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Flashcards in Viral Hepatitis Deck (27):
1

Hepatitis A virus causes?

Hepatitis A

2

Important properties of Hepatitis A

* Typical enterovirus classified in the picornavirus family
* Single stranded RNA genome
* Non enveloped

3

Important properties of Hepatitis A

* Typical enterovirus classified in the picornavirus family
* Single stranded RNA genome
* Non enveloped icosahedral nucleocapsid & replicates in the cytoplasm
* Also known as enterovirus 72
* has one serotype
* No antigenic relationship to HBV or other hepatitis viruses

4

Transmission for Hepatitis A

*

5

Transmission for Hepatitis A

* Fecal-oral route, unlike HBV rarely transmitted via blood
* Humans are reservoir
* Virus appears in feces two weeks before symptoms so quarantine of patients is ineffective
* Children most recently infected
* Outbreaks occur in special living situations (summer camps, boarding schools)
* Common source outbreaks arise from fecaly contaminated water or food such as oysters grown in polluted water & eaten raw
* 50-75% of adults have been infected

6

Pathogenesis of Hepatitis A

* Not completely understood
* Probably replicates in GI tract & spreads to liver via blood
* Hepatocytes infected but mechanism by which cell damage occurs is unclear
* Hepatitis caused by different viruses can't be distinguished pathologically
* Immune response consists of IgM antibody which is detectable at the time jaundice appears
* IgM followed 1-3 weeks later by production of IgG antibody which provides lifelong protection

7

Clinical findings for Hepatitis A

* Hepatitis virus findings are virtually the same from all
* Fever, anorexia, jaundice, vomiting, nausea are typical
* Dark urine, pale feces, elevated transaminase levels
* Most cases resolve spontaneously in 2-4 weeks in contrast to Hep B which is 10-12 weeks
* Most asymptomatic & detectable solely by presence of IgG antibody
* No chronic hepatitis or carrier state occurs
* No predisposition hepatocellular carcinoma

8

Laboratory diagnosis for hepatitis A

.

9

Laboratory diagnosis for hepatitis A

* Detection of IgM antibody is most important test

10

Treatment for hepatitis A

* No antiviral therapy available
* Active immunization with a vaccine containing inactivated HAV available
* 2 doses, initial dose followed by booster 6-12 months later
* Vaccine recommended for travelers to developing countries, for children 2-18 yrs, and men-men sex
* If unimmunized person must travel to endemic area w/in 4 weeks then passive immunization should be given to provide immediate protection & the vaccine given to provide long term protection
* Many adults have

11

Treatment for hepatitis A

* No antiviral therapy available
* If unimmunized person must travel to endemic area w/in 4 weeks then passive immunization should be given to provide immediate protection & the vaccine given to provide long term protection
* Many adults have antibodies to HAV
* Passive immunization w/immune serum globulin prior to infection or w/in 14 days after exposure can prevent or mitigate the disease

12

Prevention for hepatitis A

* Active immunization with a vaccine containing inactivated HAV available
* 2 doses, initial dose followed by booster 6-12 months later
* Vaccine recommended for travelers to developing countries, for children 2-18 yrs, and men-men sex
* Observation of proper hygiene (sewage disposal, proper hand washing after bowel movements)

13

What disease does HBV cause?

HBV causes hepatitis B

14

Important properties of HBV

* Member of the hepadnavirus family
* 42 nm DNA enveloped virion
* Icosahedral nucleocapsid core containing partially double stranded circular DNA genome
* Envelope contains protein called surface antigen
* DNA Dependent DNA polymerase
* Genome contains 4 genes that encode 5 proteins
- S gene encodes surface antigen
- C gene encodes core antigen and e antigen
- P gene encodes polymerase
- X gene encodes x-protein (activator of viral RNA transcription)

15

What does the core antigen and e antigen do for HBV

Core antigen: Forms nucleocapsid core of virion
E antigen: Secreted from infected cells into the blood, important indicator of transmissibility

16

The specificity of HBV for liver cells is based on two properties

Virus specific receptors & transcription factors

17

Replicative cycle for HBV after entry of virion into cell and uncoating

1) Virion DNA polymerase synthesizes missing portion of DNA & a double stranded closed circular DNA formed in nucleus (This DNA serves as template for mRNA synthesis by cellular RNA polymerase)
2) After mRNAs are made a full length positive strand transcript is made which is a template for the minus strand of progeny DNA (Minus strand serves as template for plus strand of genome DNA)
This RNA-dependent DNA synthesis takes place in newly assembled virion core in cytoplasm

18

For HBV the RNA dependent DNA synthesis that produces the genome & the DNA dependent DNA synthesis that fills in the missing portion of DNA soon after infection of next cell are carried out by?

The same enzyme i.e. the HBV genome encodes only one polymerase

19

Replicative cycle for HBV after entry of virion into cell and uncoating

1) Virion DNA polymerase synthesizes missing portion of DNA & a double stranded closed circular DNA formed in nucleus (This DNA serves as template for mRNA synthesis by cellular RNA polymerase)
2) After mRNAs are made a full length positive strand transcript is made which is a template for the minus strand of progeny DNA (Minus strand serves as template for plus strand of genome DNA)
This RNA-dependent DNA synthesis takes place in newly assembled virion core in cytoplasm
3) Hepadnaviruses are the only ones that produce genome DNA by reverse transcription w/mRNA as template
4) Some progeny DNA integrates into host cell genome
5) Progeny HBV w/its HBs-Ag containing envelope is released from the cell by budding through cell membrane

20

For HBV the RNA dependent DNA synthesis that produces the genome & the DNA dependent DNA synthesis that fills in the missing portion of DNA soon after infection of next cell are carried out by?

The same enzyme i.e. the HBV genome encodes only one polymerase

21

Transmission by HBV

* 3 Main modes of transmission are: Blood via intercourse & parentally from mother to newborn (only small amounts of blood necessary) these are the natural routes
* Prevalent in addicts who use intravenous drugs
* Found worldwide especially Asia
* More than 300 million are chronically infected w/HBV & 75% are asian
* High incidence of hepatocellular carcinoma (hepatoma) in many asian countries
* Immunization against HBV has reduced incidence of hepatoma in children
* HBV vaccine is the first vaccine to prevent a human cancer

22

After HBV enters the blood the virus infects?

Hepatocytes & viral antigens are displayed on cell surface. Cytotoxic T cells mediate immune attack against viral antigens & inflammation & necrosis occur

23

About 5% of patients w/HBV infection become chronic carriers; in contrast, there is no prolonged carrier state in patients w/HAV infection. A chronic carrier is?

Someone who has HBsAG persisting in their blood for at least 6 months. Chronic carrier state is attributed to a persistent infection of hepatocytes which results in the prolonged presence of HBV & HBsAG in the blood
- high rate of heptaocellular carcinoma occurs in chronic carries
- Chronic carriage more likely to occur when infection occurs in newborns because of lowered immune system (90% become chronic carriers)
- Lifelong immunity occurs after natural infection & mediated by humoral antibody against HBsAG

24

Clinical findings for HBV

* Many asymptomatic & detected by presence of antibody to HBsAG
* Incubation 10-12 weeks
* Clinical appearance of acute Hep B similar to Hep A however is much more severe symptoms & life threatening hepatitis can occur
* Most chronic carriers are asymptomatic some have chronic hepatitis which can lead to cirrhosis and death

25

Treatment for HBV

* Alpha interferon clinically used for treatment of chronic hep B
* When drugs are stopped HBV replication resumes

26

Prevention for HBV

* Vaccine or immune globulin or both
* Vaccine contains HBsAG produced in yeasts by recombinant DNA techniques
* Vaccine is for people exposed to blood or blood products (health industry), patients receiving multiple transfusions or dialysis, patients w/frequent sexually transmitted disease , & abusers of illicit intravenous drugs

27

Prevention for HBV

* Vaccine or immune globulin or both
* Vaccine contains HBsAG produced in yeasts by recombinant DNA techniques
* Vaccine is for people exposed to blood or blood products (health industry), patients receiving multiple transfusions or dialysis, patients w/frequent sexually transmitted disease , & abusers of illicit intravenous drugs
* Travelers