Hepatitis

Question 1

Hepatitis A epidemiology

Answer 1

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

Question 2

Hepatitis A virus

Answer 2

Picornavirus (genus hepatovirus)

Question 3

Hep A presentation

Answer 3

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!

Question 4

Jaundice

Answer 4

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)

Question 5

Hep A immunoglobulin

Answer 5

Pooled from general population
Either before or after exposure
Prevents jaundice, etc but still some replication and damage (-> active immunity)
Protection for 4 months

Question 6

Hep A vaccine

Answer 6

Formaldehyde killed
Recommended for children, travelers, MSM, etc

• can be given up to 2 wks post-exposure!

Question 7

Hep A diagnosis

Answer 7

Serologic antibody screening
IgM = acute infection (4 months) or recent vaccination
IgG = exposed, either acute or previous

Also use liver function tests

Question 8

Basic outbreak assessment

Answer 8

Is it just more efficient diagnosis?

Assess for common source

• location
• patient characteristics
• time

Incidence = new cases/time
Prevalence = total cases

Question 9

Hep B structure

Answer 9

Hepadnavirus
Circular DNA - mostly double with two single strand gaps
Virion contains reverse transcriptase (sometimes called “DNA polymerase”)
Icosahedral with envelope

Question 10

Hep B replication

Answer 10

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

Question 11

Hep B and C transmission

Answer 11

Blood (transfussion, IV drugs)
Sexual transmission
Perinatal (-> 90% chronic Hep B!)

Longer incubations (B=70days)

Question 12

Hep B serology

Answer 12

HBsurfaceAg = prevalent in serum if infected ->

HBeAg = internal, replication, correlates to active infection, carcinoma
HBcAg = core nucleocapsid, distinguish between immunization  and cleared infection

Question 13

Hep B pathophysiology

Answer 13

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

Question 14

Chronic Hep B

Answer 14

5% of infections

• > cirrhosis
• > carcinoma
• > infect others
• correlates with E core antigen

Question 15

Perinatal transmission of Hep B

Answer 15

90% of children become chronic carriers
- 25% die from cirrhosis or carcinoma

• screen in pregnancy -> prevent with double IgG and vaccine

Question 16

Hep B vaccine

Answer 16

Subunit vaccine (type of killed)
Recombinant particles of surface antigen
(yeast -> purified)
Recommended for infants, etc

Question 17

Hep B immunoglobulin

Answer 17

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

Question 18

Post-transfusion hepatitis

Answer 18

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

Question 19

Hepatitis C pathogenesis

Answer 19

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

Question 20

Hepatitis B vs C

Answer 20

• long incubation
• acute and chronic
• but Hep C chronic (70-80%)&raquo_space; Hep B (5%)
• cirrhosis and carcinoma
• similar transmission
• prodromal symptoms (arthritis, rash) -> jaundice

Question 21

Treatment for chronic B or C

Answer 21

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)

Question 22

Hepatitis tumorigenesis

Answer 22

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)

Question 23

Hepatitis D

Answer 23

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

Question 24

Hepatitis E

Answer 24

Similar to A (acute onset, fecal oral)
Non-enveloped +RNA
“Hepevirus”

Almost exclusively developing countries
Children = mild, pregnant women -> 20% mortality