Elastography in Diffuse Liver Disease - HD

Introduction

My name is Oli.
I'm from Italy.
I'm a researcher at the University of Pavia,
and the topic of a lecture today is elastography in
diffuse liver disease.
In chronic liver disease.

Prognosis and Management in Chronic Liver Disease

The prognosis and management depends largely on the extent
and progression of liver fibrosis.
This is particularly true in patients
with chronic hepatitis C in this case,
liver fibrosis is the most important predictor
of outcome and influence, dedication for
antiviral treatment.
Recent works suggests that the liver fibrosis
may be modified by treatment.

Liver Biopsy: Gold Standard and Limitations

Liver biopsy is the gold standard
for assessing liver fibrosis.
It has a low mortality
and a low, morbidity rate.
A recommended specimen should a length of
at least 15 millimeter
and a correct diagnosis when the, length
of the specimen is adequate dismissed.
One case out of four.
There are few histological scoring systems.
The most used one is the metaverse scoring system
is in a five point scale from zero.
That means no fibrosis.
F1 portal fibrosis without sep
F two cept, F three man without cirrhosis
and F four cirrhosis.
F two is a significant fibrosis.
F three advanced fibrosis.
Liver biopsy has several limitations,
is an invasive procedure.
It has a poor patient's compliance,
and there are risk of complications.
The diagnostic accuracy of the scoring systems is affected
by intra inter observer variability in the assessment
of fibrosis stage,
and it is not an ideal procedure for repeated assessment
of disease progressions.
Last but not the least, the costs
because of the limitations of liver biopsy as well
as development of new antiviral drugs.
The use of liver biopsy in the management of patients with
Hepatitis B and C has rapidly decreased
and the non-invasive methods have gained a,
popularity.

Introduction to Elastography

Elastography shows the elastic property of tissues
that whereas ultrasound shows the acoustic properties
of a tissue and these two are not related to each other.
Elastography is a vi puration
under stress.
Stiffer tissues shows a less longitudinal
displacement and an higher PL speed of,
displacement in the transverse plane.

Transient Elastography (FibroScan)

The first available technique has been trans cystography,
which is implemented in the fibrous scan device.
The first paper using a trans cystography in the assessment
of liver fibrosis has been published in,
2003.
The device has a probe with a tip at the end
by pressing a button.
The tip, eats the skin
and the sheer wave that originates
at the level of the skin propagates into the liver.
They propagates for,
about
four five centimeter
and is in this, volume of the liver
that the stiffness is assessed.
The velocity of the sheer wave are, is
directly related to the stiffness of the tissue.
This slide represent the propagation of the elastic wave.
With a different fibrosis stage, the propagation
of the velocity increases as a function
of fibrosis staging.
The reproducibility of the technique has been shown
excellent for both inter server
and the intra observer agreement
with in an intraclass correlation coefficient
of 0.98.
This coefficient goes from zero to one.
The agreement is reduced in patience with a lower degrees
of apathic fibrosis in case of hepatic ketosis.
And when there's an increased BMI in case
of a lower degree of hepatic fibrosis, it is understandable
that the agreement is reduced
because the fibrosis in the liver is not homogeneous.
This slide shows the values of a trans
cystography in normal subjects
and in subjects with the chronic viral
hepatitis differently from the, liver biopsy
and the fibrosis stage.
Here we have a continuous increase
of value starting from,
the value obtained in normal subject to liver cirrhosis.
When the stage of, cirrhosis is,
reached, there's an, increase of value
with time with worsening of liver cirrhosis.
Several studies, meta-analysis ever assess
that trans cystography is an accurate method in staging
liver fibrosis.
The semial works are that of cast
and zol published in 2005.
The performance of trans elastography has been assessed
in the first meta-analysis in 2008.
That take took into account 50 studies
and, 35 of these were abstract.
As you can see in these slides.
The mean area under the curve
for significant fibrosis, severe fibrosis
and cirrhosis was 0.84,
0.89 0.94.
Another meta meta-analysis has,
been published in 2011,
and in this meta-analysis, 40 studies were
included in these slides.
The, median cutoff values for F1, F two,
F three and F four are shown,
and also the sensitivity
and the specificity for each cutoff.
The, in this meta-analysis, the diagnostic accuracy
of the trans cystography did not significantly differ
between chronic hepatitis C
and chronic hepatitis B patients.
In any ME stage,
the liver stiffness cutoffs at a wider range
and were high
for a given fibrosis stage in chronic hepatitis B patients
With respect to chronic Hepatitis B patient,
the meta-analysis was possible for the following cutoffs
for F to stage seven kilo pascal F
three stage 9.5 kilo pascal, F four,
stage 12 kilo pascal, and here shown sensitivity
and specificity of the method.
We have performed a study to assess the performance
of liver stiffness in patients with, chronic hepatitis
using trans elastography.
And we have compared the results
obtained in our patients population without
of the meta-analysis we obtained similar,
values, but, the specificity of the,
our study was higher
in 2011, the European Association for the Study
of Liver Disease as endorse the use of a trans
cystography for assessment of liver fibrosis in patients
with chronic hepatitis C
before starting the treatment.

Limitations of Transient Elastography

The limitations of, trans cystography is
that the method is difficult
to use in OB patients,
but now there's the availability of a new probe,
the Excel probe that has been proposed for overweight
and OB patients with this probe,
the median liver stiffness values are lower.
The technique cannot be performed in patients with
atic ASEs.
This is because the sheer waves originates.
Were at level of the skin
and they cannot propagate into the words.
The failures have been observed in 4% of
examinations, and the unreliable results were obtained in
up to 17% of examinations.
Both were associated with obesity
and limited experience of the operator.
This is, a study that shows the discordance between,
fibrosis staging in fibrosis staging using the,
FibroScan Excel probe.
The median liver stiffness value are lower
with the Excel probe respect to the M probe, and,
but the diagnostic performance was similar
for both probes.

Ultrasound-Based Elastography

The other advantages of ultrasound elastography are
that liver stiffness measurements are guided
by the BMOD image.
The operator can search for an acoustic window in real time,
and the same ultrasound system use is used
for both ultrasound imaging and elastography.
In ultrasound elastography, the displacement of the shoe is
made by the force of the ultrasound beam.
There are two, possibility.
One is the point she wave elastography in point,
she wave elastography.
The shewas originate, level of the,
focus of the ultrasound beam.
Up
to now there are two ultrasound system
with the point she wave elastography technique.
One is the Philip system with the elastic PQ technique.
The other one is the Siemens system with the virtual
touch tissue quantification technique.
There are, nowadays,
also other company with the point share with
elastography, technique,
but the, there are no published papers
in the two dimensional she wave elastography technique
that is available on the explorer system.
It is possible
because of a very high frame rate to,
change in real time the focus of the ultrasound beam.
So it is possible to obtain, not only the value
of the, stiffness,
but also an image of the stiffness.
As you can see in this slide,
for all the techniques, the procedure is the same.
The measurements should be performed in fasting conditions.
The, patients is lying on the,
bed in dorsal decubitus with the right harm elevated
above the head for optimal intercostal access.
In the resting respiratory position, applying minimal
scanning pressure, with the probe,
the ROI should be placed at least
1.52 centimeter below the gly capsule
to avoid reverberation artifacts
and also, it should avoid
large liver vessels.

Point Shear Wave Elastography

I will shown now the results obtained
with a point she wave elastography.
The first available technique is the virtual touch tissue
quantification in the Siemens, system, the Cuson
s 2000 and S 3000.
The reproducibility of the technique is excellent
and it has been access in, several studies
goes from 0.84 to 0.87.
Several studies have been published and also meta-analysis.
I'll show you, this studies, publish
in 2011.
159 consecutive patients
with chronic hepatitis C were enrolled.
And on the same day
before performing liver biopsy, trans elastography
and she wave elastography were performed.
As you can see here, there was an increase
of the stiffness with the increase of the liver fibrosis,
both with the trans elastography
and with the sheer wave elastography.
As you can see from the, rock curves, the accuracy
of the, method was,
significantly higher respect to trans elastography for
the assessment of significant fibrosis,
advanced fibrosis, and, cirrhosis.
In a meta-analysis that include 13 studies,
more than 1000 patients with a chronic liver disease.
The method, showed a higher rate
of reliable measurements,
but a similar predictive value respected to trans
cystography for significant fibrosis.
And, cirrhosis.
The ELA PQ technique is a point she wave elastography on the
Philips system, the reproducibility of method
that been assessed by our group.
And as you can see,
the concordance correlation coefficient is very high.
The reproducibility is excellent.
In this other study, it has been shown that,
live stiffness desire in men respect to women.
This results have been obtained not only
with the point share with elastography,
but also with the trans elastography.
We have assessed the accuracy of the,
this point shared wave elastography method, for,
liver fibrosis in consecutive patients
with a chronic liver disease that were scheduled
for liver biopsy in the same day.
Trans cystography
and point shared wave elastography were performed just
before the liver biopsy.
As you can see in the slides, the majority
of patients were male
and the body mass index was within the normal range.
We compared the results obtained in patients
with not significant fibrosis with that obtained
in healthy volunteers.
And as you can see in these slides with both trans
elastography and point elastography, there was
a significant difference between, values.
Healthy volunteers show the significantly lower values,
and these are the results obtained in patients
with chronic Hepatitis C.
There is an increase of, value with, with
each fibrosis stage with both
cental cystography and point shared wave elastography.
And the, results of the IC curves show that
the two methods, cental, elastography,
and point shared wave elastography have the same accuracy
in assessing significant fibrosis, advanced fibrosis
and, cirrhosis.

Two-Dimensional Shear Wave Elastography

The two dimensional, sheer wave elastography,
which is available on the supersonic system,
offered, the possibility to, see,
the image of liver stiffness in real time
in the sample box.
As it happens with, color doppler,
we have assessed the reproducibility of real time share
in healthy volunteer.
The,
intra
and the inter observer agreement were excellent.
When we assessed the agreement
measurements performed in different days, the,
novice operator showed a,
lower performance respect to the, expert.
This means that the technique as it happens with,
real time, ultrasound
is dependent on the experience of the operator.
The accuracy of,
the two dimensional shared wave elastography has been
assessed by our group in patients with chronic hepatitis C.
They were consecutive patients
and on the same day, trans
elastography in the shared wave elastography
and liver biopsy soon afterward was well performed.
There was an increase of the, values
for each fibrosis stage, both with the she wave elastography
and the T trans center sheer
with elastography performed significantly better.
In the assessment of, significant fibrosis

Confounding Factors in Liver Stiffness Assessment

With the liver elastography, we assess the stiffness
of the liver that is directly related
to liver fibrosis, but it's a stiffness, not fibrosis.
Thus, the confounding factors should be taken into account.
The stiffness increases with exacerbation
of acute he hepatitis that is associated with the flares
of transaminases.
So the effect of nacro inflammation should be taken into
account and the results should always be evaluated
in clinical settings.
The stiffness of the liver increase in the case of
congestive heart failure, the feeding in
extra pathic cholestasis and in deep inspiration
because there's an increase of the
intraabdominal pressure.
So transiently stop breathing in a neutral position
is optimal for measurements.

Guidelines and Recommendations

There are guidelines for the assessment of,
liver fibrosis with the development
of the new drugs for the, treatment
of patients with chronic Hepatitis C,
the European Association for the Study of Liver Disease
as it should, the new guidelines for treatment of patients
with he hepatitis C in April, 2014 this year.
And, in this guidelines it is stated
that fibrosis stage can be assessed
by non-invasive method initially
with the liver biopsy reserved.
For cases where there's uncertainty
or potential additional etiologies
For follow up of untreated patients of patients
with treatment failure, it is recommended
to use non-invasive method for fibrosis staging,
also, the Canadian Association for the Study
of the Liver have endorsed the use of elastography
for assessment of liver fibrosis in patients
with chronic hepatitis C.
The NICE guidance recommends
to offer antiviral treatment without a liver biopsy
to adults with a trans CYSTOGRAPHY score
equal to or above 11 kilo pascal
to not offer liver biopsy to adults with a value
below six kilo pascal when the
transaminases are normal
and the viral load is low
to offer an annual reassessment
of liver disease using transient elastography to others
who are not taking antiviral treatment,
combining the results of a liver cystography
with other bio biomarker in this case,
the platelet count was used that could,
increase the accuracy of the method
in 2013, the European Association
or Ultrasound Medicine
and Biology as it should, the guidelines
and recommendation on the clinical use
of ultrasound elastography.
This guidelines are available for free on the FSO
website, the word federation for Ultrasounding Medicine
and Biology presented the ELASTOGRAPHY guidelines
in the meeting in Sao Paulo in Brazil,
and they are going to be published at the end
of, this year.

Conclusion

Thank you for your attention.