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Non-invasive Assessment of Disease Severity
Table 1: Proposed Indices for Non-invasive Evaluation of Figure 1: Proposed Algorithm for Clinical Practice
Fibrosis in Chronic Liver Diseases Combining FibroScan
®
and FibroTest
®
as First-line
Assessment of Hepatic Fibrosis in Patients with
HCV FibroTest
®
(α-2-macroglobulin, γGT, apolipoprotein A1, haptoglobin,
Chronic Hepatitis C
total bilirubin, age and gender)
16
Forns index (age, platelet count, cholesterol, γGT)
17
HCV RNA detectable
APRI (AST, platelet count)
18
Lok index (platelet count, AST/ALT ratio, INR)
19
FibroScan
FibroSpect
®
(α-2-macroglobulin, hyaluronate, TIMP-1)
20
FibroTest
MP3 (MMP-3, TIMP-1)
21
ELF
®
(age, hyaluronate, MMP-3, TIMP-1)
22
FPI (age, past alcohol intake, AST, cholesterol, HOMA-IR)
23
Do not agree Agree
GUCI (AST, INR, platelet count)
24
Hepascore
®
(bilirubin, γGT, hyaluronate, α-2-macroglobulin, age, sex)
25
Fibrometer
®
(platelet count, prothrombin index, AST, α-2-macroglobulin, Liver biopsy No liver biopsy
hyaluronate, urea, age)
26
Virahep-C model (AST, platelet count, alkaline phosphatase, age)
27
Treatment
Fibroindex (platelet count, AST, gamma-globulin)
28
or follow-up
HBV Zeng (age, a-2-macroglobulin, hyaluronate, γGT)
29
Hui (BMI, bilirubin, platelet count, albumin)
30
No or minimal fibrosis Moderate fibrosis
HCV–HIV SHASTA (hyaluronate, AST, albumin)
31
FibroScan <7.1kPA 7.1 ≤FibroScan
Severe fibrosis-cirrhosis
FIB-4 (age, AST, ALT, platelet count)
32 and <9.5kPA and
FibroScan ≥9.5 and
FibroTest <F2 FibroTest =F2
FibroTest ≥F3
NAFLD NAFLD fibrosis score (NFS) (age, hypeglycaemia, BMI, platelet count,
albumin, AST/ALT ratio)
33
Follow-up Treatment
Treatment
HCV = hepatitis C virus; GT = glytamyl transpeptidase; APRI = aspartate to platelet
Upper GI endoscopy
ratio index; AST = aspartate aminotransferase; ALT = alanine aminotransferase;
US every 6 months
INR = international normalised ratio; TIMP = tissue inhibitor of metalloproteinases;
®
MMP = matrix metalloproteinases; ELF = European Liver Fibrosis score; FPI = fibrosis
probability index; HOMA-IR = homeostasis model assessment of insulin; GUCI = Göteborg
HCV = hepatitis C virus; GI = gastrointestinal; US = ultrasound.
University Cirrhosis Index; HBV = hepatitis B virus; BMI = body mass index; SHASTA = serum 44
Adapted from Castera et al., 2005.
testing for hyaluronate, albumin and AST; NAFLD = non-alcoholic fatty liver disease.
Angers),
26
the FibroSpect II
®
(Promotheus Laboratory Inc., San
Table 2: Respective Advantages and Disadvantages of
Biopsy and Non-invasive Tests for Assessing Liver
Diego),
20
the Enhanced Liver Fibrosis Test [ELF
®
] (iQur Ltd,
Fibrosis in Chronic Disease
Southampton)
22
and the Hepascore
®
(PathWest, University of
Western Australia).
25
Although the diagnostic performance of these
Liver Biopsy Non-invasive Tests
indices is generally good, with areas under the receiver operating
Advantages Direct measure of liver fibrosis Non-invasive
characteristic (ROC) curves ranging from 0.77 to 0.88, their use may Well-established staging system Easy to repeat
be able to confirm or exclude significant fibrosis in fewer than 40% Assessment of architectural Potentially reflects status
of patients with CHC.
36,37
disturbances related to liver fibrosis of entire liver
Evaluation of associated lesions Distinguish extreme ranges
In order to increase diagnostic accuracy, new approaches using
(inflammation, steatosis, iron) of fibrosis
stepwise algorithms combining sequentially different indices have
No risks to patient
No contraindication
recently been proposed.
38
For instance, significant fibrosis could be
Highly performant for
identified with high diagnostic performance (>94% diagnostic
detecting cirrhosis (TE)
accuracy) using aspartate to platelet ratio index (APRI)
18
as a
Combination increases
screening test followed by FibroTest in APRI non-classified cases
diagnostic accuracy
and restricting LB to patients classified as F0–1 by non-invasive
Disadvantages Invasive and painful (10–30%) Indirect measure
tests. Cirrhosis could be identified also with 95% diagnostic (surrogate markers)
accuracy using a similar algorithm combining APRI and FibroTest. Difficult to repeat Failure in 5% of cases (TE)
Overall, LB could have been avoided in around 50 and 80% of cases
Risk of potential life-threatening Unable to discriminate
for the diagnosis of significant fibrosis and cirrhosis, respectively.
complications (0.03%) including between intermediate
mortality (0.01%) stages of fibrosis
Alternative to Serum Markers – Transient
Elastography and Other Imaging Techniques
Contraindicated in presence of Limited availability (TE)
coagulopathy, thrombocytopenia
Recently, transient elastography (TE) (FibroScan
®
, Echosens, Paris)
and ascites
has been proposed for the measure of liver stiffness.
39,40
TE is a
Sampling variability (1/50,000
rapid (less than five minutes) and reproducible technique
41
that can
of the entire liver)
easily be performed at the bedside or in the outpatient clinic, with
Understaging of fibrosis in
immediate results available. They are expressed in kilopascals (kPa), 20% of cases
and range from 2.5 to 75kPa, with normal values around 5kPa.
42
TE = transient elastography.
TE has been shown to be reliable in the assessment of liver fibrosis, with a strong correlation of liver stiffness values with Metavir
initially in patients with CHC
43,44
but also in chronic hepatitis B,
45,46
fibrosis stages and area under the receiver operating characteristic
EUROPEAN GASTROENTEROLOGY & HEPATOLOGY REVIEW 45
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