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Flashcards in Viral Hepatitis Deck (42):
1

What family and genus does HAV belong to?

Picornaviridae and Enterovirus

2

What is the structure of HAV?

Nonenveloped icosahedral capsid ss RNA (+) (less than 7 kb)

Single serotype

3

What family and genus does HEV?

Family Caliciviridae and Hepevirus

4

What is the structure of HEV?

Nonenveloped icosahedral capsid 7.5 kb ss RNA (+)

Single serotype

5

What are the reservoirs of HAV? HEV?

 

HAV: Humans

HEV: Possible swine, mostly prevalent in developing countries, only causes FLF in pregnant women

6

Describe the pathogenesis of HAV

It is contracted via a fecal-oral route, with replication occuring in the GI tract during the ~2 week incubation period. Contraction is most common early disease

7

How does HAV present?

Often asymptomatic with symptoms including anorexia, malaise, fever, HA, and possibly jaundice over a 4-5 week period

8

What groups are at risk fo HAV?

-Household or sexual contacts

-Travelers to endemic areas

-Inhabitants of American Indian reservations

-During outbreaks: Diners, Day care center workers, Gay men, Injecting drug users

9

How is HAV diagnosed?

-Presumptive diagnosis on appearance and history

-Detection of anti-HAV IgM

10

What vaccine options are available for HAV?

-Passive immunization with gamma globulin

-Inactivated vaccine (Havrix) in those 2 years of age or older

-Combination vaccine for HAV and HBV (Twinrix): Havrix plus recombinant HBV vaccine. Only for those 18 years of age or older

-Vaccine or gamma globulin is recommended for travelers to endemic areas

11

Hepatitis Virus Nomenclature

HAV: ET-hepatitis

HBV: PT-hepatitis

HCV: “nonA, nonB” PT-hepatitis

HDV: dependent on HBV for infection

HEV: “nonA, nonB” ET-hepatitis

12

Describe the structure of HBV?

Hepadnavirus

Enveloped virus termed Dane particle

Partially ds DNA genome, 3200 bp

Structure: Circular coat protein (HBsAg) surrounded circular core (HBcAg) containing DNA genome and polymerase

13

What are the 5 major proteins of HBV?

DNA polymerase (reverse transcriptase)

HBsAg: surface antigen, attachment protein (Mostly found in 20 nm particles and filaments)

-HBcAg: core antigen, capsid protein

-HBeAg: derivative of HBcAg, important serolgic marker

-X antigen: influences gene expression

14

How does HBV replicate?

Fusion endocytosis followed by uncoating of the core, completion of ds DNA genome and then entry into the nucleus for transcription. Translation occurs in the cytosol via reverse transcriptase to produce a partial ds DNA genome, which is then mostly maintained extrachromosomally in chronic infections

15

Where is HBV most common?

-Endemic to China and sub-Saharan Africa

-Late infection in US and Europe

 

16

How is HBV transmitted?

Virus is present in blood, semen, and vaginal secretions

Transmission is by parenteral route

-Injection drug use

-Sexual intercourse

-Perinatal at delivery

17

What does a positive HBsAg suggest?

carrier or acute infection of HBV

18

What does a positive Anti-Hb Ab suggest?

a pt has had HBV or received vaccine

19

What does a positive HBeAg suggest?

these pts are at an increased risk of transmission  (positive Anti-HBe is used to ID HBsAg carrier with low risk of transmission)

20

What does a positive Anti-HBc suggest?

ID of persons with past infection

21

What does a positive IgM Anti-HBc suggest?

ID of acute or recent infection

22

Describe HDV

-Encodes delta antigen, its core protein

-Enveloped, circular ss RNA genome of 1.7 kb

-HDV particles must incorporate HBsAg to infect hepatocytes

23

What is the family of Hep C?

Flavivirdae

24

Describe the structure of Hep C

-Hepacivirus

-Enveloped icosahedral capsid

-9.4 kb ss RNA (+) genome

25

What are the genotypes of HCV?

-6 major genotypes, further divided into subtypes

-1a, 1b, 2a, 2b are worldwide

-1a and 1b are most common in US

-Patients also contain quasi-species

26

Where is HCV most common?

Highest incidence in Asia, Middle East and Nort Africa with incidence dropping in the US

27

What are the risk factors of contracting HCV?

Born between 1945-1965 (80% of chronic cases)

Illicit (injection) drug use

Perinatal infection at birth

Prison

28

T or F. Acute infections of HCV are milder than HBV

T.

29

How does the immune system affect hepatitis?

Hepatitis viruses are not cytolytic

Immune destruction (cytotoxic T cells) of infected hepatocytes leads to liver disease

30

What most commonly causes chronic hepatitis?

-40% of cases are due to HCV

-20% due to HBV

-5% contain HDV

-Remainder of unknown origin

31

The development of chronic HBV depends heabvily on what?

the age of initial infection

< 1 yo: 90% chronicity rate

1-5 yo: 30% rate

> 5 yo: 2% rate

32

How deadly is chronic HBV?

25% mortality, most commonly in the 60s

33

What are the stages of chronic HBV?

-Immune tolerance phase

-Immune clearance phase

-Residual phase

34

What are the major outcomes of acute Hep B?

90% resolve, 1% lead to fulminant hepatitis, and 9% progressive to chronicity (HBsAg+ for 6+ mos)

35

What are the major outcomes of chronic Hep B?

50% resolve

-asymptomatic carrier state

-chronic persistant hepaitis or chronic acute hepatitis leading to cirrhosis, HCC, and/or extrahepatic disease

36

What are the major outcomes of untreated acute HCV?

15% resolve

85% on untreated will lead to chronic infection leading to liver failure, cirrhosis, or HCC

37

Notes

 

Immunize HBV and HCV chronic patients against HAV

Discourage alcohol use

HBV and HCV liver disease is the leading reason for liver transplants

Despite HBV vaccine, HBV-related cancers and deaths have doubled in the past decade

38

Diagnosis of Hep at presentation

1) Acute forms of ET- and PT-hepatitis can be similar

2) Determine Source of infection and ELISA

-HBV: HBsAg, anti-HBc IgM; HBeAg, HBe antibody, HBV DNA

-HCV: anti-HCV antibodies, HCV RNA

3) Determine HCV genotype

39

HBV control

Screen blood supplies for HBsAg, HBc antibodies, HBV DNA

Vaccines

-(Plasma-derived HBsAg)

-Yeast expressed HBsAg

-Twinrix

-Childhood immunization recommended

HBIg for exposed individuals

-Newborns

-Can be used prophylactically for travelers

40

What is the goal of HBV antivirals?

Goal is to reduce the risk of progressive chronic disease, transmission, and complications (cirrhosis, HCC)

41

What are some indications to initiate HBV antiviral therapy?

>2000 units/mL HBV DNA

>2x upper normal limit of serum ALT

42

HCV Control

Screen blood supplies for antibodies to core antigen, HCV RNA

-No vaccine in US yet, no passive immunization

-“HCV is relatively easily treated and can be eliminated in almost all patients.”

-Thus, goal of therapy is to eliminate HCV RNA

-Treatment varies by genotype