Lecture 11: Virology -Hepatitis Viridae Flashcards
1) Viral hepatitis and liver enzyme elevation 2) Epidemiology, serology, and treatment of Hepatitis A virus 3) Transmission, pathogenesis, serology, and treatment of Hepatitis B virus 4) Transmission, manifestations, diagnosis, and treatment of Hepatitis C virus 5) Hepatitis D, E, and G viruses
Viral Hepatitis
Infection of liver hepatocytes by viruses
5 RNA Hepatitis Viruses
Hep A (HAV) Hep C (HCV) Hep D (HDV) Hep E (HEV) Hep G (HGV)
1 DNA Hepatitis Virus
Hep B (HBV)
Acute Viral Hepatitis
- what?
- ________ incubation period
- symptoms
- enzymes produced
sudden illness with a mild to severe course followed by complete resolution
- variable incubation period
- flu like symptoms
- 1-2 wks later patient develops jaundice
- necrosis of hepatocytes produces enzymes aspartate aminotransferase (AST), alanine aminotransferase, gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase
Chronic Viral Hepatitis
- what?
- which strains?
- why is diagnosis difficult?
prolonged course of active disease or silent asymptomatic infection
- HBV, HCV, & HDV can cause chronic hep
- diagnosis difficult due to patient being asymptomatic with only an enlarged tender liver and mildly elevated liver function enzyme levels
Hepatocytes produce ____ and ____. The cells that line the bile canaliculi produce _______________ and ______.
AST; ALT
alkaline phosphatase; GGT
Cell necrosis results in release of ___ and ____
AST; ALT
Initially there is high ___ and ____ & little elevation in _____________ and _____
AST; ALT
alkaline phosphatase; GGT
As infection worsens, the liver ____ and the canaliculi _________, resulting in a backup of ____________ in the blood
swells; narrows; bilirubin
Hepatitis A Virus
- structure
- family?
- transmission
-naked icosahedral capsid with (+) ssRNA nucleic acid
family picornaviridae
-transmitted by fecal-oral route
Hepatits A Virus
-Epidemiology
- 6000 cases reported each year in the US
- Poor hand washing, persons ingesting fecally contaminated drinking water, close person-to-person contact in institutions such as day care
Hepatitis A Virus
- Serology
- > what part is antigenic?
- > which immuniglobulins?
- > active vs old infection
- HAV capsid is antigenic; host production of anti HAV IgM and later anti-HAV IgG
- Patient with active infection has anti-HAV IgM detectable in the serum
- Anti-HAV IgG indicates old infection, no active disease
Hepatitis A Virus
-Treatment
- inactivated Hepatitis A vaccine recommended for high risk adults
- once exposed, pooled immune serum globulin will prevent or decrease the severity of infection, if given early
Hepatits B Virus
- Structure
- > family
- > size
- > genome
- intact virus is called what? and is composed of?
- Hepadnavirus
- HBV= BIG and BAD
- Big virus (42 nm) with an enveloped icosahedral capsid and circular dsDNA
- intact virus is callled Dane particle composed of an envelope and capsid studded with protein spikes
Hepatitis B Virus
-Viral Proteins
4 viral proteins encoded by viral DNA:
1) Capsid protein (hep B capsid antigen) [HBcAg]
2) Envelope protein (hep B surface antigen) [HBsAg] -anti-HBsAg are protective
3) Multifunctional reverse transcriptase/DNA polymerase
4) Nonstructural regulatory protein, X protein
Hepatitis B Virus
- Transmission
- > found where?
- > titer amount as high as?
- > soluble component of the core is? serves as what?
- > pregnant mothers
- found in all human body fluids of an infected patient and serves as a source of infection
- titer of virus in acute infection is as high as 10^8 virus particles /ml
- during active infection, a soluble component of the core is released called HBeAg, a marker for active disease and a highly infectious state
- pregnant mothers with HBeAg in their blood have a 90% transmission rate to offspring
Hepatitis B Virus
-Pathogenesis
Causes both acute and chronic hepatitis. Disease states caused by HBV:
- Acute hepatitis
- Fulminant hepatitis -severe acute hepatitis with rapid destruction of the liver
- Chronic hepatitis: (see next notecard)
Hepatits B Virus
Pathogenesis
->Chronic Hepatits
- Asymptomatic carrier -never develops antibodies against HBsAg (anti-HBsAg)
- > Chronic-persistent hepatitis: low grade “smoldering” hepatits
- > chronic active hepatitis: acute hepatits continuing without normal recovery (lasts longer than 6-12 months
- > co-infection with hepatitis delta virus (HDV)
- liver injury is due to cell-mediated immune response
- HLA-I-restricted cytotoxic T cells, react specifically with HBcAg and HBeAg expressed on surface of infected hepatocytes
- immune complexes of antibody and HBsAg can deposit in tissues and activate immune system resulting in arthritis, skin, and kidney damage
What is an indication that an HBV infection has become chronic?
the continued presence of HBsAg beyond 6 months and the absence of anti-HBs
Hepatitis B Virus
-Serology
(see slide 18)
HBsAg -indicates live virus and infection
->HBsAg = Disease
->Anti-HBsAg = Immune, Cure, No active disease
HBcAg -antibodies to HBcAg are not protective
->IgM anti-HBcAg = New infection
->IgG anti-HBcAg = Old infection
HBeAg -indicates high infectivity and active disease
->HBeAg = High infectivity
->anti-HBeAg = Low infectivity
The currently used vaccine, containing recombinant hepatitis surface antigen, elicits only ___________ antibody, which is the __________ antibody.
anti-HBsAg; neutralizing
Hepatitis B Virus
-Treatment
- Active Immunization
- Anti-viral agents:
- > Interferons (IFN-alpha) suppress HBV DNA levels and leads to seroconversion of HBeAg in around 35% of chronic HBV patients
- > Nucleoside analogs (lamivudine, adefovir, entacavir) Drug resistance, need for long-term treatment and expense are drawbacks
Hepatitis C Virus
- Emerging disease publicized in mid 90’s
- Originally termed “non A, non-B” hepatitis
- Leading cause of chronic hepatitis, 1.5% Americans seropositive for HCV
- 85% of those with exposure and acute infection develop chronic hepatitis
Hepatitis C Virus
-Transmission
transmitted parenterally, with primary means being injection drug use
Hepatitis C Virus
-Manifestations
- Incubation period is 6-12 weeks
- Acute infection is usually asymptomatic
Hepatitis C Virus
-Diagnosis
- diagnosed by testing for anti-HCV antibodies detectable within 6-8 weeks after exposure
- a positive test is confirmed by recombinant immunoblot assay (RIBA) or measuring HCV viral RNA
Hepatitis C Virus
-Treatment
Interferon and ribavarin are FDA licensed drugs for treating chronic HCV
Pegylated interferon-alpha plus ribavarin is drug of choice
Hepatitis Delta Virus
- RNA virus transmitted parenterally; can only replicate with the help of HBV
- The helical nucleocapsid uses HBV’s envelope HBsAg
HBV + HDV = BIG BAD DUDE
Hepatitis Delta Virus
-Co-infection
- HBV and HDV are both transmitted together parenterally and cause acute hepatitis
- antibodies to HBsAg is protective against both HBV and HDV
Hepatitis Delta Virus
-Superinfection
- HDV infects a person who has chronic HBV infection (like HBV carriers) resulting in acute hepatitis in a patient already chronically infected with HBV
- > Superinfection is severe with higher incidence of fulminant hepatitis, cirrhosis and greater mortality (5-15%)
- > Patients with chronic HBV cannot make anti-HBsAg and so remains chronically infected with both HBV and HDV
- Diagnosis is by the detection of delta antigen and antibodies to delta antigen
Hepatitis E Virus
- aka?
- transferred how?
- what does “E” stand for?
- HEV is often referred as “non-A hepatitis” as it shares similarities with HAV
- transferred by fecal-oral route
- “E” stands for Enteric. Endemic to Asia, India, Africa, and Central America
Hepatitis G Virus
- RNA or DNA?
- family?
- transmission?
- RNA virus in the Flavivirus family
- Transmitted by transfusion & parenternal routes
- Not conclusively shown to cause liver disease
