Shared Flashcard Set

Details

Microbiology- Virology
Hepatitis Viruses (T Pierce)
40
Medical
Professional
11/13/2009

Additional Medical Flashcards

 


 

Cards

Term
hepatitis A: transmission, general incubation period, genetic structure, morphology, stability
Definition
  • picornavirus
    • +ssRNA
    • no envelope
  • transmission- fecal, oral
  • incubation- 28 days (15-50)
  • morphology- spherical with icosahedral symmetry
  • stability
    • resistant to heat, solvents, acids
    • destroyed by 5 minutes of boiling
Term
hepatitis E: genetic characteristics, transmission, incubation period, morphology
Definition
  • hepevirus (+ssRNA) w/no envelope
  • transmission: fecal/oral, parenteral?
  • incubation period: 40 days (15-64)
  • sperical with icosahedral symmetry
Term
hepatitis B: genetic characteristics, transmission, incubation period, Ag structure
Definition
  • hepadna virus
    • circular, partially dsDNA
    • w/ lipid envelope surrounding inner core
  • transmission
    • fecal-oral
    • parenteral
    • sexual
  • incubation: 120 days (40-160)
  • HBsAg on surface
  • inner core
    • HBcAg (core Ag)
    • HBeAg (marker of infectivity)
Term
hepatitis D: genetic characteristics, transmission, incubation period
Definition
  • delta virus
    • ssRNA circular
    • envelope
  • transmission- parenteral
  • incubation period: 40-180 days
Term
hepatitis C: genetic characteristics, transmission, incubation peroid, spherical
Definition
  • flavivirus
    • +ssRNA
    • w/ envelope
  • transmission- parenteral, sexual
  • incubation peroid: 50 days (14-180)
  • morphology- spherical
Term
hepatitis immunizations
Definition
  • HepA: whole virus vaccine
  • HepB: HB Ag vaccine
  • HepC: in development
  • HepD: immunization for HBV
  • HepE: capside (ORF2) vaccine in development
Term
HepA: viral replication
Definition
  1. virus enters hepatocyte via unknown cellular receptor
  2. uncoating of viral partical, release of +sense RNA genome
  3. translation of viral polyprotein
  4. polyprotein undergoes proteolytic processing by viral and cellular proteases
  5. RNA dependent RNA polymerase synthesis of - strand copy of viral genome
  6. - strand RNA is used as a template for synthesis of + strand RNA
  7. + strand RNA is packaged into new viral particles
  8. HAV particles secreted by cell across the apical membrane of the hepatocyte into the biliary canaliculus
  9. from which they are passed into the bile and small intestines
Term
HepA epidemiology
Definition
  • worldwide distribution with highest prevalence in Africa and Asia
    • related to crowding and poor hygiene
  • virtually all adults in developing countries are seropositive
  • in US, most of those with Ab found in west and southwest and among Native Americans
  • transmission: fecal-oral route, especially in children
    • person to person in housholds
      • daycare centers, infected food handler
    • food and waterborne via raw or partially undercooked shellfish
Term
HepA pathogenesis
Definition
  1. virus pass thru stomach and is transported to liver, where it replicates in hepatocytes
  2. shed from infected hepatocytes into bile canaliculi and sinusoids
    • hepatocyte damge mediated by cell mediated immune response
      • liver disease coincident with immune response
      • mainly CD8 cells (MHC restricted) 
  3. passes into intestines and is excreted
Term
HepA clinical manifestations
Definition
  • often subclinical
    • proportion of symptomatic infections increases with age
  • begins as flu like symptoms
  • first specific sign: DARK URINE
  • followed by bilirubinemia
    • pale feces
    • icteric sclera
    • jaundice
  • physical exam: hepatomegaly, jaundice
  • lab findings: elevated transaminases
  • resolve symptoms by end of 3rd week
  • NO CHRONIC HEPATITIS
  • RARE fulminant hepatitis
Term
Hep A dx, tx
Definition
  • dx
    • HAV IgM to whole virus
    • IgG persists for years and confers immunity (so if you see IgG in person who is sick, Hep A aint the reason)
  • tx- supportive (most of time, disease self limited)
Term
HepA prevention
Definition
  • improve sanitation
  • avoid raw shellfish
  • passive immunization- post exposure pooled ISG for clos contacts (mainly for travelers)
    • 85% protection rate
  • active immunization- formalin inactivated viral particles
    • protection rate near 100%
    • recommended if increase risk of acquiring, transmitting HAV, or of developing fulminant hepatitis due to pre-existing liver condition

 

Term
HEV epidemiology
Definition
  • worldwide prevalance
  • highest attack rate age range: ages 15-40
  • transmission: fecal oral
  • many waterborne outbreaks (mainly in developing countries)
  • spread by blood or blood products (ex: US blood donors)
  • reservoirs (seroprevalance of farmers with swine contact in Iowa)
    • domestic swine
    • wild deer
    • boars
Term
HEV pathogenesis
Definition
  1. pseudoglandular rearrangement of hepatocytes and intrahepatic cholestatsis
  2. disease is immune mediated (like HepA)
  3. no progression to chronic hepatitis and no persistent infection (like HepA)

We do not know weither or not it replicates in the GI tract like HepA

Term
HEV clinical manifestations
Definition
  • natural history similar to Hep A
  • infection usually subclinical, especially in children and young adults
  • pregnancy- fulminant hepatitis if acquired in 3rd trimester
    • high mortality
    • could be due to hormones, geographic differences, or switch to Th2 immunity

 

Term
HEV: dx and tx
Definition
  • dx
    • IgM anti-Hep E Ab
      • Ab to capsid/ORF2
      • HEV RNA via PCR
  • tx- supportive (disease is self limiting in vast majority of cases
Term
HEV prevention
Definition
  • passive immunization- no evidence for protective Ab in commercial ISG
  • active immunization
    • recombinant capsid protein (ORF2)
    • administered in 3 doses at 0, 1, and 6 months
    • efficacy of 95%
Term
HepB replication
Definition
  1. fuse with host cell membrane
  2. viral capside released into cytoplasm
  3. ds genome completed by enzymes contained within core
  4. capside enters nucleus where there is transcription to genomic and mRNA
  5. RNA enters cytoplasm where there is translation of viral proteins
  6. core assembles around + sense RNA
  7. + sense RNA is copied to - sense DNA, THEN to + sense DNA
  8. core passes through cytoplasmic membranes (ER, golgi) and becomes enveloped with HBsAg on its surface
  9. fusion of outer membrane with cell membrane leads to viral release (end with virus with partially dsDNA)
Term
HepB epidemiology
Definition
  • most primary infections in young adult males
  • important predictors of persistent infection
    • age at primary infection
      • the younger you are when you get a primary infection, the higher risk you have of going to chronic HBV
    • severity of initial disease
  • Asia, Africa- vertical transmission and chronic hepatitis more common
Term
HepB transmission
Definition
  • blood and body fluids
    • sexual contact
    • needle sharing
    • transfusion
      • blood bank testing for ALT, HBsAg, HBV DNA
      • do a minipool of a certain amount of specimens for HBV DNA
        • it positive, do each in that minipool individually
  • vertical transmission
    • esp. if mother HBsAg positive and HBeAg positive
  • percutaneous exposure
    • esp. w/needlestick where patient HBsAg positive and HBeAg positive
Term
HepB pathogenesis
Definition
  • acute and chronic hepatitis B are syndrome of hepatocellular necrosis and inflammatory response
  • cytotoxic T cell response directed at HBsAg/ HBeAg on HBV infected hepatocytes
  • much of liver damage caused by host inflammatory response
Term
HepB: clinical manifestations of acute infection
Definition
  • infection may be subclinical, mild/anicteric, or severe
  • prodromal symptoms- flu like
  • anorexia, nausea/vomitting, abdominal pain, may be followed by jaundice
  • physical exam: enlarged, tender liver
  • lab finding- elevated transaminases and bilirubin
  • rare to have fulminant hepatitis with encephalopathy, seizures, and ascities
  • extrahepatic manifestations- related to circulating HBsAg-HBsAb complexes
    • polyarteritis nodosa
    • glomerulonephritis
Term
HBV: clinical manifestations with chronic hepatitis
Definition
  • chronic persistent hepatitis
    • persistent or recurrent elevations of transaminases, mild hepatomegaly, no evidence of progression
  • chronic active hepatitis
    • intermittent jaundice with significant elevation of transaminases
    • many will progress to cirrhosis and hepatic failure

Strong association btw persistant infection and hepatocellular carcinoma

Term
Hep B: dx of self limited primary infection
Definition
  • HBsAg = active infection
    • first marker to appear
    • titers fall several weeks after resolution of hepatitis
  • HBeAg = infectivity
    • level rises and falls in parallel with HBsAg
    • marker of active viral replication
  • HBV DNA (parallels other markers of disease activity)
  • HBcAb
    • IgM and IgG appear 3-5 wks after appeaarance of HBsAg
    • IgG Ab persists
  • HBsAb
    • appear several months after disappearance of HBsAg
    • protects from reinfection
  • HBeAb
    • signals less viral replication, leading to better clinical outcome
Term
HepB dx of chronic infection
Definition
  • HBsAg
    • if positive after 20 wks, its likely positive indefinitely
  • HBeAg
    • some w/persistent HBeAg, highly contagious
    • highest risk for hepatocellular carcinoma
  • HBcAg persists
  • HBsAb- no seroconversion to HBsAb (if you been immunized, you have this Ab)
  • HBV DNA- level depedent on disease activity, can be measured quantitatiely
Term
Hep B tx
Definition
  • acute hepatitis- supportive
  • chronic hepatitis
    • response reduce risk of cirrhosis and hepatocellular carcinoma
    • nucleoside analogues (PO)
      • directly inhibit HBV replication
    • alpha interferon/pegylated interferon alpha 2a
      • IV side effects
Term
Hep B: goals of therapy
Definition
  • clearance of HBV DNA
  • loss of HBeAg
  • seroconversion to HBeAb
  • normalization of ALT
  • histologic improvement
Term
Hep B virus: prevention
Definition
  • pre-exposure immunization
    • vaccine made of HBsAg particles expressed in yeast
  • post exposure immunization
    • hep B Ig (HBIG) for babies
      • prevention of mother to child transmission
Term
Relationship between Hepatitis B and D
Definition
  • Hep D envelop contains HBsAg
  • assembly of intact HDV virons and pathogenicity requires the helper function of HBV

There is no Hep D without Hep B

Term
HDV epidemiology
Definition
  • infection only in those who are HBsAg positive
  • commonly in those with multiple parenteral exposures
  • three different genotypes
Term
HDV: coinfection (definition, prognosis)
Definition
  • acute infection simultaneously with HBV and HDV
  • prognosis: acute and self limiting
    • chronic HDV rare
Term
HDV: superinfection (definition, prognosis)
Definition
  • acute HDV is superimposed on chronic HBV infection
  • prognosis
    • acute Hep D is severe and protracted
    • associated with significant morbidity and mortality
    • chronic HDV develops most of the time
Term
Hep C: replication
Definition
  1. lipid envelop fuse with cell membrane releasing nucleocapsid intracellularly
  2. after uncoating, translation and polyprotein processing
    • assemble structural and non structural proteins at ER
  3. RNA replication
    • HCV RNA replication occurs in a specific membrane alteration, the membranous web
  4. subsequent packaging and assembly
  5. virion maturation and release
Term
Hep C: epidemiology
Definition
  • highest prevalence in middle east
  • transmission
    • blood and body fluids
      • most needle sharing (MOST COMMON)
      • blood transfusion (RARE)
      • sexual contact (has risen some recently)
      • needlestick exposure (RARE)
Term
Hep C pathogenesis
Definition
  • infection become persistent in most cases
  • although there is Ab response to HCV, complete neutralizing immune response not induced
  • liver disease usually progresses slowly
  • liver damage immunologically mediated (like Hep B)
  • important cofactor in development of chronic liver disease- alcohol abuse
Term
Hep C clinical manifestations of acute infection
Definition
  • clinically indistinguishable form other causes of hepatitis
  • most cases are anicteric
  • symptoms are usually milder and elevations of ALT less pronounced than w/ Hep A and Hep B
Term
Hep C clinical manifestations in chronic infection
Definition
  • relapsing and remitting symptoms
  • ALT may be near normal despite biopsy proving advanced disease
Term
Hep C complications
Definition
  • late complication- hepatocellular carcinoma
    • usually in patients with cirrhosis
  • extrahepatic manifestations associated with chronic infection
    • cryoglobinemia
Term
Hep C dx
Definition
  • HCV IgM/IgG Ab (to core, NS3, NS4)
    • but this will not distinguish between acute and chronic infection
  • recombinant immunoblot assay (RIBA) is confirmatory
  • HCV RNA
Term
Hep C tx
Definition
  • pegylated alpha interferon with ribavirin
    • decreases ALT levels
    • reduces viremia
    • improves histopathology
    • indications
      • pts with persistently elevated ALT levels
      • detectable HCV Ab
      • HCV RNA
      • evidence of fibrosis on biopsy (active inflammation)
    • poor response with some genotypes
    • there is a greater than 50% relapse rate
Supporting users have an ad free experience!