Wednesday, April 25, 2012

Non invasive methods

Non-invasive assessment of liver fibrosis based on either
biochemical methods or imaging techniques have emerged over
the past ten years as an alternative to the systematic use of LB.
These methods are easy-to-do, reliable and can be repeated in
follow-up visits. However, these noninvasive tests are more
adequate for identifying patients with advanced
fibrosis/cirrhosis than in differentiating those with moderate
and mild fibrosis. According to the current recommendations,
these methods should not replace LB in routine clinical practice.
Transient elastography (FibroScan™) uses ultrasound and low
frequency elastic waves to measure liver elasticity/stiffness in
kilopascals (kPa).
38 | Hepatitis C Treatment
With a cutoff value of about 7-8 kPa, it can identify about 70% of
patients with histological signs of moderate to severe fibrosis.
With a cutoff of 14-15 kPa, it can identify about 85% of patients
with histological signs of cirrhosis.
Transient elastography is less reliable in ruling out moderate
fibrosis. The results are less certain in patients with a thick chest
wall, hepatic congestion of cardiac origin and acute
exacerbations of hepatitis. However, it has improved the ability
to define the extent of fibrosis without a LB, particularly when
combined with other noninvasive markers.
Biochemical scores are calculated based on panels of multiple
serum markers associated with hepatic fibrosis. Performance of
these measures appears similar in both HCV monoinfected and
HIV-HCV co-infected patients (Shaheen 2008). Several simple
tests are presented in Table 2.5.
Two tests have been specifically designed for HIV-HCV coinfection:
SHASTA index (includes hyaluronic acid, AST and
albumin) (Kelleher 2005) and FIB-4 (ALT and AST level, platelet
count and age) (Sterling 2006).
Table 2.5 – Simple biochemical scores
Test Markers Interpretation
AAR
(Williams 1998)
AST to ALT *ratio AST/ALT ≥ 1: significant
cirrhosis
APRI
(Wai 2003)
AST-platelet ratio APRI < 0.5: no/minimal fibrosis
APRI > 1.5: significant fibrosis
Fibrosis Index (FI)
(Ohta 2006)
Platlet count and serum
albumin
FI < 2.1: no/ minimal fibrosis
FI ≥ 2.1: significant fibrosis
FI ≥ 3.3: cirrhosis
* AST: aspartate aminotransferase; ALT: alanine aminotransferase
Several composite tests based on mathematical algorithms have
been introduced in practice (Table 2.6).
Patients’ monitoring during and after treatment | 39
Table 2.6 – Composite biochemical scores
Test Markers Interpretation
FibroTest™
(Imbert-Bismut 2001)
alpha-2-macroglobulin,
apolipoprotein A1,
haptoglobin, GGT,
bilirubin
Result is provided as a score of 0
to 1, proportional to the severity
of the fibrosis, with conversion
to the METAVIR system (from F0
to F4).
HepaScore™
(Adams 2005)
alpha 2 -macroglobulin
GGT*, bilirubin,
hyaluronic acid, age,
gender
A HepaScore <0.55 is considered
“negative” and indicates a
METAVIR score of F0 or F1.
A HepaScore ≥0.55 is considered
“positive” and indicates a
METAVIR score of F2 to F4.
FibroMeter™
(Cales 2005)
alpha2–macroglobulin,
hyaluronic acid,
platelets, prothrombin
index, AST, urea, age,
gender
FibroMeter™ has two main
diagnostic targets (fibrosis stage
and area of fibrosis), being
adapted for special explicit
causes†.
* GGT: γ-glutamyltranspeptidase
† chronic viral hepatitis B or C, alcoholic liver disease and non-alcoholic fatty
liver disease
FibroTest™ (Biopredictive, Paris, France) identifies about 70% of
patients with histological signs of moderate to severe fibrosis
and about 90% of patients with histological signs of cirrhosis,
using the manufacturers’ recommended cutoff values. The
FibroTest™ together with FibroScan™ have excellent utility for
the identification of HCV-related cirrhosis, but lesser accuracy
for earlier stages (Shaheen 2007).
All these tests are based on routine biochemistry blood assays
and can be influenced by intercurrent conditions. At the same
time, these scores may fluctuate or revert to lower classes after
initial worsening and a dynamic overview is more valuable than
a single determination.
In Europe, the typical approach is to perform a blood test such as
one of the commercially available assays, followed by transient
elastography. If both tests have concordant results on the
disease stage, no biopsy is needed; if there is discordance, biopsy
is performed. New fibrosis indexes combining the biochemical
40 | Hepatitis C Treatment
scores and Fibroscan™ are being developed in order to provide a
more accurate fibrosis stage classificatio

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