Castera_edit_Layout 1 28/09/2009 10:21 Page 46
Liver
curves (AUROCs) ranging from 0.79 to 0.83 for the diagnosis of Santé (HAS) for the first-line assessment of liver fibrosis in patients
significant fibrosis and from 0.95 to 0.97 for cirrhosis. In a recent with hepatitis C without co-morbidities.
53
meta-analysis,
47
the mean AUROCs for the diagnosis of significant
fibrosis and cirrhosis were 0.84 (95% confidence interval [CI] Monitoring of Disease Progression
0.82–0.86) and 0.94 (95% CI 0.93–0.95), respectively. Cut-off values Another promising and attractive application of non-invasive
with optimal diagnostic accuracy were defined for each stage of markers and TE is in the monitoring of liver fibrosis progression. In
fibrosis. In patients with CHC, a cut-off value of 12.5kPa
44
cirrhotic patients with CHC, liver stiffness values range from 12.5 to
yielded positive and negative predictive values of 77 and 95%, 75kPa. It is obviously of great interest to understand whether cut-
respectively, for the diagnosis of cirrhosis, whereas a cut-off value offs of clinical value exist across this wide range of measurements.
of 14.6kPa
43
yielded positive and negative predictive values of 78 Preliminary results from our group
54
suggest that liver stiffness
and 97%, respectively. values in cirrhotic patients may increase as liver disease is more
advanced. In this retrospective study, the cut-off values of 27.5,
However, liver stiffness measurements can be difficult in obese 37.5, 49.1, 53.7 and 62.7kPa had >90% negative predictive value for
patients or those with a narrow intercostal space and impossible the presence of oesophageal varices (OVs) stage 2/3, Child-Pugh
in patients with ascites. In our experience in more than 2,000 scores B or C, past history of ascites, hepatocellular carcinoma and
examinations, liver stiffness could not be measured in 4.5% of cases oesophageal bleeding, respectively. In line with these findings, a
and was associated in multivariate analysis with obesity (body mass correlation between liver stiffness values and portal hypertension
index [BMI] >28).
48
TE results may also be influenced by acute liver assessed either by the presence of OVs on upper gastrointestinal
injury (as reflected by ALT flares), with the risk of overestimating endoscopy
55–58
or the measurement of hepatic venous pressure
liver stiffness values.
45,49,50
gradient (the gold standard for the diagnosis and staging of portal
hypertension)
56,57,59,60
has recently been reported.
The new alternative imaging techniques available include magnetic
resonance (MR) elastography, which can be implemented readily on However, in clinical practice the diagnostic performance of TE and
standard MR imaging (MRI) systems with additional hardware, serum markers
55–58
remains insufficient (no more than 70% of
diffusion-weighted MRI, which measures the apparent diffusion patients being correctly classified) for them to be able to replace
co-efficient of water (a parameter that is dependent on the tissue upper gastrointestinal endoscopy for the screening of OVs. Long-
structure), optical digital analysis of computed tomography (CT) term prospective follow-up studies are now awaited to see whether
images of the liver and sonography-based realtime elastography, liver stiffness values can predict the occurrence of clinical events in
which can be performed with conventional ultrasound probes during patients with compensated cirrhosis. If so, TE could be used as a
a routine sonography examination.
51
The theoretical advantages of rapid screening tool to allocate cirrhotic patients to a specific
these methods include the ability to analyse almost the entire liver risk category.
and their applicability to patients with obesity or ascites.
Perspectives
Preliminary results suggested that MR elastography may have a The most rational way of using non-invasive methods in clinical
better diagnostic accuracy than TE for the diagnosis of significant practice is that of a compromise in which non-invasive markers are
fibrosis.
52
Although such results are encouraging, these techniques first used to classify those patients in whom they perform with high
are far too expensive and time-consuming for implementation in accuracy, limiting LB to the subset in whom precise non-invasive
hepatic fibrosis screening. staging is not possible. The respective advantages and
disadvantages of non-invasive methods compared with LB are
Combining Approaches – Transient summarised in Table 2.
Elastography with Serum Markers
TE has certain advantages over indices based on laboratory tests in It is anticipated that non-invasive methods will become an
that it provides more direct measurement of fibrosis and is not important tool in clinical practice. Indeed, the results of a national
affected by intercurrent health disorders. In a study of 183 patients survey in France clearly showed that non-invasive methods are
with CHC where we compared TE with serum fibrosis markers already widely used in routine clinical practice, despite the absence
(FibroTest and APRI) and LB on the same day, the diagnostic of guidelines.
61
However, it is also likely that these markers will
performance of TE was similar to that of FibroTest and APRI.
44
reduce, but not completely abolish, the need for LB.
62
n
However, the combination of TE and FibroTest offered the best
diagnostic performance for both significant fibrosis and cirrhosis.
When TE and FibroTest agreed (which was the case in 70–80% of
Laurent Castera is a Senior Consultant in Hepatology at
Bordeaux University Hospital. His research interests
cases), the results also agreed with those of LB in 84% of cases of
focus on non-invasive assessment of liver fibrosis
significant fibrosis and in 94% of cases of cirrhosis.
(transient elastography and biomarkers), resistance of
hepatitis viruses to antiviral drugs and hepatitis C virus
(HCV)-related steatosis. Dr Castera has authored more
A clinical management algorithm using the combination of TE and
than 60 papers in international peer-reviewed journals,
FibroTest as part of the first-line work-up was inferred from these
is a regular referee for Gastroenterology, Hepatology
results (see
and Gut and is on the Editorial Board of the Journal of
Figure 1). Using this algorithm, LB would have been
Hepatology. He received his MD from the University of Paris VI and his specialism in
avoided for the diagnosis of significant fibrosis in more than 75% of
hepatology and gastroenterology in 1993, and earned his PhD in basic virology from
the patients. Interestingly, the use of either TE or FibroTest has
the laboratory of Professor Pawlotsky.
recently been recommended in France by the Haute Autorité de
46 EUROPEAN GASTROENTEROLOGY & HEPATOLOGY REVIEW
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76