Microbiology - Hepatitis viruses - Rebecca Greenblatt

Question 1

Phylogeny: Hepatitis A

Answer 1

Human-restricted 
naked 
picornavirus;
enterovirus 72;
RNA virus

Question 2

How is Hep A diagnosed?

Answer 2

Enzyme Immunoassay (EIA) for Anti-HepA IgM –> acute infection

EIA for Anti-Hep A IgG –> past infection, vaccination

Alanine aminotransferase (ALT) level: high –> ongoing liver damage

Question 3

Mode of transmission: Hepatitis A

Answer 3

Human to human

Question 4

Phylogeny of Hep E

Answer 4

\+ssRNA virus;
Small, 
naked
icosahedral;
hepeviridae

Question 5

Where is Hep E endemic?

Answer 5

China

Question 6

Mortality in pregnant patients is higher in Hep A or E?

Answer 6

E

Question 7

Mode of transmission: Hep E

Answer 7

fecal-oral

Question 8

Hep A and E are DNA or RNA viruses?

Answer 8

RNA

Question 9

Phylogeny: Hepatitis B

Answer 9

Hepadnavirus
DNA
Small, enveloped, partially double-stranded

Question 10

How many serotypes exist for Hep B?

Answer 10

Only one serotype, HBsAb protective against reinfection;

Effective vaccine available.

Question 11

Where in the body does Hep B replicate?

Answer 11

Liver hepatocytes, leaves behind integrated copies of viral DNA

Question 12

What is Heb B Surface antigen?

HBsAg

Answer 12

Surface Antigen appears early, ceases being detectable as surface antibody is produced, resumes being detectable in chronic

Question 13

What is Heb B Surface antibody?

Answer 13

Surface Antibody becomes detectable as surface antigen levels fall, raised by both vaccine and infection

Question 14

What is Hep B Core Antibody?

Answer 14

Core Antibody arises a little later, stays: IgM for acute, IgG for resolved or chronic infection – not raised by vaccine

Question 15

When is E antigen of Hep B detectable?

Answer 15

E Antigen detectable when virus most transmissible

Question 16

What causes the cirrhosis in Hep B?

Answer 16

Ongoing cytotoxic T-cell response against infected hepatocytes causes permanent cirrhosis – virus itself is not hepatotoxic

Accumulation of Hep antigen-antibody complexes leads to kidney damage & arthritis (membranous glomerulonephritis, mostly peds)

Question 17

What is the pathogenesis of Hep B cancer?

Answer 17

Virus genome integration, expression of viral transcriptional transactivators, and chronic inflammation can lead to cancer (primary hepatocellular carcinoma)

Question 18

How does Hep B look under the microscope?

Answer 18

“Ground-glass” cytopathology

Question 19

What is the treatment for Hep B?

Answer 19

1 year of polymerase inhibitors (lamivudine, adefovir entecavir, telbivudine)
PLUS
4 months of pegylated alpha-interferon (PEG-Intron, Pegasys) Significantly toxic, will cause heavy side effects (neutropenia, thrombocytopenia, disturbances of memory, concentration, vision, headaches, depression, irritability, hypo- or hyperthyroidism, nausea, vomiting, weight loss, alopecia, interstitial fibrosis)

Same drugs may be used to treat HepB-induced glomerulonephritis.

Question 20

What is Hep D?

Answer 20

Helper virus
NOT A COMPLETE VIRUS: a “defective” virus or “viriod”
Cannot replicate by itself, only in cells co-infected with HepB
1700 nucleotide circular -RNA “genome” encodes one protein: delta antigen

Question 21

Mode of transmission: Hep D

Answer 21

Blood and sex

Question 22

How does Hep D exacerbate Hep B?

Answer 22

Delta antigen IS cytotoxic
Dramatically increases the incidence of fulminant hepatitis
Affects ~5% of HepB carriers

Question 23

How is Hep D diagnosed?

Answer 23

Primary screening with EIA for anti-delta antibodies

Question 24

Phylogeny: Hep C

Answer 24

Human-restricted
Flavivirus
enveloped
+RNA genome

Question 25

Coinfection with Hep C is common with:

Answer 25

HIV

Question 26

Which virus, Hep B or C, has a higher potential for causing cancer?

Answer 26

Much higher potential for chronic infection than HepB, thus a stronger association with primary hepatocellular carcinoma (11-19%)

Question 27

Which hepatitis virus presents with the mildest initial infection?

Answer 27

Hep C - trying to stay under the immune radar

Question 28

What Hep C genotype is the most common in the U.S.?

Answer 28

Genotype 1

Question 29

How is Hep C diagnosed?

Answer 29

Serology: Liver function tests including ALT levels, albumin, bilirubin
EIA followed by RIBA
If positive, HCV genotyping
RT-PCR for viral RNA levels to assess success of therapy

Question 30

What are the goals of Hep C treatment?

Answer 30

Goal of treatment is sustained viral response (SVR) – like remission. “Failed” treatment may still reduce risk of hepatocellular carcinoma.

Question 31

What is the current Hep C treatment?

Answer 31

Simeprevir (inhibits protease) manufacturer claims can cure (not just SVR) serotype 1 by combined therapy with IFN and ribavirin

Sofosbuvir (inhibits polymerase) manufacturer claims can induce SVR in combined therapy with Ledipasvir (inhibits NS5A) without IFN or ribavirin

Sofosbuvir in combination with ribavirin is active against Genotypes 2&3

Question 32

Where is Hep A endemic?

Answer 32

A is endemic in Mexico and South America

Question 33

Where is Hep E endemic?

Answer 33

Asia and Mexico

Question 34

What is the second generation treatment for Hep C?

Answer 34

Second-generation protease inhibitors combined with IFN improve SVR rates for HepC serotype 1

Question 35

What is the basic pathogenesis of Hep B, if it is not asymptomatically cleared?

Answer 35

B produces a large number of immune decoys composed of its surface antigen alone. Antigen-antibody complex disease may follow (ex glomerulonephritis)