viral hepatitis Flashcards
hepatitis A
What virus causes? What is the epidemiology of? What is the incubation period? Is viremia present? Why is it rare in developing countries?
picornavirus in genus hepatovirus
epidemiology like that of polio
overt disease rare in low sanitary conditions because infection of infants results in passive–> active immunity without disease
30 day incubation period
fecal excretion of virus takes several weeks, viremia takes about a week
viremia infects liver
rare in developing countries because the virus is prevalent in these countries and there is passive immunity from mother coupled with secondary active immunity from exposure
hepatitis A - pathogenesis
When does viremia occur?
What are symptoms?
after about 1 week, viremia results in infection in liver
viral growth in liver cells results in anorexia, nausea, fever, and jaundice because of deposition of bilirubin in skin
abnormal liver function tests (LFTs)
damage in liver due to lysis of infected cells to release progeny virions
common causes of focal epidemics (5) for Hepatitis A
common causes as in social situations that benefit virus communication
1: outdoor summer events with inadequate sanitary facilities
2: from raw or inadequately cooked shellfish contaminated by sewage
3: within one family (spread by children’s fecal contamination)
4: from infected food handler in USA
5: from fecally contaminated food, usually imported
pooled gamma globulin for Hep A
How long is this effective?
How effective is it?
used to use intermuscluarly injected pooled human gamma globulin to protect travelers to areas when hep A is epidemic
vaccine now available so this is used primarily after suspected exposure
passive immunity does the following:
1: prevents jaundice and malaise after infection
2: doesn’t completely prevent liver damage - elevated liver tests still occur
3: provides protection for about 4 months
heme excretion
(pathway and jaundice)
1: old RBC (heme) converted to bilirubin in spleen
2: transported as bilirubin-albumin complex in the blood
3: converted to bilirubin-glucuronide in liver
4: excreted in bile as the above complex
5: excreted in feces as bilirubin metabolites - feces brown because of bilirubin
with viral hepatitis, step 3 is blocked so there’s a buildup of bilirubin-albumin => jaundice = yellowed skin, dark urine because excreted through urine, pale feces
Hep A vaccine
Is it killed or live?
Who is recommended to receive the vaccine?
formaldehyde-killed
recommended for all children, travelers to highly epidemic areas, men who have sex with men, persons who regularly receive blood products, adults in states with history of elevated rates of infection, and people with chronic liver disease
testing for Hep A
Explain how to test for Hep A. What are do positive and negative results mean from (two specific Ig-type tests)
can be cultured in lab but procedure not generally available
use serological test for antibody to virus
look for anti-HAV-IgG and anti-HAV-IgM
if negative for both antibodies, disease not Hep A
if negative for IgM but positive for IgG, has had hepA in the past or has had the vaccine but that’s not the current ailment
if positive for both antibodies, has acute infection or recent vaccination
how to study epidemiology of acute infection
1: ensure that it’s epidemic and not just better detection of disease
2: plot cases on map, looking for clustering that could suggest pattern of transmission
3: compare types of people infected to look for mode of exposure (occupation, age, food consumption, etc.)
4: plot timeline of appearance of new cases, looking for incidence and prevalence - in simple epidemics all individuals clustered around the incubation period
prevalance
What does this term mean?
How does it compare with “incidence”?
total number of cases (expressed per 100/1000/10000 individuals)
so if we were to come up with a vaccine for AIDS tomorrow, the prevalence of AIDS wouldn’t change, because the same number of people will still be infected, but the incidence will
common-source epidemic
What does this term mean?
simplest type of epidemic
all individuals are infected at roughly the same time and new cases are clustered around the incubation period (so get very pointy bell curve when you plot incidence and time)
hepatitis B virus
What type of virus is this?
What type of nucleotide does it have?
What special replication machinery does it have?
hepadnavirus
virion has circular DNA that is mostly double stranded but has some single-stranded regions
contains enzyme for replication of its genome - often called DNA polymerase but is actually a reverse transcriptase
has lipoprotein envelope with viral glycoproteins as outer layer
unique because translates from RNA to DNA - has reverse transcriptase (Pol protein)
sloppy replication - get over production of virions but that don’t have viral genome so not infectious - not clear why this happens, but might be to confuse immune system by having too many targets - useful as diagnostic test - virus can suppress antibody response against it
hep B disease
What is the incubation period?
What happens to the liver of acute and chronic carriers?
incubation period about 70 days
hepatocytes damaged by immune system
chronic carriers have chronic hepatitis and primary liver carcinoma
transmission of Hep B
What are modes of transmission of?
1: blood transfer with infected blood
2: sexual transmission
3: perinatal infection of neonates by their mothers
4: sharing needles
tests for Hep B
What are the tests?
serological tests for virus and antibody
hep B antigens (HB-Ags) will be present
Hep B antigens (HB-Ags)
What percentage of patients have Ags for life?
complex mixture of virions and subviral particles
divided into two groups depending on location in virions - core (nucleocaspid) or surface (envelope glycoproteins)
Ag usually only seen in serum for several weeks after infection, but about 5% of patients get chronic infection so Ag persists for years or for life
HBeAg
Is this a core or envelope antigen?
Is it indicative of any particular illness?
Are Abs present? In which patients?
Hep B antigen - circulating core antigen e
strongly correlated with presence of infectious HBV and with progression to carcinoma in chronically infected patients
antibodies to HBeAg (and HBsAg) are usually suppressed in chronically infected patients but high in patients who have cleared the virus
hepatocyte damage in Hep B
What is the mechanism?
immunologically mediated cytotoxic T cells recognize HBV peptides presented on MHC class I on the cell surface
perinatal transmission of hepatitis B
What percentage of infected infants will be chronic HBV carriers?
What percentage will die of liver cancer?
What is preventive treatment?
from HB-Ag positive mothers to neonate
90% will become chronic HBV carriers
25% will die of liver carcinoma or chronic hepatitis
can reduce incidence of infection with passive immunization with HB-immune globulin and with active immunization after birth
routine screenings of all pregnant women
post-transfusion hepatitis
What is the only problem that persists with obtaining Hep B blood?
no longer a problem because the following not allowed to donate blood:
1: former hepatitis patients
2: people who have lived with a hepatitis patient in the last 6 months
3: people who have had a transfusion in the past 6 months
4: people whose serum test positive for HB-Ag
window period longer when serological test used than with PCR-based test
PCR detection prevents most transmission of HBV and HVC but post transfusion transmission of other hepatitis viruses still a problem
killed vaccines (review)
purified virions are disrupted and the antigens that elicit neutralizing antibodies are purified
chemical inactivation used to eliminate residual live virus
can also clone viral genes that encode neutralizing antibodies and express them in yeast or other microbe
both types of subunit vaccines
subunit vaccines
contain only antigenically important subunits of virions
killed vaccines because no infections virions are present
passive immunization for Hep B
What populations are necessary for pooled IgG?
When is it effective?
pooled human IgG from serum of persons with large amounts of Ab against HBV can protect against overt HBV
used for passive immunization of neonates if needed
pooled normal human gamma globulin usually not adequate (unlike with hep A - for hep B, concentration of antibody in pooled human serum not usually high enough)
also effective post exposure to prevent infection and for infected infants
subunit vaccine for Hep B
Recommended for who?
HB-Ag can be produced in recombinant form
consists of individual viral proteins expressed by yeast or bacteria then purified and formulated with an adjuvant
killed vaccine
recommended for high-risk groups, hospital personnel
because hep B is an STD, infections take place after puberty, so immunization in early childhood is important
hepatitis C virus
What type of Virus is Hep C? Enveloped? Nucleotide status? Diagnostic status? Incubation period? What percentage of infected people have chronic infection?
a flavivirus
enveloped plus-stranded RNA
causes most nonA-nonB hepatits
can be detected by PCR test for the RNA (and by serological, but that’s less sensitive)
transmitted by blood transfusion, needle-sharing, STD
60 day incubation period
results in immunologically mediated damage to hepatocytes
worse than hep B because in hep B on 5% of patients get chronic disease, whereas with hep C 25% get chronic disease
