Page 20 - NON-INVASIVE TESTS FOR EVALUATION OF LIVER DISEASE SEVERITY AND PROGNOSIS

as a dynamic monitoring tool for risk estimation of HCC
development in patients with chronic hepatitis B. All these results
implied that TE is useful in estimating the risk of HCC development
in patients with chronic liver disease across the etiology despite
different carcinogenetic mechanisms of HCV and HBV.
Based on the close relationship between TE and the risk of
HCC development, several studies have tried to develop and vali-
date LS-based prediction models for HCC development
[310,320,324]. Wong et al. [324] evaluated the accuracy of LS-
HCC score, refined from their previous CU-HCC score [325] in
1555 Asian patients with chronic hepatitis B. The AUROC of LS-
HCC score was higher than that of CU-HCC score in predicting
HCC development (0.83 vs. 0.75 at 3 year, 0.89 vs. 0.81 at 5 year).
More recently, Kim et al. [320] also introduced a predictive model
based on a Cox proportional hazards model using age, male gen-
der, LS value, and HBV DNA in patients with chronic hepatitis B.
This model showed good discrimination capability, with an
AUROC of 0.806 (95% CI 0.738–0.874) and AUROC remained lar-
gely unchanged between iterations, with an average value of
0.802 (95% CI 0.791–0.812). The predicted risk of HCC occurrence
calibrated well with the observed risk, with a correlation coeffi-
cient of 0.905 (p <0.001).
According to all the results regarding non-invasive markers, it
can be concluded that non-invasive methods are not merely an
alternative to biopsy for staging fibrosis, but also predictive of
the incidence of liver-related complications of liver fibrosis,
including HCC development. However, further studies focusing
on diverse etiologies of chronic liver disease, such as ALD or
NAFLD, are needed to expand the clinical prognostic usefulness
of non-invasive methods. In addition, optimal cut-off values with
respect to the different etiologies of chronic liver disease to assess
the risk of HCC development should be set up in subsequent lar-
ger longitudinal prospective studies. In spite of several lim-
itations, non-invasive methods to assess and monitor the risk of
HCC development will help physicians to establish optimum
treatment strategies. It should be further investigated whether
the accuracy of the surveillance strategy can be enhanced, if these
non-invasive methods are incorporated into the routine surveil-
lance strategy.
Recommendations
• Non-invasive tests cannot replace HVPG for a detailed
PH evaluation and upper GI endoscopy for detecting
varices (A1)
• However, in settings where HVPG is not available, TE
could be considered to stratify the risk of CSPH (A2)
• Although TE could be useful to identify patients at risk
of developing HCC, more data are needed before it
can be integrated into an HCC surveillance program
(A1)
Determining prognosis
There is increasing evidence for the prognostic value of non-inva-
sive tests in patients with chronic liver diseases. Several recent
Journal of Hepatology 2015 vol. xxx j xxx–xxx
Please cite this article in press as: EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis. J
Hepatol (2015), http://dx.doi.org/10.1016/j.jhep.2015.04.006
JOURNAL OF HEPATOLOGY
studies have shown that in patients with chronic liver disease,
LS could also predict clinical decompensation as well as survival
[244,268,282,321,322,326,327,328]. For instance, Robic et al.
[322] found that TE was as effective as HVPG in predicting clinical
decompensations in 100 patients with chronic liver disease with
a 2 year follow-up. Both HVPG P10 mmHg and LS P21.1 kPa had
100% NPV for portal-hypertensive complications. Similarly, in a
cohort of 128 Korean patients with active HBV cirrhosis, LS at a
cut-off of 19 kPa, had a hazard ratio of 7 for development of clini-
cal decompensation [321]. In a cohort of 1457 HCV patients, LS
values and FibroTestÒ had the highest 5 year predictive values
for predicting survival and liver-related death, which did not
change after adjustment for treatment response, patient age,
and estimates of necro-inflammatory grade [268]. Interestingly,
Corpechot et al. [244] have shown in 168 patients with PSC that,
not only those with high baseline but also those with increase in
LS values (>1.5 kPa/year) were at a very high risk (approximately
10 times the risk estimated in the other group) of death, liver
transplantation, or hepatic complications within a 4 year period.
In another study in 1025 patients with chronic hepatitis C, the
prognosis of patients with LS between 7 and 14 kPa on inclusion
was significantly impaired when an increase P1 kPa/year was
observed [263].
Finally, it has been recently suggested that SS could predict
the occurrence of complications [329]. Thus the potential of LS
values for predicting clinical outcomes seems to be greater than
that of liver biopsy, probably LS measures ongoing pathophysio-
logical processes and functions that a biopsy cannot.
Similarly, serum biomarkers such as FibroTestÒ [154,234,330],
ELFÒ [235,239], APRI and FIB-4 [222,331], as well as for models
based on standard laboratory tests [332,333] have been shown
to have prognostic value in various chronic liver diseases.
Recommendations
• There is increasing evidence for the prognostic value of
non-invasive tests, particularly LS measurement using
TE, in patients with cirrhosis (A1)
• Increase of LS values over time could be associated
with a worse prognosis in patients with fibrosis or
cirrhosis (A2)
Conflict of interest
Laurent Castera:
– Grant and research support: none
– Advisory Boards: none
– Speaking and teaching: AbbVie, Biopredictive, Bristol-Myers
Squibb, Echosens, Gilead, Merck and Janssen
Henry Lik Yuen Chan:
– Grant and research support: unrestricted grant from Roche
– Advisory Boards: Abbvie, Bristol Myers Squibb, Gilead,
Janssen, Merck, Novartis, Roche
– Speaking and teaching: Abbvie, Bristol Myers Squibb,
Echosens, Gilead, Glaxo-Smith-Kline, Merck, Novartis, Roche
19