What family and genus does HAV belong to?
Picornaviridae and Enterovirus
What is the structure of HAV?
Nonenveloped icosahedral capsid ss RNA (+) (less than 7 kb)
What family and genus does HEV?
Family Caliciviridae and Hepevirus
What is the structure of HEV?
Nonenveloped icosahedral capsid 7.5 kb ss RNA (+)
What are the reservoirs of HAV? HEV?
HEV: Possible swine, mostly prevalent in developing countries, only causes FLF in pregnant women
Describe the pathogenesis of HAV
It is contracted via a fecal-oral route, with replication occuring in the GI tract during the ~2 week incubation period. Contraction is most common early disease
How does HAV present?
Often asymptomatic with symptoms including anorexia, malaise, fever, HA, and possibly jaundice over a 4-5 week period
What groups are at risk fo HAV?
-Household or sexual contacts
-Travelers to endemic areas
-Inhabitants of American Indian reservations
-During outbreaks: Diners, Day care center workers, Gay men, Injecting drug users
How is HAV diagnosed?
-Presumptive diagnosis on appearance and history
-Detection of anti-HAV IgM
What vaccine options are available for HAV?
-Passive immunization with gamma globulin
-Inactivated vaccine (Havrix) in those 2 years of age or older
-Combination vaccine for HAV and HBV (Twinrix): Havrix plus recombinant HBV vaccine. Only for those 18 years of age or older
-Vaccine or gamma globulin is recommended for travelers to endemic areas
Hepatitis Virus Nomenclature
HCV: “nonA, nonB” PT-hepatitis
HDV: dependent on HBV for infection
HEV: “nonA, nonB” ET-hepatitis
Describe the structure of HBV?
Enveloped virus termed Dane particle
Partially ds DNA genome, 3200 bp
Structure: Circular coat protein (HBsAg) surrounded circular core (HBcAg) containing DNA genome and polymerase
What are the 5 major proteins of HBV?
DNA polymerase (reverse transcriptase)
HBsAg: surface antigen, attachment protein (Mostly found in 20 nm particles and filaments)
-HBcAg: core antigen, capsid protein
-HBeAg: derivative of HBcAg, important serolgic marker
-X antigen: influences gene expression
How does HBV replicate?
Fusion endocytosis followed by uncoating of the core, completion of ds DNA genome and then entry into the nucleus for transcription. Translation occurs in the cytosol via reverse transcriptase to produce a partial ds DNA genome, which is then mostly maintained extrachromosomally in chronic infections
Where is HBV most common?
-Endemic to China and sub-Saharan Africa
-Late infection in US and Europe
How is HBV transmitted?
Virus is present in blood, semen, and vaginal secretions
Transmission is by parenteral route
-Injection drug use
-Perinatal at delivery
What does a positive HBsAg suggest?
carrier or acute infection of HBV
What does a positive Anti-Hb Ab suggest?
a pt has had HBV or received vaccine
What does a positive HBeAg suggest?
these pts are at an increased risk of transmission (positive Anti-HBe is used to ID HBsAg carrier with low risk of transmission)
What does a positive Anti-HBc suggest?
ID of persons with past infection
What does a positive IgM Anti-HBc suggest?
ID of acute or recent infection
-Encodes delta antigen, its core protein
-Enveloped, circular ss RNA genome of 1.7 kb
-HDV particles must incorporate HBsAg to infect hepatocytes
What is the family of Hep C?
Describe the structure of Hep C
-Enveloped icosahedral capsid
-9.4 kb ss RNA (+) genome
What are the genotypes of HCV?
-6 major genotypes, further divided into subtypes
-1a, 1b, 2a, 2b are worldwide
-1a and 1b are most common in US
-Patients also contain quasi-species
Where is HCV most common?
Highest incidence in Asia, Middle East and Nort Africa with incidence dropping in the US
What are the risk factors of contracting HCV?
Born between 1945-1965 (80% of chronic cases)
Illicit (injection) drug use
Perinatal infection at birth
T or F. Acute infections of HCV are milder than HBV
How does the immune system affect hepatitis?
Hepatitis viruses are not cytolytic
Immune destruction (cytotoxic T cells) of infected hepatocytes leads to liver disease
What most commonly causes chronic hepatitis?
-40% of cases are due to HCV
-20% due to HBV
-5% contain HDV
-Remainder of unknown origin
The development of chronic HBV depends heabvily on what?
the age of initial infection
< 1 yo: 90% chronicity rate
1-5 yo: 30% rate
> 5 yo: 2% rate
How deadly is chronic HBV?
25% mortality, most commonly in the 60s
What are the stages of chronic HBV?
-Immune tolerance phase
-Immune clearance phase
What are the major outcomes of acute Hep B?
90% resolve, 1% lead to fulminant hepatitis, and 9% progressive to chronicity (HBsAg+ for 6+ mos)
What are the major outcomes of chronic Hep B?
-asymptomatic carrier state
-chronic persistant hepaitis or chronic acute hepatitis leading to cirrhosis, HCC, and/or extrahepatic disease
What are the major outcomes of untreated acute HCV?
85% on untreated will lead to chronic infection leading to liver failure, cirrhosis, or HCC
Immunize HBV and HCV chronic patients against HAV
Discourage alcohol use
HBV and HCV liver disease is the leading reason for liver transplants
Despite HBV vaccine, HBV-related cancers and deaths have doubled in the past decade
Diagnosis of Hep at presentation
1) Acute forms of ET- and PT-hepatitis can be similar
2) Determine Source of infection and ELISA
-HBV: HBsAg, anti-HBc IgM; HBeAg, HBe antibody, HBV DNA
-HCV: anti-HCV antibodies, HCV RNA
3) Determine HCV genotype
Screen blood supplies for HBsAg, HBc antibodies, HBV DNA
-Yeast expressed HBsAg
-Childhood immunization recommended
HBIg for exposed individuals
-Can be used prophylactically for travelers
What is the goal of HBV antivirals?
Goal is to reduce the risk of progressive chronic disease, transmission, and complications (cirrhosis, HCC)
What are some indications to initiate HBV antiviral therapy?
>2000 units/mL HBV DNA
>2x upper normal limit of serum ALT
Screen blood supplies for antibodies to core antigen, HCV RNA
-No vaccine in US yet, no passive immunization
-“HCV is relatively easily treated and can be eliminated in almost all patients.”
-Thus, goal of therapy is to eliminate HCV RNA
-Treatment varies by genotype