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[Osmosis sound logo]
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So hepatitis --meaning like this inflammation of the liver--
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most commonly comes about because of a virus.
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These viruses tend to target the
cells in the liver, right?
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And when they get in and infect these cells,
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they tend to cause them to present these weird and abnormal proteins via their MHC class 1 molecules.
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And at the same time, you’ve also got these immune cells infiltrating the liver
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and trying to
figure out what’s going on.
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And so the CD8-positive T-cells recognize these abnormal proteins
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as a sign that the cells are pretty much toast.
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And the hepatocytes then go through
cytotoxic killing by the T-cells and apoptosis.
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Hepatocytes undergoing apoptosis are sometimes
referred to as Councilman bodies,
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shown on histology here.
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And this typically takes place in the portal tracts and the lobules of the liver.
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This cytotoxic killing of the hepatocytes
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is the main mechanism behind inflammation of the liver
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and --eventually-- liver damage in viral
hepatitis.
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As someone’s hepatitis progresses,
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we’ll see a couple of classic symptoms related to your immune system mounting an attack:
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like fever, malaise, and nausea.
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Additionally though, patients might have hepatomegaly,
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where their liver is abnormally large from inflammation --which also might cause some pain, right?
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As more and more damage is done to the liver,
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the amount of transaminases in their blood will increase.
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This is because your liver has these
transaminase enzymes so it can do its job of breaking down various amino acids.
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Typically the serum amino transaminase --or the amount [found] in your blood-- is pretty low.
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But when your hepatocytes start getting damaged, they start leaking these into the blood,
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So a common sign is a greater amount of both alanine aminotransferase --or ALT--
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and aspartate aminotransferase --or
AST.
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Typically, even though both are elevated,
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ALT will be greater than AST in viral hepatitis
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and it'll also be the last liver enzyme to return to normal.
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Also, elevated levels of atypical lymphocytes are common to see with viral hepatitis
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--known as atypical lymphocytosis.
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The lymphocytes are usually huge --very large--
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due to stimulation from antigens,
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in our case the hepatitis virus antigens.
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Patients often also end up developing jaundice,
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with a mix of both conjugated bilirubin and unconjugated bilirubin.
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The conjugated bilirubin leaks out when bile ductules are damaged or destroyed --when the hepatocytes die--
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because those hepatocytes make up some of its lining.
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Also, since these hepatocytes are dying,
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you start to lose the ability to conjugate bilirubin and make it water-soluble;
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and so, you end up with unconjugated bilirubin, as well.
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So, since there’s both conjugated and unconjugated bilirubin in the blood,
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some of the water-soluble conjugated bilirubin gets filtered into the urine,
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giving it this darker color.
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Another common finding is increased urobilinogen in the urine.
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Urobilinogen is produced when bilirubin is reduced in the gut by intestinal microbes.
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Normally, most of
that's reabsorbed and transported back to the liver
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to be converted into bilirubin
or bile again.
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But if these liver cells aren’t working right,
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that urobilinogen is redirected
to the kidneys and excreted,
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so you end up with more urobilinogen in your urine.
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If symptoms continue, or the virus sticks around for more than 6 months,
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viral hepatitis goes from being "acute" to being "chronic"
hepatitis.
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At this point, inflammation mostly happens in the portal tract.
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And if the inflammation
and fibrosis keep happening,
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we consider that a pretty bad sign,
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since it might be progressing
to postnecrotic cirrhosis.
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Now, there are five known "flavors" of hepatitis virus that have slightly different and unique properties.
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Hepatitis A is transmitted through ingestion of contaminated food or water,
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in other words the fecal-oral route,
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and is known to be acquired by travelers.
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Hepatitis A virus --or HAV, for short--
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is almost always acute. And there is essentially no chronic HAV.
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If we’re talking serological markers,
an HAV-IgM antibody indicates an active infection;
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whereas an HAV-IgG antibody
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is a protective antibody that tells us that there’s been recovery from HAV
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or vaccination in the past.
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Hepatitis E virus is actually pretty similar to HAV,
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with the same route of transmission --oral-fecal.
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And it's most commonly acquired through undercooked seafood or contaminated water.
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It also doesn’t have much of a chronic state.
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And HEV-IgM antibodies tell us that there’s an active infection
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and HEV-IgG antibody is protective and signals recovery --just like HAV.
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Two big differences to note, though,
between these two guys
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is that one: only HAV has the option for immunization;
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and two: HEV infection for pregnant women can be very serious,
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And [it] can lead to acute liver failure, also sometimes called fulminant hepatitis.
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All right. Next on the docket is Hepatis C virus.
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Now this guy is transmitted via the blood.
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So it could be from childbirth, intravenous drug abuse,
or unprotected sex.
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HCV usually does move on to chronic hepatitis.
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And there are a couple of tests that we use to help diagnose HCV.
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One way is by enzyme immunoassay.
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In this case, we’d screen
for the HCV-IgG antibody.
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If present, it doesn’t necessarily confirm acute, chronic, or even resolved infection,
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because it isn’t regarded as a protective antibody --like it is in HAV and HEV.
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To get more specific confirmation, you might use recombinant immunoblot assay,
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which helps confirm HCV.
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It’s more specific, but less sensitive than the immunoassay.
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Clinically, recombinant immunoblot assay doesn’t provide much usefulness
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and actually needs an additional, supplemental test if it's positive.
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That being said, the gold standard
for HCV diagnosis is an HCV RNA test.
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Using PCR --or polymerase chain reaction-- this method
can detect the virus very early on
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--as early as one to two weeks after infection.
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Basically, it detects the levels of viral RNA in the blood,
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which tells us the levels of virus
circulating.
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If RNA levels begin to decrease, we know that the patient’s recovering;
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if RNA remains the same, the patient probably has chronic HCV.
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Okay. On to hepatitis B.
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HBV is just like HCV in that it’s contracted via the blood.
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So [it's through] the same routes --like childbirth,
unprotected sex, and others.
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HBV, however, only moves on to chronic hepatitis in twenty percent of cases overall.
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But it also depends on the age that someone gets infected.
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For example, children less than six years old are most likely to get chronic infections --about fifty percent.
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And that percentage increases the younger they are.
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Also, chronic HBV is known to be linked to liver cancer.
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And all these things make HBV and the serology of HBV
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a super-important concept
to understand.
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And kind of like hepatitis C, we can use a variety of testing methods --like PCR--
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to look for certain markers, especially the HBV antigens.
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And the presence --or absence-- of each of these, at different time points,
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can tell us different things.
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All right. So the key marker for HBV infection is the HBV surface antigen.
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And this is going to be like the super-villain in this story.
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And this evil-doer lives on the surface of the virus --here-- and we can call it HBsAg
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--meaning: Hepatitis B
surface antigen.
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Another marker, though, is a core antigen
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--meaning that these antigens
come from the core of the virus-- HBcAg.
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Think of these like the dispensable henchmen that
work inside the villain’s evil factory.
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Finally, there’s this other antigen --called the e-antigen-- which is secreted by infected cells;
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and so, it's this marker of active
infection.
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These are like the by-products of the factory.
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And along with viral DNA, they tell us that it’s replicating and infecting.
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All right. So at the onset of infection, during the acute phase,
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our surface antigen super-villain will definitely be present, and will come up positive.
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And its factory will be
pumpin’ out both viral DNA and e-antigen.
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At this point, the immune system produces IgM antibodies against the core antigens
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--against the henchmen-- so think of these like your basic police force that work against the core henchmen.
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These antibodies hack away at the core antigens and they really try their hardest.
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But in order to actually defeat this villain, this virus, you need to go for the supervillain, right?
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The surface antigen. So, we need a superhero
to go after it.
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So, in this story the IgG
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antibody for the surface antigen is our superhero.
At this point, the host enters this spooky
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phase called the window, where neither the
supervillain nor the superhero can be detected,
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because they’re both so low, and this can last
from several weeks to months, it’s like
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this war’s being waged but we don’t know
who’s coming out on top. The only thing
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you can detect during this stage is the IgM
core antibodies, the police force. At this
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point, two things can happen, if the superhero
comes out, the IgG antibodies to the surface
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antigen, then we’re golden, and this means the
day is saved and we win. The other possibility
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is that the supervillain wins, and surface
antigens are still, again, detected, there may
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also be a presence of HBV DNA and e-Antigen
because it’s now replicating and the factory's up and running again.
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The main point though is that there will not be
the IgG for surface antigens, our superhero.
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Regardless of who wins, the IgM antibodies,
the police force, will be promoted to IgG
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by about 6 months time, but this does not mean that
the host is protected. So it’s important
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to note that we need this surface IgG superhero
to win, but we can have core IgG and still
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lose. If the battle’s lost, the host transitions
into chronic viral hepatitis, defined by it
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continuing after 6 months. When chronic, the
host could present as, sort of healthy, and will
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likely have the presence of surface antigen,
core antibody, and no DNA or e-Antigen, basically
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saying that the supervillain’s there, it’s
just not replicating, and at this point the
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host is contagious, but there’s lower risk.
The other option is that they’re infective,
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meaning the whole villain force is active
along with an overwhelmed police force. This
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state increases the risk for postnecrotic
cirrhosis and hepatocellular carcinoma. One
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way to get around this whole fiasco is by
immunization, which skips these steps and
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gets you right to the IgG superhero antibody
for surface antigen. Alright, last but not
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least, well maybe it's the least, I dunno. Anyways,
Hepatitis D virus is unique in that it needs
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HBV, meaning that it can only infect the host if that host also has
HBV. If it infects at the same time, it’s
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called co-infection, if it infects sometime
later, it’s called superinfection, which
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is considered to be more severe that co-infection.
If either the IgM or IgG antibody are present,
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that indicates an active infection, so in
this case the IgG is not a protective antibody.
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And that is a very brief overview of viral hepatitis.
