L 84-85 Viral Hepatitis Flashcards
Which hepatitis viruses are transferred fecal-oral?
A and E
The vowels are in the bowels
Also naked and more resistant to drying and dessication and environmental factors
Which hepatitis viruses are blood-borne?
B, C, D
All enveloped and more fragile or sensitive to insult
Hep A virus
Characteristics
Picornaviridae
(+) sense naked RNA
Highly resistant to harsh conditions–lacking envelope
Capsid proteins bind receptors in hepatocytes
Hep A epidemiology
Fecal-Oral
Shed 2 weeks before symptoms–oral to intestines to blood to liver to bile to stool
Common in restaurants, daycare, shellfish, food, water
Endemic in countries with overcrowding and lower hygiene
Vaccine has drastically lowered incidence
Hep A clinical features
Acute hepatitis
Abrupt onset of Sx
Incubation 2-4 weeks
IgM to IgG change with time by gamma interferon from Th1 cells
Initial: fever, fatigue, abd pain, hepatomegaly
Later: dark urine, pale stool, jaundice, pruritis
Sx last 4-5 weeks
HAV Pathogenesis
Fecal-Oral
Internalized by hepatocytes and replicates
Viral particles released into bile then GI
Causes non-permanent liver damage
HAV outcome
Mild disease with complete recovery in almost all cases
Infection not chronic, life-long immunity
Hep E virus
(+) sense naked ssRNA
No envelope
Hep E epidemiology
Fecal-oral spread
Clinical disease mimics Hep A
Higher fatality than A
Four known genotypes mostly based by locations in the world
Most common in developing countries with inadequate water supply and sanitation
Overall uncommon in USA
Hep E clinical features
Very similar to Hep A
Abrupt onset
Higher mortality than A especially in pregnant women
No long-term issues
HEV diagnosis
Elevated anti-HEV IgM corresponding with onset of symptoms
IgG later and lasts >6 months
HEV treatment/prevention
Symptomatic treatment
Proper sanitation, vaccine in development
Hep B virus
Enveloped, partially dsDNA virus
S gene: HBsAG (L, M, S glycoproteins)
C gene: HBcAG (core), HBeAG (core + PreC)
P gene: DNA polymerase, reverse transcriptase
X gene: Transcriptional transactivators that aid viral replication
Hep B replication
dsDNA completed by viral DNA polymerase to form cccDNA that is then transcribed by host RNA polymerase to form four mRNAs. The longest is reverse transcribed by viral reverse transcriptase into (-) DNA that serves as a template for creation of partial (+) DNA that becomes the new DNA of newly formed viruses and can also feedback to amplify the replication going on in the nucleus
Released into the blood is not only fully active viruses, but also empty shells called spheres and filaments that are HBsAG.
Hep B epidemiology
Blood-borne transmission and sexual contact, IVDU most common
Mother to baby at birth
Blood transfusion now low risk
Younger kids tend to have a chronic infection because of immature immune system
World-wide distribution
Hep B Clinical Features
Acute and Chronic hepatitis
Subclinical and Icteric disease
90% recover within 3-6 months, rapid liver necrosis, 5% chronic
HBV pathogenesis
Enters blood, goes to liver and replicates
Immune response needed for resolution, but also causes hepatic damage
Effective CMI response => resolution
Ineffective CMI => chronic disease, cirrhosis
HBV diagnosis
Acute: HBsAG and HBeAG first indicators of infection before onset of symptoms, don’t see anti-HBs early on because they are bound to antigen
Chronic: absence of anti-HBs
Hep D virus
(-) sense ssRNA, very simple circular RNA
Requires Hep B to complete life cycle
Has HDAG inside HBsAG envelope
HDV replication
RNA copied by Host RNA pol II and makes mRNA => delta antigen that gets packaged in HBsAG and then released
HDV epidemiology
Worldwide
HDV clinical features
Coinfection D & B: likely to recover and be immune to both, possibly more severe than HBV alone during course of disease
D superinfection: infection of B carrier, often leads to chronic infection and fulminant hepatitis, cirrhosis, hepatic encephalopathy, and massive hepatic necrosis
HDV Pathogenesis
Virus enters hepatocytes, requiring HBV infection to replicate
Replication and CMI response cause the symptoms
Hep C virus
(+) sense enveloped ssRNA
Hep C replication
Binds to LDL molecules that help guide to hepatocytes
SR-B1 and CD81 allow endocytosis
Replication in cytoplasm
Hep C epidemiology
Six main genotypes
Worldwide distribution
Transmitted through contact with contaminated blood
Transplants, transfusion, IVDU, cocaine use
Adults more than kids
HCV clinical
Acute and Chronic (like B)
Most cases become chronic–most common cause of liver transplant in US
Acute: insidious onset, similar to HAV and HBV
Chronic: most become chronic, similar to HBV chronic, but double the fatality rate
Why does HCV often become chronic?
Blocks IFN type I and II that blocks the JAK-STAT pathway to block the signaling to other cells to start fighting the infection
Blocking production of antiviral cytokines like IFN-gamma
Blocks production of ISG (interferon stimulating genes) proteins responsible for suppressing HCV replication
