Diebel: Viral Hepatitis Flashcards
What are the major causes of viral hepatitis?
Hepatitis A Virus (HAV) Hepatitis B Virus (HBV) Hepatitis C Virus (HCV) Hepatitis D Virus (HDV) Hepatitis E Virus (HEV)
Hepatitis G Virus (HGV)
Yellow Fever Virus (YFV)
What forms of hepatitis cause ONLY acute infections?
HAV
HEV
What forms of hepatitis cause acute and chronic infections?
HBV
HCV
HDV
HGV
RNA virus Icosahedral Nucleocapsid Enveloped SS (+) Nonsegmented Genome (Class IV) Flaviviridae Pegvirus
Hepatitis G virus (GBV-C) in the same family of viruses as…
HCV
YFV
What is the infection pattern for GBV-C? Distribution?
Hepatotropic
Global
How big is the genome of Hepatitis G?
~9,400 nucleotides and encodes for a single large polyprotein.
How is GBV-C transmitted?
Exposure to contaminated blood products is the route of transmission in humans.
multiple blood transfusions, IV drug users at risk
Individuals w/ GBV-C are likely to be co-infected w/ …
HBV
HCV
or both viruses.
What is the significance of Hep G?
May infect lymphocytes and may be an important co-infection that can dictate the course of HIV infections
How do you dx HGV?
Identified in infected individuals by the detection of the genome by RNA detection methods like RT-PCR
HAV
picornaviridae
no envelope
(+) ssRNA, Group IV
HBV
hepadnaviridae
enveloped
Partially dsDNA, Group VII
HCV
flaviviridae
enveloped
(+) ssRNA, Group IV
HDV
Deltavirus
enveloped
(-) ssRNA, Group V
HEV
Calciviridae
nonenveloped
(+) ssRNA, Group IV
What hepatitis viruses have fecal oral transmission?
HAV
HEV
What hepatitis viruses can be transmitted through blood or sexual contact?
HBV
HCV
HDV
What hepatitis viruses ahve a short incubation period (2-8 wks)?
HSV
HEV
What viruses have a long incubation period (2-24 wks)?
HBV
HCV
HDV
What viruses can cause acute infection?
all of them
What viruses cause a chronic infection?
HBV
HCV
HDV
HEV
HAV
Dx?
Therapy?
Vaccine?
Anti-HAV IgM, IgG (prior infection)
Supportive care, pooled immune globulins
yes
HBV
Dx?
Therapy?
Vaccine?
Multiple serological markers
a-interferon, lamivudine, hepatitis B immune globulin
Yes
HCV
Dx?
Therapy?
Vaccine?
Anti-HCV antibody, RT-PCR
a-interferon, ribavirin, boceprevir, telaprevir
No (viral antigens vary over the course of an infection)
HDV
Dx?
Therapy?
Vaccine?
Anti-HDV delta-antigen IgM
Same as HBV
No (vaccination against HBV is effective)
HEV
Dx?
Therapy?
Vaccine?
Anti-HEV IgM, IgG, ruling out HAV infection
None
No
What viruses only cause acute hepatitis?
HAV
HEV
Describe the structure of the HAV.
small, naked virus with a (+) ssRNA genome ~7,500 nucleotides long.
What is the VPg protein?
VPg protein is covalently attached to the 5’ end and the genome contains a polyA tail
What is unique about the capsid structure of HAV?
one of the most stable of all picornaviruses and is stable at pH 1, resistant to destruction by many solvents and detergents and desiccation.
How can HAV be inactivated?
chlorine treatment of drinking water
formalin treatment
UV radiation
How is HAV transmitted?
fecal oral
How does HAV infect cells?
Infects cells expressing the HAV cell receptor 1 glycoprotein (HAVCR-1).
(Found on liver cells and T cells)>
Virus replicates in large quantities in the liver and is shed in the stool approximately 10 days before the onset of jaundice.
What leads to the pathogenesis and disease associated w/ an HAV infection?
immune response to virally infected liver cells
What percent of acute hepatits cases are caused by HAV?
40%
How does HAV spread in the populatio?
spreads rapidly b/c most ppl are contagious 10-14 d prior to onset of sxs
90% of all children and 25 to 50% of infected adults have asymptomatic, productive infections.
A pt presents w/ fever, fatigue, nausea, loss of appetite, abdominal pain, dark urine and jaundice.
Dx?
HAV
Symptoms occur 15 to 50 days post-exposure and intensify for 4 to 6 days.
Complete recovery 99% of the time
How do you dx an acute HAV?
Acute infection shown by ELISA of anti-HAV IgM
What is given to contacts of a HAV infected individual?
Prophylaxis with immune globulin serum.
Who is the killed HAV vaccine given to?
Given to children and adults at high risk for infection.
Travelers to endemic regions.
Administered to children 2 years of age and to adults in conjunction with the HBV vaccine.
How does HEV compare to HAV?
Sxs and transmission are almost identical to HAV.
Symptoms of disease occur slightly later than seen with HAV and the disease is slightly more severe with an overall mortality rate of around 1 to 2%.
Who is HEV particularly dangerous for?
Disease is particularly dangerous for pregnant women with a mortality rate of ~20%
What may be responsible for the more severe disease outcome of HEV?
immunological and hormonal factors
the maternal immune system is altered. T cells are reduced up to the 20th week of gestation. This has been speculated to lead to an increased susceptibility to viral infections such as hepatitis, rubella, herpes, and HPV.
Levels of HCG are up and have a suppressive effect on cell-mediated immunity.
Liver damage is still through immunological mediated injury… ?
How do you dx HEV?
Tx?
Presence of anti-HEV antibody or HEV RNA.
No treatment available
How are HAV and HEV transmitted?
Transmitted via the fecal to oral route.
Ingestion of contaminated food and water can cause infection.
HAV in shellfish from sewage-contaminated water.
Viruses can be transmitted by food handlers, day-care workers, and children
What are RF for HAV and HEV?
overcrowded unsanitary cities
Who is at risk for HAV/HEV?
Children – mild disease, major source of the spread of HAV
Adults – abrupt-onset hepatitis
Pregnant women – high mortality rate with HEV infections
how is the spread of HAV and HEV controlled?
good hygiene
HAV passive antibody protection for contacts
HAV vaccine
What hepatitis viruses cause acute and chronic hepatitis infections?
HBV, HDV, and HCV
What is the infectious virion of HBV?
Dane particle
What is the route of infection for HBV?
Bloodborne pathogen
Infects liver cells expressing the transferrin receptor, asialoglycoprotein receptor, and the human liver annexin V protein using the HBV HBsAg viral protein.
Virus causes acute or chronic, symptomatic or asymptomatic diseases. The individual’s immune response to the initial infection dictates the outcome of the disease.
How does HBV spread w/in the body?
The major source is in the blood but it can also be found in semen, saliva, milk, vaginal and menstrual secretions, and amniotic fluid
WHen are sxs associated w/ HBV observed?
The virus starts to replicate in the liver within 3 days of exposure. Symptoms of infection may take up to 45 days
What characterizes the clinical syndrome of HBV?
long incubation period
insidious onset
How do you prophylactically tx HBV? Who is it given to?
Prophylaxis with immune globulin serum.
- -Given to newborns of HBsAg mothers to ameliorate disease.
- -Given to individuals within a week of exposure to prevent disease
How do you tx a chronic HBV infection?
Lamivudine (HIV RT inhibitor)–targets the viral pol, taken for 1 year
Adefovir, dipivoxil, and famciclovir – nucleoside analogues. Taken for 1 year.
Pegylated interferon-a can also be taken. Taken for at least 4 months
HBV vaccination is recommended for what groups?
infants
children
people in high risk groups
What groups are at high risk for HBV?
People from endemic regions Babies of mothers with chronic HBV IV drug users People with multiple sex partners People needing multiple blood transfusions Health care personnel
What is the route of infection fo HDV?
Bloodborne
HDV can only affect what cells….
cell that are already infected w/ HBV (requires HBsAg for packaging)>
rapid, severe progression of infection in individuals who are already HBV carriers
What virus is responsible for causing 40% of fluminant hepatitis infections?
HDV
How do you dx HDV?
detecting the RNA genome (RT-PCR), the delta antigen, or anti-HDV antibodies (ELISA)
How do you tx HDV?
No specific treatment for HDV.
Treating and preventing HBV infections also works to clear and prevent HDV infections
What percent of all HCV infections become chronic infections? What do chronic infections lead to?
70-80% of all infections become chronic infections
Chronic infections lead to degenerative liver disease
Cirrhosis or hepatocellular carcinoma, liver failure
How is HCV transmitted?
blood-borne pathogen transmitted through recreational drug use, needle sharing, blood transfusions prior to 1992
How long does it take before HCV sxs appear?
10-20 yrs post infection
How does HCV infect liver cells?
Infects liver cells expressing CD81 surface receptor (also seen on B lymphocytes)>
Uses the lipoprotein receptor to facilitate uptake into hepatocytes>
HCV proteins inhibit cellular apoptosis and interferon-a>
promotes persistent infection.
Where is HCV most prevalent?
southern Italy, Spain, central Europe, Japan, and parts of the Middle East
How do you dx HCV?
ELISA recognition of the anti-HCV antibody or detection of the RNA genome.
Genome detection, quantitation, and genotyping by RT-PCR are the gold standard for confirming the diagnosis of HCV and for planning the correct course of treatment against the infection.
How do you tx HCV?
Recombinant interferon-a or pegylated interferon-a
ribavirin
boceprevir
telaprevir.
How is yellow fever spread?
Aedes mosquito
How does YFV cause infection?
cytolytic virus that destroys cells it infects>
systemic disease>
IR to infection is both humoral and cellular and can destroy tissues
A pt presents w/ a severe systemic disease, flu-like syndrome, hemorrhagic fever, shock and loss of liver/kidney/heart function.
Dx?
YFV
How do you dx YFV?
IF, RT-PCR, ELISA
Direct isolation of virus
How do you tx YFV?
Supportive care
vector control measures
vaccination (Yellow Fever Virus live-attenuated vaccine).
