CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2008;6:1263–1269
Reproducibility of Liver Stiffness Measurement by Ultrasonographic
Elastometry
JÉRÔME BOURSIER,*,‡ ANSELME KONATÉ,*,‡ GABRIELLA GOREA,* STÉPHANE REAUD,‡ EMMANUEL QUEMENER,*
FRÉDÉRIC OBERTI,*,‡ ISABELLE HUBERT–FOUCHARD,*,‡ NINA DIB,*,‡ and PAUL CALÈS*,‡
*University of Angers, IFR 132, HIFIH Laboratory (UPRES 3859), Angers; and ‡University Hospital, Hepatogastroenterology Department, Angers, France
Background & Aims: Fibroscan is a noninvasive device
that assesses liver fibrosis by liver stiffness evaluation (LSE)
with ultrasonographic elastometry. We evaluated LSE re-
producibility and its influencing factors. Methods: LSE
was performed by 4 experienced physicians (>100 LSEs) in
46 patients with chronic liver disease at 4 different ana-
tomic sites. Additional LSEs were performed for ancillary
aims, so that 534 LSEs were available. Results: Overall
interobserver agreement for LSE results was considered as
excellent, with intraclass coefficient correlation (Ric) of
0.93. Low LSE level, nonrecommended sites, LSE interquar-
tile range >25%, and body mass index >25 independently
decreased agreement. Thus, agreement was fair (Ric ⴝ 0.53)
for LSE <9 kilopascals and excellent (Ric ⴝ 0.90) beyond.
The best measurement site for LSE reproducibility was the
median axillary line on the first intercostal space under the
liver dullness upper limit, with the patient lying in dorsal
decubitus. When LSE results were categorized into fibrosis
Metavir stages, interobserver discordance was noticed in
about 25% of the cases and was the highest for F2 and F3
stages and the lowest for F4. Intraobserver (Ric ⴝ 0.94),
intersite (Ric ⴝ 0.92– 0.98), and interequipment (Ric ⴝ 0.92)
agreements for LSE results were excellent. Preliminary stan-
dard ultrasonography or probe pressure changes did not
improve interobserver agreement. Conclusions: The best
measurement site for LSE is the one generally used for liver
biopsy. Reproducibility of LSE is globally excellent but is
fair in patient with low liver stiffness. The fibrosis diagno-
sis by ultrasonographic elastometry in low stages or cate-
gorized into fibrosis Metavir stages must be interpreted
with caution.
A ssessing the degree of liver fibrosis in chronic liver disease
is very useful for patient management. Noninvasive diag-
nosis of hepatic fibrosis gained considerable ground during the
past few years.1 The first developed tools were blood tests
combining several markers included in algorithms.2 APRI is the
easiest score to use,3 Fibrotest is the most validated algorithm,4
and FibroMeter seems the most accurate.5,6
More recently, a device allowing liver stiffness evaluation
(LSE) by ultrasonographic elastometry (FibroScan; EchoSens,
Paris, France) was developed.7 FibroScan is becoming increas-
ingly popular because several recent studies have shown that
liver stiffness is well-correlated with fibrosis Metavir stages8; in
addition, it is an easy, rapid, noninvasive, and painless exami-
nation. However, there are few data about characteristics of LSE
reproducibility.9 The main aim of this prospective study was to
evaluate the reproducibility of liver stiffness measurement by
transient elastography with Fibroscan. The secondary aims were
to evaluate the following influencing factors: observer, device,
liver stiffness value, anatomic conditions, body mass index
(BMI), knowledge of previous measurement, location by stan-
dard ultrasonography, and probe pressure.
Patients and Methods
Patients
All patients included in the study were hospitalized in
the Department of Hepato-Gastroenterology of the Angers Uni-
versity Hospital, France, for a clinical assessment of chronic
liver disease. The only noninclusion criterion was ascites, which
makes LSE impossible.7 The study protocol conformed to the
Helsinki Declaration and was approved by the local Ethics
Committee. All patients gave their informed consent before
being included.
Observers
Four physicians specialized in hepatology performed
the examinations, and each had already performed at least 100
LSEs before the study: judge A, 750; judge B, 109; judge C, 227;
and judge D, 117 LSEs. In a reproducibility study, each patient
should classically be examined by all the observers to guarantee
the highest homogeneity. However, this design was not possible
here because the duration of all LSEs performed by one judge
was approximately 30 – 45 minutes.
Therefore, each patient was only examined by 2 judges. This
needed 2 different judge pairs who consequently examined 2
different patient groups (Table 1); judges A and B examined a
group of 22 patients (P1), and judges C and D examined a
group of 24 patients (P2). Each patient was first examined by
the most experienced judge (A for P1, C for P2) and second by
the less experienced judge (B for P1, D for P2). Thus, overall
interobserver agreement was evaluated by comparing the LSE
results between the first (O1: A or C) and second (O2: B or D)
observers in the 46 patients included in the study. Naturally,
the judge pair (P1 or P2) was statistically controlled as a po-
tential bias.
Abbreviations used in this paper: APRI, ASAT-to-Platelets-Ratio-Index;
BMI, body mass index; c⌬LSE, crude difference between observer LSE
results; IQR, interquartile range; ␬w, weighted kappa index; kPa, kilo-
pascal; LSE, liver stiffness evaluation; Ric, intraclass correlation coef-
ficient; r⌬LSE, relative difference between observer LSE results.
© 2008 by the AGA Institute
1542-3565/08/$34.00
doi:10.1016/j.cgh.2008.07.006
1264 BOURSIER ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 6, No. 11

Table 1. Study Design: Assignment of Judges According to
Patient and Observer Groups
Observer group
Patient
group Patients (n) First observer (O1) Second observer (O2)
P1 22 Judge A Judge B
P2 24 Judge C Judge D
NOTE. Interobserver agreement was evaluated between O1 and O2.
Liver Stiffness Evaluation
Examination conditions. Examination conditions
were those recommended by Echosens.7 The second observer
was blinded to the previous results of the first observer.
Definitions. An LSE corresponded to all the measure-
ments recorded during an examination. The LSE success rate
(%) was calculated as the ratio of number of valid measure-
ments/total number of measurements. The LSE result was
expressed in kilopascals (kPa) and corresponded to the median
of all the valid measurements performed within the examina-
tion. Metavir fibrosis stages were determined from the LSE
result by applying liver stiffness cutoffs previously published by
Foucher et al10 that were calculated in various causes of chronic
liver disease as in our study. Interquartile range (IQR) is an
index of intrinsic variability of LSE corresponding to the inter-
val around the LSE result containing 50% of the valid measure-
ments between the 25th and 75th percentiles. LSE IQR (kPa)
was expressed when necessary as LSE IQR ratio (%): LSE IQR/
LSE result. When 10 valid measurements were obtained, LSE
was stopped, and the result was considered as reliable. However,
a LSE could not exceed a total of 20 (valid and invalid) mea-
surements. In a previous study, accuracy of LSE for the diag-
nosis of significant fibrosis or cirrhosis was similar whether 3, 5,
or 10 valid measurements were recorded.11 Thus, as in previous
studies,10,12 we defined an LSE result as acceptable when the
LSE success rate was at least 30%, corresponding to 6 valid
measurements according to our protocol.
apply a higher probe pressure on the skin and to perform
another 15 measurements. High pressure was defined as a grade
9 –12 on the 12-grade scale of recommended pressure. This
procedure was performed only on the first site for which diffi-
cult LSE was observed.
Fibrosis Blood Tests
To determine which observers provided the reference
LSE results, we evaluated the correlation between O1 or O2 LSE
results and fibrosis blood tests taken as an independent fibrosis
reference: APRI3 and FibroMeter.5
Statistics
Agreement was estimated with the intraclass correlation
coefficient (Ric) for quantitative variables, kappa index for bi-
nary variables, and weighted kappa index (␬w) for ordinal vari-
ables. Ric combines correlation and similarity but does not take
into account chance-expected agreement unlike ␬.14 Its mean-
ing is Ric ⱖ0.87, excellent; 0.87 ⬎Ric ⱖ0.71, good; 0.71 ⬎Ric
ⱖ0.50, fair; and Ric ⬍0.5, poor agreement.15
We analysed the independent agreement predictors in the set
of 368 LSEs performed by observers O1 and O2 in sites I–IV
(Table 2). The statistical comparison of agreement required us
to use observer discrepancy. Discrepancy was expressed in 2
ways, either crude difference (c⌬LSE expressed in kPa): absolute
value of (O2 LSE result – O1 LSE result) or relative difference
(r⌬LSE expressed in %): absolute value of [(O1 LSE result – O2
LSE result)/O2 LSE result]. Statistical software used was SPSS
for Windows, version 11.5.1 (SPSS Inc, Chicago, IL).
Results
Patients
Forty-six patients were enrolled in the study, 22 in the
patient group P1 and 24 in the group P2 (Table 1). Their
characteristics at inclusion are summarized in Table 3. Globally,
534 LSEs were performed during the study (Table 2); 184 LSEs
were performed on sites I–IV by each observer O1 and O2 (46

Liver Stiffness Evaluation Influencing Factors

Measurement site (LSE #1–#4). All judges had to
perform an LSE on 4 different sites (Figure 1; Table 2). Site IV
corresponded to the usual site for percutaneous liver biopsy.13
Screen withdrawal (LSE #5). Judges A and D per-
formed a fifth LSE on site IV, with LSE results not shown on the
Fibroscan screen.
Location by standard ultrasonography (LSE #6).
Judges A and D performed a sixth LSE on the best site located
by standard ultrasonography, defined by a minimum liver pa-
renchyma thickness of 6 cm without large vessel.7
LSE repeatability (LSE #7). Judges A and D per-
formed a seventh LSE in 20 patients. This LSE required 20 valid
measurements and was performed on the best LSE site accord-
ing to the observer’s opinion.
Interequipment reproducibility (LSE #8, #9). Judge
A had to perform 2 additional LSEs on a single measurement
site of his/her choice, each one with a different Fibroscan
device. This evaluation was realized in 17 patients, and results
of the first LSE were not communicated to the judge. Figure 1. Location of the liver stiffness measurement sites. LSEs were
Probe pressure. In case of difficult LSE (defined performed on the first or the second intercostal space under the upper
as ⬍10 valid measurements after 15 attempts), the judge had to limit of the liver dullness.
November 2008 REPRODUCIBILITY OF LIVER STIFFNESS MEASUREMENT 1265

Table 2. Types of LSEs Performed During the Study

Examination conditions
LSE # Judges LSE (n)a Site Decubitus Axillary line Intercostal spaceb

1 All 92 I Lateral Median First

2 All 92 II Dorsal Anterior First
3 All 92 III Dorsal Median Second
4 All 92 IV Dorsal Median First
5 A, D 46 IV Screen withdrawal
6 A, D 46 V Best site located by preliminary standard ultrasonography
7 A, D 40 VI 20 valid measurements on the best site (observer opinion)
8, 9 A 34 VII 2 LSEs on the same site, each one with a different Fibroscan
device
aTotal: 534.
bUnder the upper limit of the liver dullness.

patients ⫻ 4 sites, Table 2): LSE results varied from 1.5–75 kPa
(median, 11.9), and LSEs were acceptable for both O1 and O2
in 73.4% of the cases. O2 LSE result was considered as the
reference LSE result because it was independently associated
with the fibrosis blood tests (data not shown).
Liver Stiffness Evaluation Agreement
The material is the 184 LSEs performed by O1 and O2
observers on sites I–IV. Overall interobserver agreement was
considered as excellent with Ric of 0.93 (Table 4; Figure 2). After
conversion of LSE result into Metavir fibrosis stage,10 O1/O2
agreement was excellent (␬w, 0.80), and fibrosis stages were
concordant in around 75% of cases. O1/O2 discordance rate for
Metavir fibrosis stages was high in F2 and F3, moderate in F0/1,
and low in F4 (Figure 3).
Influencing Factors
Liver stiffness evaluation result. Interobserver
agreement for LSE results increased linearly as a function of
liver stiffness (Figure 4). Interobserver agreement was fair in
reference LSE results ⬍9 kPa with Ric of 0.53 and excellent
when ⱖ9 kPa with Ric of 0.90.
Liver stiffness evaluation interquartile range. In-
terobserver agreement for LSE result was excellent when LSE
IQR ratio was ⱕ25% and decreased in LSE IQR ratio ⬎25%
(Figure 5).
Body mass index. Interobserver agreement for LSE
result was excellent when the BMI was ⬍25 and decreased in
BMI ⱖ25 (Figure 6).
Liver stiffness evaluation site. Interobserver agree-
ment for LSE results was excellent in each site, but it was the
highest in site IV and the lowest in site I (Table 5). LSE
agreement was excellent between all sites (Table 5). LSE agree-
ment was excellent between sites IV and II or III (Table 6),
suggesting no influence of axillary line and intercostal space
tested. LSE agreement between sites I and IV was lower than the
previous ones, supporting again a lower reproducibility in lat-
eral than in dorsal decubitus.
Screen withdrawal, additional ultrasonography. LSE
agreements between LSE #4 and #5 or #6 were excellent (Ric ⫽
0.99), suggesting no influence of knowledge of previous mea-
surement on LSE result and no interest of location by standard
ultrasonography, respectively.
Liver stiffness evaluation repeatability. Agree-
ment between LSE results of the 10 first and the 10 last valid
measurements of LSE #7 was excellent (Ric ⫽ 0.94), suggesting
an excellent repeatability and intraobserver agreement of LSE.

Table 3. Patient Characteristics at Inclusion as a Function of Patient Group

Patient group
Both P1 P2 P valuea

No. of patients 46 22 24 —
Age (y) 34,45-50-62,83 34,44-50-61,74 34,45-51-64,83 .91
Male sex (%) 70 59 79 .14
BMI (kg/m2) 16.9,21.5-23.8-26.4,34.6 17.0,20.8-22.5-25.1,34.6 16.9,23.1-24.9-28.5,33.5 .05
Cause (%) .13
Alcohol 52 59 46
Virus 26 32 21
Others 22 9 33
AST (IU/L) 12,29-44-62,271 12,28-47-82,271 22,32-44-53,125 .67
Bilirubin (␮mol/L) 3,8-11-26,329 3,8-10-43,329 4,7-11-18,136 .70
FibroMeter 0.0,0.15-0.46-0.99,1.0 0.06,0.28-0.46-0.99,1.0 0.0,0.11-0.41-0.99,1.0 .52
APRI score 0.15,0.32-0.54-1.15,3.28 0.15,0.32-0.61-1.43,3.28 0.16,0.31-0.49-1.07,2.50 .46

NOTE. Quantitative variables are expressed as median (in bold), interquartiles, and extremes (in italic).
aMann-Whitney test or Fisher test between the patient groups.
1266 BOURSIER ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 6, No. 11

Table 4. LSE Results and Interobserver Agreement as a

Function of Patient Group
LSE (kPa)a
O1 O2 P valueb Ric

Patient groupc
Both 23.5 ⫾ 23.6 23.1 ⫾ 23.0 .64 .93
P1 33.6 ⫾ 26.5 34.2 ⫾ 26.4 .60 .93
P2 13.5 ⫾ 14.5 12.2 ⫾ 11.2 .12 .84
P valued ⬍.001 ⬍.001 — —
aO1: judges A (for P1) and C (P2); O2: judges B (P1) and D (P2).
bPaired comparison between O1 and O2 by Wilcoxon test (P1 and P2)
or t test (all).
cPatient groups: P1: judges A (O1) and B (O2); P2: judges C (O1) and

D (O2).
dUnpaired comparison between P1 and P2 by t test.
Interequipment reproducibility. LSE agreement be-
tween the 2 Fibroscan devices was excellent (Ric ⫽ 0.92).
Probe pressure. Difficult LSEs were noted in 43 of
the 368 LSE performed on sites I–IV (11.7%), mainly on site I
(86%). A high probe pressure did not significantly increase LSE
success rate (P ⫽ .43) and did not alter LSE result (Ric ⫽ 0.96).
Judge pair. Overall interobserver agreement was ex-
cellent in patient group P1 and good in P2 (Table 4). However,
LSE results were significantly lower in P2 than in P1 patients
(Table 4), precluding a reliable comparison of reproducibility
between both judge pairs. Therefore, this confusing factor,
judge pair, was evaluated. On one hand, O1 LSE result (P ⬍
.001), as expected, and judge pair (P ⫽ .002) were independent
predictors of O2 LSE result. On the other hand, O2 LSE result
was the only independent predictor of O1 LSE result (P ⬍ .001),
with no independent role for judge pair (P ⫽ .51).
Figure 3. Discordance rate for Metavir fibrosis stage between observ-
ers O1 and O2 as a function of anatomic site and reference (O2) Metavir
fibrosis stage. Discordance was defined by a difference of at least 1
fibrosis stage between O1 and O2 results.
Acceptable liver stiffness evaluation. The rate of
acceptable LSE was significantly different between observers O1
and O2, 87.5% and 79.9%, respectively (P ⫽ .03). However, this
difference did not influence interobserver reproducibility be-
cause all the previous results were similar whether the statistical
analysis was restricted to acceptable LSE in both O1 and O2
observers (detailed data not shown).
Observer Discrepancy
Crude discrepancy. c⌬LSE was independently asso-
ciated with O2 LSE IQR at the first step (P ⬍ .001), O2 LSE
result at the second step (P ⫽ .002), BMI at the third step (P ⫽
.006), and LSE site at the fourth step (P ⫽ .01). c⌬LSE grew
almost linearly as a function of O2 LSE result (Figure 7).
Finally, c⌬LSE was significantly different between the 4 LSE
sites and the smallest in site IV (Table 5).
Relative discrepancy. r⌬LSE was independently as-
sociated only with O2 LSE result (P ⫽ .02). r⌬LSE, plotted
against O2 LSE result, initially decreased and then reached a
plateau around 20%–30% by 5 kPa (Figure 7). In addition,
r⌬LSE was significantly different between the 4 LSE sites (the
smallest for site IV; Table 5).

Figure 2. Correlation of LSE results between observers O1 and O2, Figure 4. Interobserver agreement for LSE results as a function of
providing an agreement of Ric of 0.93. different intervals of LSE result (reference: O2) and anatomic sites.
November 2008 REPRODUCIBILITY OF LIVER STIFFNESS MEASUREMENT 1267

of fibrosis stages in the population studied, as recently demon-

Figure 5. Interobserver agreement for LSE results as a function of LSE
IQR ratio (reference: O2).
Agreement on Best Site
As already noted, interobserver agreement was the high-
est in site IV (Table 5). Interobserver agreement (Ric) for LSE
results also increased as a function of liver stiffness in site IV,
but it was always higher than that of other sites (Figure 4). LSE
IQR ratio, BMI, and judge pair had no influence on agreement
in site IV (Figures 5, 6, and Table 5, respectively). All these
results were similar when only acceptable LSEs in both O1 and
O2 observers were included in the statistical analysis.
Discussion
A recent study has already shown that interobserver
LSE agreement was excellent and was influenced by the BMI
and especially by the liver fibrosis level.16 However, these 2
factors were considered only as binary variables in this work
(Metavir Fⱖ2 and BMI ⱖ25), thus providing little information
for clinical practice. By evaluating the influence of several fac-
tors on LSE reproducibility, our study determined the precise
conditions required to obtain a reproducible LSE result.
Interobserver Agreement
Our study confirmed the excellent overall interobserver
LSE agreement reported recently by Fraquelli et al16 (Ric ⫽
0.98), with, however, a slightly lower result, Ric ⫽ 0.93. In fact,
Fraquelli et al limited their results to a per protocol analysis by
using a restrictive and arbitrary definition of acceptable LSE
with a success rate ⱖ60% and an IQR ⱕ30%. This was not an
“intention to diagnose” analysis according to the STARD rec-
ommendations.17 In addition, whereas Fraquelli et al used only
1 fixed site for each observer, in our study agreement was
evaluated in 4 sites with slightly variable LSE reproducibility.
strated for fibrosis blood tests.18
The increase in crude difference c⌬LSE as a function of LSE
result could suggest a lower interobserver agreement for high
LSE results (Figure 7). However, interobserver agreement was
better in high LSE results (Figure 4). Interobserver agreement is
thus better reflected by the relative difference r⌬LSE, which was
high (⫾60%) in low LSE results and thereafter rapidly decreased
to stabilize around ⫾20%–30% in LSE ⱖ5 kPa (Figure 7). This
30% variation of LSE could have a high implication in clinical
practice, especially for medium LSE. For example, a ⫾30%
interval around a stiffness measured at 10 kPa (ie, equivalent
Metavir F2–3 stages) would result in LSE result from 7–13 kPa,
ie, from F0 –1 to F4 in equivalent Metavir stages.9 With that
respect, after conversion of liver stiffness in Metavir fibrosis
stages according to Foucher cutoffs,10 our results showed a
higher discordance rate between the 2 observers for F2 and F3
stages (Figure 3). Therefore, diagnosis of noncirrhotic fibrosis
stages by LSE must be carefully interpreted.
Influence of Anatomic Site
Site IV was the most suitable site according to LSE
reproducibility: (1) interobserver agreement (Ric) was the high-
est in site IV; (2) crude and relative differences between the 2
observers’ LSE results were significantly the smallest at site IV;
(3) the influence of liver stiffness level, LSE IQR, BMI, and judge
pair at site IV was much weaker on interobserver agreement
than that observed in all sites (Figures 4, 5, and 6; Table 5).
Thus, our study demonstrated that the best measurement site,
considering LSE reproducibility, is the median axillary line on
the first intercostal space under the upper limit of the liver
dullness with the patient lying in the dorsal decubitus position,
which corresponds to the site recommended by the FibroScan
manufacturer and to the one usually used for liver biopsy.
Figure 4 shows that agreement for LSE result was the best for
high LSE values recorded on the best measurement site. Thus,
on an individual basis, our results suggest that LSE is more
devoted to the diagnosis of cirrhosis. In this setting, a recent
meta-analysis has shown that LSE was more accurate to diag-
nose cirrhosis than significant fibrosis.8

Influence of Liver Stiffness Level

Fraquelli et al16 showed that interobserver agreement
was higher in Metavir Fⱖ2 fibrosis stages compared with Fⱕ1
stages. Our study confirmed this result; agreement increased
with the level of liver stiffness and was fair for liver stiffness
under 9 kPa. In addition, LSE result was the only factor inde-
pendently associated with the relative difference between the 2
observers’ LSE results and was identified as the second inde-
pendent predictor of the crude difference. Thus, overall inter- Figure 6. Interobserver agreement for LSE results as a function of
observer agreement for LSE depends on the relative prevalence BMI.
1268 BOURSIER ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 6, No. 11

Table 5. Influence of Measurement Site on Interobserver Agreement as a Function of Patient Group (Ric) and of
Interobserver Difference
Measurement site
I II III IV All

Patient group
P1 0.82 0.96 0.93 0.98 0.93
P2 0.75 0.85 0.80 0.97 0.84
Both 0.86 0.95 0.91 0.98 0.93
Interobserver difference
c⌬LSEa (kPa) 7.6 ⫾ 10.4 4.4 ⫾ 6.2 5.6 ⫾ 8.0 2.5 ⫾ 3.4 4.9 ⫾ 7.4b
r⌬LSEc (%) 34 ⫾ 39 25 ⫾ 21 41 ⫾ 59 19 ⫾ 18 30 ⫾ 39b
aCrude difference between O1 and O2 LSE results.
bP ⫽ .03 (paired Friedman test between the 4 sites).
cRelative difference between O1 and O2 LSE results.

Influence of Judge Expertise Other Influencing Factors

Interobserver LSE agreement was higher in patient Crude difference of LSE between observers provided
group P1 than in P2 (Table 4). This could be partially explained more independent factors than relative difference, and they
by the higher mean LSE result in P1 than in P2. Besides, judge were clinically plausible. Thus, the former is a finer descriptor of
pair has an independent influence only on LSE result in O2 influencing factors than the latter. Reference LSE IQR and BMI
observers but not in O1 observers. Taken together, those results were independent predictors. The role of BMI has already been
indicate a source of variability in P2 and O2, ie, in judge D. suggested.16 Our results showed that an LSE IQR ratio ⱕ25% is
Thus, the low expertise effect was more sensitive in this judge as required to consider a LSE result as reliable whatever the site.
a result of the lower mean level of LSE results. They even suggested that an LSE IQR ratio ⱕ10% produces a
very reliable result at the best site as a result of an optimal
Conversion of Liver Stiffness Evaluation interobserver agreement (Ric of 0.999).
Result Into Metavir Fibrosis Stage
On the best measurement site IV, interobserver LSE Conclusion
agreement was excellent. After converting LSE results into
Overall interobserver agreement for liver stiffness result
Metavir fibrosis stages, interobserver agreement was still excel-
assessed by ultrasonographic elastometry is globally excellent,
lent. However, calculated fibrosis stages were still discordant in
but agreement depends on several factors, especially stiffness
around 15% of the cases (data not shown).
level, because agreement is fair for LSE results ⬍9 kPa, whatever
This discordance rate raises the difficulty of the interpreta-
the anatomic site. Other factors decreasing agreement are a
tion of the LSE result. Actually, we do not know how to use the
high LSE range (IQR), high BMI, and anatomic site. The best
LSE result in clinical practice; therefore, LSE results are some-
site is that generally used for liver biospy. LSE IQR ratio ⱕ25%,
times converted into Metavir fibrosis stage according to pub-
especially ⱕ10%, produces reproducible LSE in the best site.
lished cutoffs.9 Nevertheless, these cutoffs are heterogeneous
Converting LSE result into fibrosis Metavir stage decreases
among the studies, and besides cause of chronic liver disease19
interobserver agreement, especially in F2 and F3 stages, and
and fibrosis stage prevalence, observer variability might partic-
thus should only be used cautiously as an ancillary descriptor of
ipate in such heterogeneity. In addition, the use of 3 cutoffs for
liver fibrosis by ultrasonographic elastometry.
3 diagnostic targets (ⱖF2, ⱖF3, F4) cumulates 3 misclassifica-
tion rates. Thus it seems necessary to privilege the use of
unconverted LSE result, but this requires determining its direct
clinical value. In this respect, recent studies have evaluated the
relationship between LSE result and portal hypertension: portal
pressure20 –23 and large esophageal varices.10,24

Table 6. Intersite Agreement (Ric) for LSE Result Between

Anatomic Site IV and Other Sites, With the
Ensuing Anatomic Condition Tested
Site
I II III

Site IV vs other 0.92 0.98 0.97

site (Ric)
Anatomic factor Lateral decubitus Axillary line Intercostal space
tested Figure 7. Relationship of the crude or relative difference between the 2
observers’ LSE results with the LSE result (in reference O2).
November 2008
References
1. Rockey DC, Bissell DM. Noninvasive measures of liver fibrosis.
Hepatology 2006;43:S113–S120.
2. Afdhal NH, Nunes D. Evaluation of liver fibrosis: a concise review.
Am J Gastroenterol 2004;99:1160 –1174.
3. Wai CT, Greenson JK, Fontana RJ, et al. A simple noninvasive
index can predict both significant fibrosis and cirrhosis in patients
with chronic hepatitis C. Hepatology 2003;38:518 –526.
4. Poynard T, Morra R, Halfon P, et al. Meta-analyses of FibroTest
diagnostic value in chronic liver disease. BMC Gastroenterol
2007;7:40.
5. Cales P, Oberti F, Michalak S, et al. A novel panel of blood
markers to assess the degree of liver fibrosis. Hepatology 2005;
42:1373–1381.
6. Cales P, De Ledinghen V, Halfon P, et al. Evaluating accuracy and
increasing the reliable diagnosis rate of blood tests for liver
fibrosis in chronic hepatitis C. Liver Int (Epub ahead of press).
7. Sandrin L, Fourquet B, Hasquenoph JM, et al. Transient elastog-
raphy: a new noninvasive method for assessment of hepatic
fibrosis. Ultrasound Med Biol 2003;29:1705–1713.
8. Friedrich-Rust M, Ong MF, Martens S, et al. Performance of
transient elastography for the staging of liver fibrosis: a meta-
analysis. Gastroenterology 2008;134:960 –974.
9. Castera L, Forns X, Alberti A. Non-invasive evaluation of liver
fibrosis using transient elastography. J Hepatol 2008;48:835–
847.
10. Foucher J, Chanteloup E, Vergniol J, et al. Diagnosis of cirrhosis
by transient elastography (FibroScan): a prospective study. Gut
2006;55:403– 408.
11. Kettaneh A, Marcellin P, Douvin C, et al. Features associated with
success rate and performance of fibroscan measurements for
the diagnosis of cirrhosis in HCV patients: a prospective study of
935 patients. J Hepatol 2007;46:628 – 634.
12. de Ledinghen V, Douvin C, Kettaneh A, et al. Diagnosis of hepatic
fibrosis and cirrhosis by transient elastography in HIV/hepatitis C
virus-coinfected patients. J Acquir Immune Defic Syndr 2006;41:
175–179.
13. Nousbaum JB. The role of liver biopsy in the management of
chronic hepatitis C. Gastroenterol Clin Biol 2002;26(Suppl 2):
B168 –179.
14. Winkfield B, Aube C, Burtin P, et al. Inter-observer and intra-
REPRODUCIBILITY OF LIVER STIFFNESS MEASUREMENT 1269
observer variability in hepatology. Eur J Gastroenterol Hepatol
2003;15:959 –966.
15. Rousselet MC, Michalak S, Dupre F, et al. Sources of variability
in histological scoring of chronic viral hepatitis. Hepatology
2005;41:257–264.
16. Fraquelli M, Rigamonti C, Casazza G, et al. Reproducibility of
transient elastography in the evaluation of liver fibrosis in pa-
tients with chronic liver disease. Gut 2007;56:968 –973.
17. Bossuyt PM, Reitsma JB, Bruns DE, et al. The STARD statement
for reporting studies of diagnostic accuracy: explanation and
elaboration. Clin Chem 2003;49:7–18.
18. Poynard T, Halfon P, Castera L, et al. Standardization of ROC
curve areas for diagnostic evaluation of liver fibrosis markers
based on prevalences of fibrosis stages. Clin Chem 2007;53:
1615–1622.
19. Beaugrand M. Fibroscan: instructions for use. Gastroenterol Clin
Biol 2006;30:513–514.
20. Bureau C, Metivier S, Peron JM, et al. Transient elastography
accurately predicts presence of significant portal hypertension in
patients with chronic liver disease. Aliment Pharmacol Ther
2008;27:1261–1268.
21. Carrion JA, Navasa M, Bosch J, et al. Transient elastography for
diagnosis of advanced fibrosis and portal hypertension in pa-
tients with hepatitis C recurrence after liver transplantation. Liver
Transpl 2006;12:1791–1798.
22. Lemoine M, Katsahian S, Nahon P, et al. Liver stiffness mea-
surement is correlated with hepatic venous pressure gradient in
patients with uncomplicated alcoholic and/or HCV related cirrho-
sis. Hepatology 2006;44:204A.
23. Vizzutti F, Arena U, Romanelli RG, et al. Liver stiffness measure-
ment predicts severe portal hypertension in patients with HCV-
related cirrhosis. Hepatology 2007;45:1290 –1297.
24. Kazemi F, Kettaneh A, N’Kontchou G, et al. Liver stiffness mea-
surement selects patients with cirrhosis at risk of bearing large
oesophageal varices. J Hepatol 2006;45:230 –235.
Address requests for reprints to: Paul Calès, MD, Service d’Hépato-
Gastroentérologie, Centre Hospitalier Universitaire, 49933 Angers Cedex
09, France. e-mail: paul.cales@univ-angers.fr; fax: 33-2-41-35-41-19.
We thank Dermot O’Toole for manuscript review.
Supported by the following Grant: PHRC 2006 from the French
Department of Health.