Gi System- Hepatitis Abcde By Blue

Front 1

GI System- Hepatitis ABCDE by Blue

Back 1

GI System- Hepatitis ABCDE by Blue

Front 2

Infectious vs Serum Hepatitis

Back 2

Infectious (A)- traditional passing from person-person/ fecal-oral spread

serum (B,D)- spread through blood

B,C,D- chronic infection

Front 3

Hepatitis A Virus (infectious hepatitis)

Back 3

Picornavirus, aka enterovirus 72, subgroup hepatovirus.
Single serotype (infection/recovery = lifetime immunity--> only get it once!).
Acid stable.

Disease characteristics:
Incubation period 15-45 days (long); long infectability
Pre-icteric (gastroenteritis, transmission) and icteric (jaundice) phase.

Pathogenesis:
ingestion of infected material-> absorption from stomach or small intestine -> replication in liver -> secretion into bile -> excretion in stool or reabsorption

Front 4

Hepatitis, adults and children. jaundice, infection, rash, mortality

Back 4

Jaundice (hepatitis) more prevalent in adults (70%) than children (7% ages 1-5; 37% ages 5-9).

Infection more prevalent in children; asymptomatic, milder GI-illness w/o jaundice. Source of spread to adults (& therefore vaccine target).

Rash may occur (fever/rash diarrhea in children).

Mortality rate relatively low, <1%. No chronicity. 2nd attacks unknown.

*you don't see liver/ hepatitis symptoms until you see immune response. the damage comes from the immune response.

Front 5

Concentration of Hepatitis A Virus in Various Body Fluids

Back 5

Transmitted by fecal-oral route (person-person), food (esp. shellfish), water. Infected individuals can shed virus for 2 weeks -12 months.

B. Small epidemics or clusters due to contamination of food by food handlers.

C. Most common in children (asymptomatically).

Front 6

Treatment and Prevention

Back 6

A. No antivirals.

B. Inactivated vaccines available (HAVRIX, VAQTA). Recommended in U.S.(childhood)
+ international travel to endemic areas.
Passive immunization (Gammagard).

Front 7

Hepatitis B virus (serum hepatitis)

Back 7

Genotypes A-G.

HBV, Dane particle, dsDNA genome, reverse transcription

Hbs-antigen, hepatitis B surface antigen, aka “Australia” antigen is outer capsid. Appears in large quantities in blood. (the virus produces far more surface protein outer shell than it needs, so the excess goes into the bloodstream)

HBc-antigen is inner capsid. Not detectable in blood

HBe antigen is non-structural, but detectable in blood.

Hbx gene - inhibitor of p53; also inhibits GSK-3b tumor suppressor. May promote oncogene activation.

Front 8

Disease Characteristics of Hep B

Back 8

Pre-icteric and icteric phases. Hepatic lesions. Immunopathogenic,
inflammatory mechanism. Asymptomatics common.

Incubation period long, 30-180 days.

Mortality rate higher, including acute fulminant, persistence leading
to cirrhosis, hepatocellular carcinoma. Influence of age.
(the younger you are, the less likely there's going to be initial primary disease. the younger you are, the more likely you will develop chronic disease)

More severe than type A.
Recovery prolonged. Carrier state/chronicity can develop:

Front 9

HBV outcomes for adults:

Back 9

After infection:

Weak response:
24% recovery/immunity
1% death

Strong response:
65% recovery/ immunity

10% chronic -> cirrhosis, PHC, death

Front 10

Acute Hepatitis B Virus: Infection with Recovery, Typical Serological Course

Back 10

After about 4 week incubation, the HBsAg and HBeAg will be positive for a period of time until there is sufficient immune response (both were + in blood samples).

IgM Antibodies for HBe HBc are made.
very delayed response to HBs antigen

Front 11

Progression to Chronic Hepatitis B Virus Infection
Typical Serologic Course

Back 11

anti-HBe is delayed for well over a year, and there's no response to HBs

Front 12

Epidemiology

Back 12

Global - 350,000,000 carriers worldwide

Transmitted by blood products, infected needles, syringes, sexually. Same as HIV.

Occurs in sporadic cases throughout the year.

Most common in adults due to nature of transmission.

Perinatal transmission results in chronic HBV in 90%.

Front 13

Prevention and Treatment.

Back 13

Subunit vaccines available (Energix-B, Recombivax HB). Cloned Hbs gene. Health care workers, all newborns, children.

Licensed in 1982; currently recombinant (in US)

Routine infant: 3 dose series, typical schedule 0, 1-2, 4-6 months. (Infants born to HBV-infected mothers should be given HBIG and vaccine within 12 hours of birth.)

Ages 11-15 “catch up”, and through age 18: 2/3 dose series (adult dose);

Over 18 – high risk: Occupational risk (HCWs); Hemodyalisis patients; All STD clinic clients; Multiple sex partners or prior STD; Inmates in correctional settings; MSM; IDU; Institutionalized for developmental disability. 3 dose series.

(TwinRix: combination killed HAV/recombinant HBV.)

Protection ~30-50% dose 1; 75% - 2; 96% - 3; lower in older, immunosuppressive illnesses (e.g., HIV, chronic liver diseases, diabetes), obese, smokers.

Interferon alpha (side effects); Nucleotide analogues (RTI’s): lamivudine, adefovir, entecavir, telbivudine (2006). Combination.

Front 14

Delta hepatitis virus (hepatitis D virus).

Back 14

Defective, satellite virus/viroid that uses outer coat protein of HBV as capsid.

Increases severity of HBV infection, and likelihood of fulminant hepatitis, chronicity.

Acquired by co-infection or super-infection.

RNA genome is a ribozyme (similarity to plant viroids, virusoids).

Front 15

Hepatitis C virus: the major problem in the US. pathogenesis

Back 15

Flavivirus, 6 genotypes, 3 in U.S.
High replication rate: 10 billion new viral particles/day
Widespread liver infection: up to 50% of hepatocytes in those w/chronic infection.
High mutation rate: “quasispecies”, mutant swarm
Six genotypes – variable response to antiviral treatment
Transmission – IV drug abuse, sexual, alcohol abuse

80% infected will have a long term infection
no vaccine (mutation problem)

Front 16

If the ELISA test is negative, you can stop there, but if it's positive, what do you have to do next?

Back 16

there's a lot of false positives, so you have to do a RIBA immunoblot essay and a PCR testing for positives. if those are negative, than the ELISA was a false positive.

Front 17

Hep E, Hep G

Back 17

Hepatitis E found primarily in developing countries. Leading worldwide cause of *waterborne hepatitis. Disease and transmission similar to Hepatitis A. Vaccine in clinical trials.
*high death rate if acquired during pregnancy

Hepatitis G virus (aka GB virus-C) discovered in 1995.
Flavivirus, related to Hepatitis C virus. Recently questioned as causative agent. TTV.