L 84-85 Viral Hepatitis

Question 1

Which hepatitis viruses are transferred fecal-oral?

Answer 1

A and E
The vowels are in the bowels
Also naked and more resistant to drying and dessication and environmental factors

Question 2

Which hepatitis viruses are blood-borne?

Answer 2

B, C, D

All enveloped and more fragile or sensitive to insult

Question 3

Hep A virus

Characteristics

Answer 3

Picornaviridae
(+) sense naked RNA
Highly resistant to harsh conditions–lacking envelope
Capsid proteins bind receptors in hepatocytes

Question 4

Hep A epidemiology

Answer 4

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

Question 5

Hep A clinical features

Answer 5

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

Question 6

HAV Pathogenesis

Answer 6

Fecal-Oral
Internalized by hepatocytes and replicates
Viral particles released into bile then GI
Causes non-permanent liver damage

Question 7

HAV outcome

Answer 7

Mild disease with complete recovery in almost all cases

Infection not chronic, life-long immunity

Question 8

Hep E virus

Answer 8

(+) sense naked ssRNA

No envelope

Question 9

Hep E epidemiology

Answer 9

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

Question 10

Hep E clinical features

Answer 10

Very similar to Hep A
Abrupt onset
Higher mortality than A especially in pregnant women

No long-term issues

Question 11

HEV diagnosis

Answer 11

Elevated anti-HEV IgM corresponding with onset of symptoms

IgG later and lasts >6 months

Question 12

HEV treatment/prevention

Answer 12

Symptomatic treatment

Proper sanitation, vaccine in development

Question 13

Hep B virus

Answer 13

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

Question 14

Hep B replication

Answer 14

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.

Question 15

Hep B epidemiology

Answer 15

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

Question 16

Hep B Clinical Features

Answer 16

Acute and Chronic hepatitis
Subclinical and Icteric disease
90% recover within 3-6 months, rapid liver necrosis, 5% chronic

Question 17

HBV pathogenesis

Answer 17

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

Question 18

HBV diagnosis

Answer 18

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

Question 19

Hep D virus

Answer 19

(-) sense ssRNA, very simple circular RNA
Requires Hep B to complete life cycle
Has HDAG inside HBsAG envelope

Question 20

HDV replication

Answer 20

RNA copied by Host RNA pol II and makes mRNA => delta antigen that gets packaged in HBsAG and then released

Question 21

HDV epidemiology

Answer 21

Worldwide

Question 22

HDV clinical features

Answer 22

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

Question 23

HDV Pathogenesis

Answer 23

Virus enters hepatocytes, requiring HBV infection to replicate
Replication and CMI response cause the symptoms

Question 24

Hep C virus

Answer 24

(+) sense enveloped ssRNA

Question 25

Hep C replication

Answer 25

Binds to LDL molecules that help guide to hepatocytes
SR-B1 and CD81 allow endocytosis
Replication in cytoplasm

Question 26

Hep C epidemiology

Answer 26

Six main genotypes
Worldwide distribution
Transmitted through contact with contaminated blood
Transplants, transfusion, IVDU, cocaine use
Adults more than kids

Question 27

HCV clinical

Answer 27

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

Question 28

Why does HCV often become chronic?

Answer 28

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