T2 - Micro - Virology 2 - Hepatitis

Front 1

what basic lab tests and definitions do we see in hepatitis? what can cause hepatitis?

Back 1

see damage to hepatocytes and inflammatory cells in the liver.

also see rises in AST and ALT.

can have acute (lasting less than six months, can be severe or not).

can have fulminant (quickly developing, lasting short time, high mortality)

chronic - lasting more than six months - maybe/maybe not severe.

can be caused by viruses, toxins, bacteria, ameobes, drugs, autoimmune problems, inborn metabolic disorders.

Front 2

what are typical symptoms seen in hepatitis?

Back 2

flu stuff, nausea vomiting, fever, diarrhea, light colored stools, dark urine, jaundice.

Front 3

Hepatitis B - what does it look like, what is its nucleic acid, approximate size? What forms can it come in?

Back 3

large, 42nm particle = DANE particle.

Has Double-Stranded DNA (it's the only hepatitis virus that has DNA instead of RNA). Icosehedral matrix.

note that it's PARTIALLY circular dsDNA - there's a chunk of one strand missing.

also can come in a filamentous form, consisting largely of surface protein (HBsAg). This, I think, is the AUSTRALIAN ANTIGEN?

Dane particle is the whole viron.

Front 4

Life cycle of Hep B: what's one really weird step?

Back 4

unknown receptor, fusion, uncoating.

Don't forget that it's an incomplete dsDNA - so it has to go to nucleus to get the rest of one strand.

This forms CCC (covalently closed circular DNA).

Then transcribed into mRNA and pregenomic RNA (pgRNA).

Assembly with the pgRNA inside.

then, REVERSE TRANCRIPTION into viral DNA.

Enveloped in ER and bud off.

This reverse transcription step is weird for a DNA virus - called "pararetroviridae"

Front 5

what are the Hep B antigens we're interested in?

Back 5

surface antigen (HBsAg)

core antigen (HBcAg)

and HBeAg (a soluble part of the capsid).

SEC.

Front 6

What's up with HBsAg? Why make it?

Back 6

the weird little filamentous rod things are full of it.

It's likely an antibody sponge - a decoy - sucking up excess antibodies that would otherwise fight off the virus.

Note that the host response can be dangerous - autoimmnune diseases possible..

Front 7

How does HBV cause disease?

Back 7

no direct cytopathic effects of the virus - seems to be immune driven.

specifically cell mediated killing.

antigens are targets for CD8 cells, too bad these antigens are inside hepatocytes.

Also, immune complexes have been seen in fulminant patients, but not those with chronic/acute disease.

Front 8

what body fluids can hep B live in?

also, what's the average incubation period? if someone's infeted and has acute hepatitis B, what are the probablities of disease progression?

Back 8

all of them.

Blood, serum, wounds have the most.

Semen/vaginal/saliva have nexgt most.

Urine/feces/sweat/tears/milk have less.

average incubation period is 60 to 90 days.

if infected and acute -

90% resolve on thir own, clear. 1% are fulminant and screwed.

the other 9 percent become chronic. Half of them will clear the virus and be fine.

The other half is divided between chronically persistant (with non-liver probmems like polyarteritis nodosum and glomerulonephritis, the other ones have cirrhosis and HCC).

Front 9

What kind of caner does HBV increase the risk of?

Back 9

hepatacellular carcinoma (HCC).

people with HBV detectable DNA are 4x more likely to get it. More DNA present = more risk of cancer.

Front 10

is there just one kind of HBV?

Back 10

no - 8 genotypes (a through h).

note that type C is more likely to cause cancer. geographical distributions different.

Front 11

describe the antigens and antibodies present in hepatits B infection and what they means

Back 11

HBsAg - this is the surface antigen protein. First antigen to come up during infection. General infection marker, if it lasts more than 6 months = chronic infection.

Anti-HBsAb - this is a good thing. Means recovery from or immunity to HBV. Detectable in people who have gotten the vaccine but never the disease. Sometimes in chronic carriers, rarely.


HBeAg - marker of active replication - people with it are thought to be highly infectious, not a good thing to have. If you have Anti-HBeAb, this is good - virus is NO LONGER REPLICATING and probably on the way to resolution.

Anti-HBcAg(total) - this sticks around forever, lifelong marker of infection (think c = cancer = forever). either acute or chronic.

Front 12

talk about the antibody/antigen profiles of someone clearing HBV

Back 12

recovering:

as always, HBsAg comes up first, followed almost immediately by HBeAg. Recall that if you're clearing the virus, Anti-HBsAb appears - though this happens AFTER HBsAg disappears on its own. This is the "HBsAg WINDOW" - no antibody OR antigen.

Only detectible thing during this period is Anti-HBcAg - recall that this is our lifelong marker of infection. So it's hard to tell how the disease is progressing during this time period.

Toward the end, you see Anti-HBsAg come up - this is found only in people who have cleared the bug from their system.


Anti-HBeAg eventually comes up and sticks around.

note that these are all measured from the onset of jaundice/other liver symptoms

Front 13

antibody/antigen profile of someone with chronic HBV?

Back 13

Again, HBsAg starts off first, followed quickly by HBeAg - note though that you never get Anti-HBsAb's made - this would mean you've cleared the virus (you're chronic). note that the definition of chronic infection is having HBsAg levels up for over 6 months.

HBsAg stays up. HBeAg eventually wains.

Anti-HBcAg again comes up early and stays up for the entire life (life long marker).

After years, see Anti-HBeAg pop up and stay up.

In both cases, liver enzymes spike early and then drop off.

Front 14

other than serum tests, what other tests can we look at to evaluate the progression of disease?

Back 14

HBV DNA tests. If there's detectable DNA after six months of acute symptoms, you're chronic.

Can differentiate between a resolved case and a carrier (carriers have less than 2000 IU/Ml, those resolved are undetectable).

Can also watch the DNA level to see how therapy is working out (increases during resistance, goes down during working therapy).

Correlates with disease progression.

Front 15

Available treatments?

Back 15

Peg-interferon, works really only when the host has a working immune system. If immunotolerant of virus, no effect.

Nucleoside analogues - works best when virus is replicating..

Also, liver transplantation.

Front 16

Vaccine?

Back 16

yes - recombinant vaccine available. Induces production of HBsAb's, providing permanent protection.

Front 17

What's hepatitis D?

Back 17

Delta virus - REQUIRES CONCURRENT HBV INFECTION TO REPLICATE.

It's circular, ssRNA negative stranded. Needs host RNApolII. Delta antigen.

IV drug use and sex acquired.

Prevent by preventing HepB.

Diagnosed by presence of delta antigen.

Front 18

what family is HepB in?

Back 18

Hepadnaviridae.

it has DNA in the name, and it's the only hep virus that has DNA in the name.

Front 19

Talk about the clinical outcome of HBV infection - probablities that you get chronic infection, etc

Back 19

90% of those infected resolve on their own, no more story.

1% immediately get fulminant bad news hepatitis.

the other 9% have HBsAg's that are positive for >6 months and are, by definition, chronic.

so 10% of people infected become chronic (9, actually).

of those, half resolve.

the rest either become carriers, chronic for long times, or get active disease (including HCC)

so 5% end up with not so good outcomes.

Front 20

Hepatitis C - what family is it in? What does it physically look like? Genetics?

Back 20

Flaviridae family.

It's ssRNA, (+) sense. Enveloped.

Has one big ORF that has to be cleaved before packaging.

Front 21

describe the life cycle and replication - what's one thing to remember about its replication here?

Back 21

remember, it's a ssRNA + stranded virus.

Endocytosis and vessicle fusion like normal, then movement to rough ER (+ stranded RNA viruses can act like mRNA).

Replication involves changing from + to -, back to +. Has a dsRNA intermediate.

HepC lacks an RNA polymerase proofreading activity! So, there are lots of hypervariable regions and QUASISPECIES.

Front 22

what's the incubation average for HepC? What does acute infection look like?
what causes tissue damage?

Back 22

Averages 6 to 7 weeks.

Just like HepB and most viruses, the acute phase is generally asymptomatic (so most replication/infectivity is before you show symptoms).



again, not directly cytopathic virus - disease happens because of immune activation (cell mediated mostly).

in fact, the amount of lymphocytic infiltration into the liver can be a marker of disease progression.

Front 23

what precedes the onset of HCC?

Back 23

fibrosis and then cirrhosis.

Front 24

what are the possible outcomes of HepC infection and what percentages experience what?

Back 24

only 15% recover/clear the virus without getting sick.

15% also proceed directly to cirrhosis and rapid onset disease.

The remaining 70% are infected. Of those, 40% are asymptomatic forever.

The remaining 30% have chronic hepatitis C. Of those, 6% get liver failure, 20% get cirrhosis, and 4% get HCC.

Front 25

what makes HepC worse?

Back 25

being HIV infected

drinking booze.

using pot every day.

being >40 at infection time.

male gender. ALso, having HBV is bad news too at the same time.

Front 26

can babies get HepC from mom?

Back 26

yes - only if HCV RNA is detectable during birth. `

Front 27

lab diagnoses of HepC?

Back 27

ELISA is screen.

RIBA is confirmatory (recombinant immunoblot assay).

NAT.
real time PCR to quantitate.

Front 28

talk about the serological patterns of those with cleared HepC and those who are chronically infected

Back 28

those who clear:

during symptomatic phase, ALT rises then eventually goes back to zero.

Same with detectable HCV RNA - it appears during symptoms, then goes away completely.

Note that Anti-HCV ab's come up and stay up forever.

CHRONICALLY INFECTED:

Note that ALTs come up, drop, come up, drop...they bounce around all the time.

ALSO - IMPORTANT - HCV RNA comes up and STAYS UP, with SMALL GAPS in between (so one negative test DOES NOT MEAN THAT YOU ARE CLEAR!).

Anti HCV-ab's come up the same way and stay up - so your antibody production here doesn't mean much of anything, other than that you've been infected.

Front 29

how do we treat HCV? Vaccine?

Back 29

combination Ribivarin and pegylated interferon gamma.

only works in 30 to 40% of people.

also, liver transplant (leading cause of liver transplant in US).

NO HCV VACCINE.

Front 30

how do we do PEP for HepC?

Back 30

no antivirals -

no IG's.

Front 31

describe the hepatitis A virus: what interesting living characteristics?

what does kill it?

Back 31

It's non enveloped, icosahedral capsid,

ssRNA, positive strand.

its structure makes it STABLE TO ACID with pH below 1, solvents, detergents, salt.

it can live at 4 degrees for weeks, up to 56 degrees for awhile..

can kill with chlorine, formaline, uv radiation, peracetic acid, b-bpropiolactone.

Front 32

once invaded, what does the virus do?

Back 32

lives in the cytoplasm the entire time - it makes its own RNA dependent RNA polymerase.

Note that it binds to the HAVCR=1 receptor to get in.

Front 33

viral pathogenesis - time course of disease and how illness is caused?

Back 33

like usual, no direct cytopathology - it's immune driven killing of hepatocytes.

Also, as usual, peak infectivity is before onset of symptoms (2 weeks) - shed into stool.

Front 34

how is disease spread?

Back 34

fecal oral route (close personal contact, sex, child day care centers)

contaminated food/water

blood exposure (rare) - IVDU

Front 35

what is chronic HepA like?

Back 35

no chronic hep a exists.

Front 36

If HAV is expected, what tests can be run?

Back 36

look for Anti-HepA-IgM - this comes up first and goes away after infection.

In contrast, Anti HepA-IgG goes up and stays up for life - so it's a marker of previous infection. Can test for both.

also can be positive for this after HepA vaccine.

Front 37

treatment/prevention?

Back 37

there is a HepA vaccine, given only to at-risk populations. Two vaccines licensed, in fact. Works great.Travelers.

depend on hygiene/sanitation.

can also use Ig's Pre and Post exposure to prevent onset of illness.

Front 38

Hepatitis E - structure? how do you get it? diagnose? what does chronic disease look like?

Back 38

ssRNA, + stranded, as usual. Fecal Oral (like A). Mostly poop contaminated water, like in monsoons.


not a lot of person to person.

diagnose by history (travel), HepE IgM's.

no person to person.


no chronic disease.

Front 39

prevention and treatment of HepE?

Back 39

avoid drinking water and ice. uncooked shellfish/fruits/vegetables not peeled.

IG made from westerners isn't going to help, as they have no immunity.

Not known if foreigner IG helps.

Front 40

through WHAT does HEP B bud?

Back 40

the ER.