So let's start with
hepatitis C virus.
Transmitted via a parenteral
or blood exposure route,
but also exposure to other blood
and body fluids, via sexual contact
or perinatal exposure - a baby's
born to hepatitis C-infected mothers.
The clinical manifestations are,
or include acute infection, which overall,
is milder than
hepatitis B virus,
a chronic infection which
occurs in 3/4 of the cases.
The viremia associated with that
chronic infection lasts for at least,
in fact, frequently over 10
years, and occasionally
not as severely as hepatitis B
but occasionally is
associated with progression to
cirrhosis of the liver with liver
failure and a need for transplantation.
Antibodies acquired during any
stage of this don't give immunity,
and in fact, it has been difficult
to obtain and create, I should say,
a successful hepatitis C vaccine
because the envelope proteins
expressed by hepatitis C
are quite variable there's
changing, so it's a shifting target.
Looking at the table on the
right side of the slide,
is a bit of a closer drill
down to what acute hepatitis
looks like in the
setting of hepatitis C.
The prodromal phase is
very much a non-specific,
viral illness with fever,
malaise, and anorexia.
The preicteric, meaning prior to
onset of jaundice and liver failure,
is an escalation of gastrointestinal-
type symptoms, so nausea,
vomiting, nonspecific abdominal
pain, and then fever with rigors.
And then the icteric phase when
there is an acute hepatitis,
assuming that the patient hasn't bypassed
that and gone into the chronic phase.
But acutely, there will be rapid
onset of jaundice with dark urine,
increasing liver enzymes,
exactly as you would expect,
and even a mild hepatitis A case
where there's acute hepatitis.
The CDC recommends hepatitis
C screening for 2 populations.
First, all adults over the age of 18
should be tested once in their lifetime.
And second, all pregnant women during
each pregnancy should be tested once.
The exception to these
rules is in areas
where the prevalence of HCV
infections is below point 0.1%.
The universal screening is
performed in a stepwise approach.
The first test performed to look
for the presence of HCV antibodies.
This test means the patient's immune
system has either been exposed to the virus
at a previous point in time or
there's an active infection.
This test alone doesn't discriminate
between these two possibilities.
So if positive, a second test
is done looking for HCV RNA.
If there's positive
reaction in this test,
the patient is determined to
have an active viral infection.
The flowchart in this slide
represents the testing protocol
for working with a patient who is
suspected of having an HCV infection.
Notice that unlike in the
universal screening protocol,
testing for the HV antibodies,
as well as the HCV RNA
are done simultaneously,
rather than in a stepwise approach.
This change is made as a way to prevent
false negative results for patients
who may have been recently
exposed to the virus,
but not had enough time
to mount a sufficient
to form antibodies.
Here we can see a chart that
plots antibody levels over time.
This red box in the
lower left corner
illustrates the window I
mentioned on the previous slide.
This is effectively the lag and
time between a virus exposure
in the immune systems response to generate
antibodies to the detectable level.
As you can see, this immune system
response can take up to 2 months,
during which time a test looking only
for HCV antibodies would be negative.
During this window,
liver enzymes can begin to rise.
So a new hepatitis workup should
include both an HCV antibody test
as well as a simultaneous
test for HCV RNA.
If the HCV antibody
test is negative,
while the HCV RNA
test is positive,
that would indicate the patient
has an acute HCV infection.
Prevention and treatment.
Well, of course, the best treatment
is prevention, in the first place,
and so all blood or blood donors and
transplant for solid organ donors
are screened by ELISA,
which is a very sensitive way to
look for presence of hepatitis C.
For those patients who
become infected through
a parenteral or
or even those babies born to
a hepatitis C-infected mother.
Treatment for HCV is recommended
for nearly all patients
and typically consists
of various combinations
of four direct acting
Each of these medications interferes with
the specific HCV proliferation process.
With treatment patients can become
permanently cured of the disease,
with most experiencing a
normalization of AST levels
and cessation of histological
progression of the liver disease.
The medication therapy chosen
depends on a mered factors,
usually consisting of which of the
6 major HCV genotypes are present,
the viral load, prior treatments
and the presence of liver fibrosis.
Treatment results tend to be
more favorable in patients
with less fibrosis in comparison
with those with cirrhosis.
are very expensive,
but ultimately represent
a cost effective treatment
when compared to the medical
to the incomplete
treatment of this disease.
This slide depicts the typical
proliferation cycle of HCV,
which each of the 4
red boxes representing
the target of an
These include protease
inhibitors, NS5A inhibitors,
NNP inhibitors and NS5B
The combination of ledipasvir and
sofosbuvir, brand name Harvoni
is currently the antiviral regimen of
choice for the majority of patients
with chronic HCV infections
in the United States.