Buxton 1-7-08 Viral Hepatitis

Front 1

Hepatitis A Virus

Family: _______viridae; ______virus group; _NA virus

Back 1

Hepatitis A Virus

Family: Picornaviridae; Enterovirus group; RNA virus

Front 2

Transmission of Hep A

Back 2

Fecal/Oral

Front 3

hep A Never produces a chronic carrier state, T or F

Back 3

hep A Never produces a chronic carrier state, True

Front 4

Incubation period of hep A

Back 4

30 days avg (15-50 days)

Front 5

jaundice by age group with Hep A

<6yrs, ___%
6-14 yrs, _____%
>14yrs, _____%

Back 5

jaundice by age group with Hep A

<6yrs, <10%
6-14 yrs, 40-50%
>14yrs, 70-80%

Front 6

Dx of hep A

Back 6

2-6 weeks: virus in feces and liver biopsy
> 4 weeks: HAV IgM (peak 5wks)
> 5 weeks: HAV IgG (peak 8wks)

Front 7

icterus?

Back 7

jaundice

Front 8

hep A symptoms?

Back 8

icterus, elevated serum liver enzymes

Front 9

2 activities of DNA polymerase of HBV

Back 9

DNA-dependent DNA olymerase activity

Reverse transcriptase activity

Front 10

HBV
Family _______viridae; _NA virus
NA replication includes RNA intermediate that serves as template for progeny DNA strands- requires reverse transcriptase
Thus, ___s are used as anti-viral
Transmitted in _____ and body fluids
Causes acute and chronic infections (age)

Back 10

HBV
Family Hepadnaviridae; DNA virus
NA replication includes RNA intermediate that serves as template for progeny DNA strands- requires reverse transcriptase
Thus, RTIs are used as anti-viral
Transmitted in blood and body fluids
Causes acute and chronic infections (Age)

Front 11

90% of the time, neonates exposed to HBV get a _______ infection

Back 11

90% of the time, neonates exposed to HBV get a Chronic infection

Front 12

Adults have a ____% chance of chronic HBV infection

Back 12

Adults have a 5-10% chance of chronic HBV infection

Front 13

Incubation period for HBV is ___ days and is infectious during that time.

compare this with Goljan

Back 13

Incubation period for HBV is 100 days and is infectious during that time.

compare this with Goljan

Front 14

Hep B virus is low or undetectable in what substances

Back 14

urine, feces, sweat, tears, breast milk

Front 15

Bad outcome of chronic HBV infection

Back 15

cirrhosis and liver cancer

Front 16

How long does it take HBsAb to form

Back 16

32 weeks

Front 17

Treatment of chronic HBV

Back 17

Interferon alpha
PEG Interferon*
(PEG slows down breakdown of IFN)
Nucleoside/nucleotide reverse transcriptase inhibitors
Lamivudine
Adefovir*
Entecavir*
Telbivudine

*Recommended as first-line choices for monotherapy by AASLD

Front 18

Treatment Guidelines

HBeAg-positive patients:
HBV DNA < 20,000 IU/ml, ______ ALT- monitor but do not treat
HBV DNA > 20,000 IU/ml AND ________ ALT- treat
HBV DNA > 20,000 IU/ml and ______ ALT- consider biopsy to assess degree of liver damage
HBeAg-negative patients (see slide notes):
As above, except lower cutoff for HBV DNA (2000 IU/ml)

Back 18

Treatment Guidelines

HBeAg-positive patients:
HBV DNA < 20,000 IU/ml, normal ALT- monitor but do not treat
HBV DNA > 20,000 IU/ml AND elevated ALT- treat
HBV DNA > 20,000 IU/ml and normal ALT- consider biopsy to assess degree of liver damage
HBeAg-negative patients (see slide notes):
As above, except lower cutoff for HBV DNA (2000 IU/ml)

Front 19

HBeAg-negative patients with evidence of liver damage may be infected with what?

Back 19

HBeAg-negative patients with evidence of liver damage may be infected with mutant virus that is unable to make HBeAg, yet able to replicate as well as wildtype. This mutant has been associated with poor outcome if untreated.

Front 20

What is MOA of IFN-alpha

Back 20

Increases MHC-I expression on infected cells, thereby enhancing CD8 cytotoxicity
Also stimulates T cells and NK cells

Front 21

adverse effects of IFN-alpha

Back 21

Flu-like symptoms
Bone marrow suppression
Depression and other psychiatric disorders
Exacerbation of autoimmune disorders

Front 22

RTI MOA:
Interfere with reverse transcriptase activity essential to replication of HBV ___
Very few adverse affects
Problem with acquired drug resistance
20% of patients develop resistance to l_________ after 1 yr

Back 22

Interfere with reverse transcriptase activity essential to replication of HBV DNA
Very few adverse affects
Problem with acquired drug resistance
20% of patients develop resistance to lamivudine after 1 yr

Front 23

Passive HBV vaccination is used to prevent infection after exposure in:
WHo?

Back 23

Passive HBV vaccination is used to prevent infection after exposure in:
Infants born to infected mothers
Spouces of infected patients
HCW following needle stick injury

Front 24

Active HBV vaccine

Recombinant vaccine
Consists of HBsAg produced by _____ transfected with gene for surface antigen
Recommended for all newborns
“Catch up” vaccination of adolescents and high risk adults

Back 24

Active HBV vaccine

Recombinant vaccine
Consists of HBsAg produced by yeast transfected with gene for surface antigen
Recommended for all newborns
“Catch up” vaccination of adolescents and high risk adults

Front 25

HBV vacc

3 dose series, typical schedule 0, ___, ___ months - no maximum time between doses (no need to repeat missed doses or restart)

Back 25

HBV vacc

3 dose series, typical schedule 0, 1-2, 4-6 months - no maximum time between doses (no need to repeat missed doses or restart)

Front 26

Hepatitis D Virus
Modes of Transmission

Back 26

Percutanous exposures
injecting drug use
Permucosal exposures
sex contact

Front 27

HDV requires _____ to replicate

Back 27

HDV requires HBsAg to replicate

Front 28

Hepatitis D - Clinical Features

Coinfection:
severe acute disease
low risk of _______ infection

Superinfection:
usually develop ______ HDV infection
high risk of severe chronic liver disease

Back 28

Hepatitis D - Clinical Features

Coinfection
severe acute disease
low risk of chronic infection
Superinfection
usually develop chronic HDV infection
high risk of severe chronic liver disease

Front 29

Any measure to prevent ___ will prevent HDV co-infection- ie vaccination

Back 29

Any measure to prevent HBV will prevent HDV co-infection- ie vaccination

Front 30

How is superinfection of HBV-HDV prevented

Back 30

Education to reduce risk behaviors among persons with chronic HBV infection

Front 31

hep C:

_NA virus in family _____viridae

Back 31

hep C:

RNA virus in family Flaviviridae

Front 32

Hep C develops into chronic case in > __% of cases

Back 32

Hep C develops into chronic case in > 70% of cases

Front 33

hep C:

_____species reflect genetic variants arising within infected individuals

Back 33

hep C:

Quasispecies reflect genetic variants arising within infected individuals

Front 34

Estimated percentage of US poulation has Hep C?

Back 34

2%

~4 million people presently infected

Front 35

Persons with hemophilia treated before 1987 -- __%
Current IV drug users -- __%
Persons with abnormal ALT levels -- __%

Back 35

Persons with hemophilia treated before 1987 -- 87%
Current IV drug users -- 79%
Persons with abnormal ALT levels -- 15%

Front 36

Risk Factors for HCV Infection

Back 36

IV drug use
Multiple sex partners

Front 37

Diagnostic Tests for HCV

Back 37

Serologic:
ELISA
RIBA

Virologic (RT-PCR):
Qualitative HCV-RNA
Quantitative HCV-RNA

Front 38

Initial diagnosis HCV,
screening test

Back 38

Anti-HCV
ELISA


Can be positive within
several weeks of exposure

Front 39

Confirms
ELISA results

Back 39

HCV RIBA


Useful in low-risk
populations (eg, blood
donors)

Front 40

percent of HCV pts with asymptomatic infection

Back 40

75%

Front 41

Assesses HCV viral load

Back 41

HCV PCR
quantitative

Front 42

what Should be done prior to initiation of HCV treatment

Back 42

Genotype test

Front 43

Sign of chronic HCV

Back 43

elvated ALT with anti-HCV-IgG

Front 44

Immune Response to HCV

Antibody and T cells demonstrated against all viral proteins
Ability to clear virus may depend on efficacy of T cell response (CD4 and CD8 cells)
Genetic variants (Quasispecies) arise rapidly, escape immunologic control
Liver injury due to ___________ ______ _____ _______

Back 44

Immune Response to HCV

Antibody and T cells demonstrated against all viral proteins
Ability to clear virus may depend on efficacy of T cell response (CD4 and CD8 cells)
Genetic variants (Quasispecies) arise rapidly, escape immunologic control
Liver injury due to inflammatory cells and cytokines

Front 45

Genotypic Variation:
Genotypes vary in sensitivity to interferon
Genotype _ is most resistant and most common in US
Genotype may affect duration of treatment (6 vs 12 months)
Resistance mapped to the __ non-structural gene region (NS5A)

Back 45

Genotypic Variation:
Genotypes vary in sensitivity to interferon
Genotype 1 is most resistant and most common in US
Genotype may affect duration of treatment (6 vs 12 months)
Resistance mapped to the 5A non-structural gene region (NS5A)

Front 46

Risk of Neonatal Transmissionof HCV

<_% risk
Higher if co-infected with HIV
Risk correlates with viral load
No evidence of transmission via ______ ____

Back 46

Risk of Neonatal Transmissionof HCV

<5% risk
Higher if co-infected with HIV
Risk correlates with viral load
No evidence of transmission via breast milk

Front 47

Predictors of Treatment Success

Young age
_(sex)__
Lesser degree of liver fibrosis
Viral load <2 million copies per mL
Genotype other than _

Back 47

Predictors of Treatment Success

Young age
Female
Lesser degree of liver fibrosis
Viral load <2 million copies per mL
Genotype other than 1

Front 48

Major Side-Effects of Interferon

___-like symptoms
Depression
Difficulty concentrating
Bone marrow suppression

Back 48

Major Side-Effects of Interferon

Flu-like symptoms
Depression
Difficulty concentrating
Bone marrow suppression

Front 49

Major Side-Effects of Ribavirin

T________icity
A______
__ upset
Sore throat, cough, dyspnea
Skin ____

Back 49

Major Side-Effects of Ribavirin

Teratogenicity
Anemia
GI upset
Sore throat, cough, dyspnea
Skin rash