost exclusively developing countries
Children = mild, pregnant women -> 20% mortality
