Hepatitis Viruses Flashcards
1
Q
The human hepatitis virus
A
- 6 known to exist- A, B, C, D, E and G
- not phylogentically related, instead share a common host cell type: hepatocyte
- all cause an initial bout of acute hepatitis on first infection, wide range of severity
- rule out pharmaceutical causes first
- vaccines for A, B, E, desperately need one for C
2
Q
Rule out non-infectious hepatitis
A
- reactions to prescription meds
- med interactions
- acetaminophen OD
- ecstasy
3
Q
Hep A virology
A
- human restricted picornavirus
- fecal-oral transmission, similar replication cycle to other enteroviruses
- if sanitation level is low, contaminated stool reaches drinking water
- highly environmentally stable
- single serotype, no reinfection, vaccine
- neutralizing antibodies recognize virion proteins 1 and 3
4
Q
Hep A Disease
A
- US is a low-endemic area
- CDC rec for routine childhood vaccination in 2006
- viral replication often asymptomatic, but alternatively can keep an adult out of work for a month
- predominantly portal and periportal lymphocytic infiltrate and a varying degree of necrosis
- not very hepatotoxic, symptoms largely immunogenic
- > 99% of patients recover completely: no chronic infection
- rare patients develop fulminant hepatitis- 40% mortality
- risk factors: elderly, preexisting liver disease. Transplant is an option, though most patients eventually recover without
5
Q
Hep A Diagnosis
A
- Enzyme Immunoassay (EIA) for Anti-HepA IgM -> acute infection
- EIA for Anti-Hep A IgG -> past infection, vacccination
- alanine aminotransferase (ALT) level: high-> ongoing liver damage
6
Q
Hep A time course of infection
A
- viraemia- 2-5 weeks after infection
- virus in faeces- 2-7 weeks after infection
- elevated transaminases- 3-9 weeks after infection
- symptoms/jaundice- 4-7 weeks
7
Q
Hep A Treatment
A
-prevention is best: Handwashing, sanitation, water treatment, Hep A vaccine (Twinrix: HAV+HBV)
- prophylaxis is second best: immune serum globulin (Gammagard)
- treatment is symptomatic: best rest, hydration, careful w/ Tylenol
- trace contacts, alert local public health authorities
8
Q
Hep B Virus Virology
A
- human-restricted Hepadnavirus
- small enveloped, DNA virus, partly double stranded
- a very messy virus: 1000X more HBsAg decoys than virions
- unusually stable for an enveloped virus
- only one serotype, HBsAb protective against reinfection -> effective vaccine available
- despite DNA genome, carries a reverse transcriptase and replicates through an RNA intermediate
- replicates in hepatocytes and leaves behind integrated copies of viral DNA
9
Q
Hep B Virus Pathogenesis
A
- transmitted efficiently by injection of contaminated blood, less efficiently by sexual or birth contact
- ~1/3 human pop seropositive worldwide
- in US, 200k new cases annually, 5000 deaths, causes 5-10% of end stage liver failure and 10-15% of hepatocellular carcinoma
- 90% clear the virus
- 10% go fulminant or establish chronic infection
10
Q
Time course of HBV infection
A
- surface antigen appears early, ceases being detectable as surface antibody is produced, resumes being detectable in chronic (incubation period- 1-3 months)
- surface antibody becomes detectable as surface antigen levels fall
- core antibody arises a little later, stays: IgM for acute, IgG for resolved or chronic
- E Antigen detectable when virus most transmissible
11
Q
Four stages of Hep B/ immune interaction
A
1) Immune tolerance- virus replicates w/o symptoms. Lasts 2-4 weeks in adults, decades in newborns. Hep B DNA and antigens in serum, but little antibody
2) Immunogenic symptoms- ALT increases, HepB DNA declines. Coincides w/ 3-4 week symptomatic period (acute) or lasts for years leading to cirrhosis
3) Clearing the virus- viral replication shuts down, HBeAb detected, Hep B DNA not detected, ALT declines, HBsAg remains
4) Virus cleared. No viral antigens, permanent HBsAb IgG
12
Q
Hep B Chronic Infection
A
- ongoing cytotoxic T cell response against infected hepatocytes cause permanent cirrhosis- virus itself is not hepatotoxic
- acculumation of Hep antigen-antibody complexes leads to kidney damage and arthritis (membranous glomerulonephritis, mostly peds)
- virus genome integration, expression of viral transciptional transactivators, and chronic inflammation can lead to cancer (primary hepatocellular carcinoma
13
Q
Hep B Lab Diagnosis
A
- if infection appears active chronic, perform liver biopsy:
- inflammation around portal tracts
- ground glass cytopathology
- positive staining for Hep B antigens
14
Q
Hep B Treatment
A
- Best option: vaccinatin (recombivax, twinrix)- recommended for children and all at risk adults. Recombinant HbsAg produced in yeast- raises neutralizing antibody, blocks virus entry
- second best: antibody prophylaxis (HBIG= HBsAb). Immune globulin administered shortly prior to exposure
- combination of both given for needle sticks and newborns of HBV+ mothers
- provide supportive care for acute hepatitis
- drug treatment for chronic active infection (cure rate is low)- 1 year of polymerase inhibitors and 4 months of PEG-Intron (significantly toxic)- crazy full body alpha interferon
- transplant
- can be sexually transmitted- condoms!
15
Q
Hep C Virus Virology
A
- human-restricted flavivirus: 30-60 nm enveloped +RNA genome
- transmitted by blood, sometimes sex
- discovered in 1989- get blood before that at risk
- ~3 million carriers in US- many unaware
- much high potential for chronic infection, and stronger association with primary hepatocellular carinoma (11-19%)
- no vaccine
