• 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

• hepevirus (+ssRNA) w/no envelope
• transmission: fecal/oral, parenteral?
• incubation period: 40 days (15-64)
• sperical with icosahedral symmetry

• 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)

• delta virus
  • ssRNA circular
  • envelope
• transmission- parenteral
• incubation period: 40-180 days

• flavivirus
  • +ssRNA
  • w/ envelope
• transmission- parenteral, sexual
• incubation peroid: 50 days (14-180)
• morphology- spherical

• HepA: whole virus vaccine
• HepB: HB Ag vaccine
• HepC: in development
• HepD: immunization for HBV
• HepE: capside (ORF2) vaccine in development

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

• 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

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

• 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

• 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)

• 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

• 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

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

• 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

• 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

• 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%

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)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• clearance of HBV DNA
• loss of HBeAg
• seroconversion to HBeAb
• normalization of ALT
• histologic improvement

• 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

• 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

• infection only in those who are HBsAg positive
• commonly in those with multiple parenteral exposures
• three different genotypes

• acute infection simultaneously with HBV and HDV
• prognosis: acute and self limiting
  • chronic HDV rare

• 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

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

• 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)

• 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

• 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

• relapsing and remitting symptoms
• ALT may be near normal despite biopsy proving advanced disease

• late complication- hepatocellular carcinoma
  • usually in patients with cirrhosis
• extrahepatic manifestations associated with chronic infection
  • cryoglobinemia

• 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

• 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