Hepatitis A Virus

HAV

• Picorna virus  
• Naked Icosahedral capsid with + ssRNA genome
• Fecal oral transmission with high concentrations of infectious virus shed
• Higher incidence in regions with poor sanitation
• Outbreaks in US associated with infected food-handler or contaminated food
• Laboratory Diagnosis using IgM-capture ELISA to detect anti-HAV IgM
• Indicates a current infection
• Anti-HAV IgG indiactes a past infection or immunization--> protection
• Virus Vaccine
• Inactivated virus
• Two IM doses for adults and children > 1 year
• Post exposure immunization within 2 weeks is almost as effective and less expensive than passive immunization with normal human IG 
• If you are infected with HAV and recover you aquire life long immunity
• Incubation perios: 15-45 days, average 21 days
• Diagnosed cases require reporting to CDC

Hepatitis E Virus

HEV

• Hepe virus family
• Nakes icosahedral capsid with + ssRNA genome with four major genotypes
• Highest incidence in areas with poor sanitation
• Endemic countries: genotypes 1,2,4
• US: transmission from infected pigs: genotype 3
• NO VACCINE
• High fatality rate in pregnant women ~20%
• Incubation period: 15-60 days average 40 days

Hepatitis B Virus

HBV

• Hepadna virus family
• Circular partly double stranded DNA genome
• Infectious viron is called a Dane Particle
• lipid enveloped icosahedral nucleocaspid
• HBs Ag envelope  glycoprotein
• HBc Ag capsid protein and DNA genome associated with viral reverse transcriptase
• Infectious virus found in highest concentration in the blood, moderate amounts in semen and vaginal fluid, a small amount in saliva
• Major Route of transmission is blood-borne and sexula but also possible via salia of infected persons producing high levels of Dane particles
• Lab Diagnosis
• HBs Ag Capture ELISA: detection is indicative of current infection
• HBc specific Antibody capture ELISA
• IgM: current acute infection
• IgG and NO IgM  along with HBs indicates chronic infection
• If ONLY anti HBc Ag is present we are in the window period
• Antibody to HBs Ag is NOT detectable in person currently infected with HBV because any anti-HBs IgM or IgM is already bound to huge amounts of HBs Ag present in the serum
• Detection of HBe Ag indicates a high level of infectivity
• PCR or bDNA are used to determine viral load. DOES NOT assay for viral infectivity
• Immunization with recombinant protein subunit vaccine
• Also protective against HDV
• 3 doses with first doest recommended from birth -2 months of age
• If immune anti IgG HBs Ag present
• If immunity from infection then
• Anti IgG HBs Ag
• Anti IgG HBc Ag
• Post exposure prophylaxis of non immue
• Passive HB IG
• First dose of vaccine adminstered
• Must be given in two different sites
• Incubation period 30-180 days, mean 70 days

Hepatitis D Virus

HDV

• No family classification
• Requires HBs Ag in lipid envelope at surface
• - ssRNA  which encodes the Delta antigen
• Can occur as a co-infection or  super infection
• Infection is determined by antibody capture ELISA specific for HDV genome encoded delta antigen
• Active and passive immunization is the same as for HBV alone.
• HBV vaccine is also highly effective vaccine against HDV
• Incubation period of co-infected HBV and HDV is 30-180 days with a mean on 70 days
• Incubation period of HDV superinfection is 15-55 days

Hepatitis C Virus

HCV

• Hepacvirus  genus of the Flavi family
• Lipid enveloped icoshedral capsid with + ssRNA
• 6 major genotypes which differ in response to antiviral therapy
• Viral polyprotein processes by viral protease which can be targeted by specific protease inhibitors
• Injection drug use is major route of transmission, sexual transmission is also important
• Blood transmission is only 10%
• Antibody capture ELISA using recombinant viral protein as reagent to detect total anti-HCV Ig (not IgM specific)
• Recombinant antigen immunoblot assay (RIBA) is used as a confirmatory assay
• RT-PCR or bDNA are also used to screen blood donors and used to determine the viral load or patient with known HCV chronic infection
• NO PASSIVE OR ACTIVE IMMUNIZATION FOR HCV
• Development of highly effective vaccine is unlikely because natural immunization response is relatively poor (85% of infections are chronic)
• Incubation period: 15-50 days, mean 50 days

• Recombinant human interferon-alpha (IFN-alpha) with 48 week duration of 1 injection per week
• Nucleoside reverse transcriptase inhibitors:NRTI
• specific for HBV RNA dependent DNA polymerase
• Ex. lamivudine= 3TC

Chronic Hepatitis C anti-viral therapy

• Recombinant human INF-alpha for 48 weeks duration, 1 injection/week
• Weekly INF alpha injection combined with daily dose of ribavirin in a therapy known as Rebetron with 48 weeks duration
• 2010 reports of vitamin D supplementation increasing sustained virological respsonse to rebetron but not yet known in Rebetron + HCV PI
• 2 specific protease inhibitors (HCV PI) licensed in May 2011 for use in combination with Rebetron.
• Specifically increases therapy for infections with predominant genotype 1 virus 

1. Symptoms delayed after peak of viral replication, co-incidental with mainfestation of aquired immune response
2. Preicteric Phase- duration of 3-10 days: malaise and weakness, followed by anorexia, nausea and vomiting.  Dull pain in the upper right quadrant.
3. Icteric Phase- Duration of 1-3 weeks; jaundice and or dark urine, dramatic increase in serum aminotransferase. Release of these enzymes from hepatic cells is indicative of liver damage from virus, chemical or other toxic agents.
4. Convalescent Phase- malaise and weakness may persist for weeks with relapse or prolonged illness up to 6 months duration with Hepatitis A  

1. Infectious virus shed in feces for one or several weeks prior to symptoms (dark urine, bilirubin) and shedding ends before termination of symptoms
2. Anti-viral IgM detectable during clinical phase and disappears after several months
3. Anti-viral IgG persists for long periods and is indicative of protection from re-infection
4. No chronic infections with HAV or HEV but infection may persist for many months in those with severe immunodegiciencies  

• Chronic infection (characterized by HBs Ag + for > 6 months)
• in almost all infants infected at birth.
•  50% rate for infection at 12 months
• 10% rate of infection of older children and adults
• Reason why HBV vaccine is recommended at earliest time of any human vaccine.  Birth -2 months
• Chronic infection may be subclinical, or chronic active.  Can potentially lead to cirrhosis and or primary hepatocellular carcinoma
• Acute HBV infection may be subclinical, icteric, or fulminant in rare cases.
• Liver transplant may by indicated in rare cases of fulminant HBV and cases of chronic HBV.  Immunoprophylaxis with HBIG to prevent recurrence

• High rate of chronic infections in adolescents and adults-85%
• "End stage liver disease" (cirrhosis) due to chronic HCV is currently one of the major reasons for liver transplanation in the US but recurrence of HCV infection is a common problem which is not easly treated with combination therapy.