Page 15 - NON-INVASIVE TESTS FOR EVALUATION OF LIVER DISEASE SEVERITY AND PROGNOSIS
P. 15
Clinical Practice Guidelines Recommendations
risks of advanced fibrosis and cirrhosis in these patients are usu-
ally below 10% [218].
Recommendations • Screening of liver fibrosis for NAFLD patients is
recommended, particularly among patients with
• TE has better prediction for advanced liver fibrosis and metabolic syndrome or type 2 diabetes mellitus who
cirrhosis than serum biomarkers in chronic hepatitis B have higher risk of liver fibrosis (A1)
(B1)
• Non-invasive assessment including serum biomarkers
• TE is best used to determine liver fibrosis in hepatitis B or TE can be used as first line procedure for the
patients with active viraemia (HBV DNA >2000 IU/ml) identification of patients at low risk of severe fibrosis/
but normal ALT (A1) cirrhosis (A1)
• TE can be used to exclude severe fibrosis and cirrhosis • The identification of significant fibrosis is less accurate
in inactive carriers (HBeAg-negative, low viral load with non-invasive tests as compared to liver biopsy
(HBV DNA <2000 IU/ml) and normal ALT). Liver biopsy and may necessitate, according to the clinical context,
should only be considered in doubtful cases after TE histological confirmation (A1)
(A1)
• Follow-up assessment by either serum biomarkers or
• LS measurement should be interpreted with caution TE for progression of liver fibrosis should be performed
among patients with elevated ALT, and should not be among NAFLD patients at a 3 year interval (B1)
used in patients with very high ALT levels (>10 x ULN)
(A1) Use of non-invasive tests for staging liver disease in other liver
diseases
Use of non-invasive tests for staging liver disease in NAFLD Alcoholic liver disease
Although the use of non-invasive tests in ALD has been explored,
NAFLD is a very common condition with reported prevalence of the methodological quality of existing studies is considerably
approximately 20% in different parts of the world [219,220]. heterogeneous without evaluation in large cohorts of ALD
Simple steatosis does not increase mortality. Fibrosis is the most patients. Existing information on the usefulness of serum
important prognostic factor in NAFLD and is correlated with biomarkers has been recently summarized in the EASL guidelines
liver-related outcomes and mortality [2,221]. Advanced fibrosis, for ALD and in recent reviews [231–233]. While a good perfor-
as determined by non-invasive serum biomarker, has been mance has been reported for the use of FibroTestÒ in detecting
shown to predict liver-related complications and mortality significant fibrosis and cirrhosis (AUROC = 0.84 for F2-F4,
[222,223]. Not all NAFLD patients will develop advanced fibrosis. AUROC = 0.95 for the diagnosis of cirrhosis), APRI has been found
Biopsy series suggested a prevalence of advanced fibrosis in 50% of limited use in the setting of ALD. Of note, FibroMeterÒ and
of NAFLD patients [222], but a population-based study in Hong HepaScoreÒ have shown similar diagnostic accuracies than
Kong revealed only 3.7% of the 264 NAFLD patients had advanced FibroTestÒ [234] with AUROC around 0.80 for significant fibrosis
fibrosis [224]. NAFLD patients with metabolic syndrome and and 0.90 for cirrhosis. In addition, ELFÒ has also been shown to be
those with type 2 diabetes mellitus, had been shown to be at useful in assessing fibrosis in ALD [34]. Interestingly, available
increased risk of having liver fibrosis in both Western and data suggest that serum biomarkers of fibrosis may also be able
Asian cohorts [220,225]. Fibrosis progression is possible among to predict clinical outcomes [234,235].
patients with simple steatosis or non-alcoholic steatohepatitis;
approximately 25% to 37% of patients will have fibrosis progres- Information on elasticity-based techniques, mainly TE, in ALD
sion in 3–5 years [226–228] [229]. Histologic inflammation and is limited due to the scarcity of single-etiology studies. A recent
maybe metabolic factors are associated with higher risk of fibro- systematic review from the Cochrane Collaboration, based on five
sis progression among patients with simple steatosis or steato- retrospective and nine prospective cohort studies with a total of
hepatitis [230]. 834 patients, suggests that TE may be used as a diagnostic
method to rule out severe fibrosis or cirrhosis in patients with
Among the different serum biomarkers studied in NAFLD, only ALD using cut-offs of 9.5 and 12.5 kPa, respectively [236].
NFS and FIB-4 have been externally validated more than once, in However, the authors point out the risk of outcome reporting bias
different NAFLD populations and with consistent results [119]. as well as caution on the use of currently recommended cut-offs
These tests perform best at excluding severe fibrosis-cirrhosis as they are insufficiently validated and because there is the risk of
(with negative predictive values >90%) and could therefore be overestimation of LS values in patients that are not abstinent
used as a first line triage to identify patients at low risk of severe from alcohol consumption.
fibrosis. TE has excellent diagnostic accuracy for cirrhosis with a
higher rate of false positive results than of false negative results Cholestatic liver disease
and higher negative than positive predictive values. Therefore Available information regarding the use of non-invasive tests in
its ability to rule in severe fibrosis-cirrhosis may be insufficient cholestatic diseases is indeed more limited than that for viral
for clinical decision making and may require histological hepatitis and NAFLD. This is due to the fact that patients with
confirmation. these diseases are usually part of cohorts of chronic liver disease
and disease specific data on non-invasive tests performance is
14 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
risks of advanced fibrosis and cirrhosis in these patients are usu-
ally below 10% [218].
Recommendations • Screening of liver fibrosis for NAFLD patients is
recommended, particularly among patients with
• TE has better prediction for advanced liver fibrosis and metabolic syndrome or type 2 diabetes mellitus who
cirrhosis than serum biomarkers in chronic hepatitis B have higher risk of liver fibrosis (A1)
(B1)
• Non-invasive assessment including serum biomarkers
• TE is best used to determine liver fibrosis in hepatitis B or TE can be used as first line procedure for the
patients with active viraemia (HBV DNA >2000 IU/ml) identification of patients at low risk of severe fibrosis/
but normal ALT (A1) cirrhosis (A1)
• TE can be used to exclude severe fibrosis and cirrhosis • The identification of significant fibrosis is less accurate
in inactive carriers (HBeAg-negative, low viral load with non-invasive tests as compared to liver biopsy
(HBV DNA <2000 IU/ml) and normal ALT). Liver biopsy and may necessitate, according to the clinical context,
should only be considered in doubtful cases after TE histological confirmation (A1)
(A1)
• Follow-up assessment by either serum biomarkers or
• LS measurement should be interpreted with caution TE for progression of liver fibrosis should be performed
among patients with elevated ALT, and should not be among NAFLD patients at a 3 year interval (B1)
used in patients with very high ALT levels (>10 x ULN)
(A1) Use of non-invasive tests for staging liver disease in other liver
diseases
Use of non-invasive tests for staging liver disease in NAFLD Alcoholic liver disease
Although the use of non-invasive tests in ALD has been explored,
NAFLD is a very common condition with reported prevalence of the methodological quality of existing studies is considerably
approximately 20% in different parts of the world [219,220]. heterogeneous without evaluation in large cohorts of ALD
Simple steatosis does not increase mortality. Fibrosis is the most patients. Existing information on the usefulness of serum
important prognostic factor in NAFLD and is correlated with biomarkers has been recently summarized in the EASL guidelines
liver-related outcomes and mortality [2,221]. Advanced fibrosis, for ALD and in recent reviews [231–233]. While a good perfor-
as determined by non-invasive serum biomarker, has been mance has been reported for the use of FibroTestÒ in detecting
shown to predict liver-related complications and mortality significant fibrosis and cirrhosis (AUROC = 0.84 for F2-F4,
[222,223]. Not all NAFLD patients will develop advanced fibrosis. AUROC = 0.95 for the diagnosis of cirrhosis), APRI has been found
Biopsy series suggested a prevalence of advanced fibrosis in 50% of limited use in the setting of ALD. Of note, FibroMeterÒ and
of NAFLD patients [222], but a population-based study in Hong HepaScoreÒ have shown similar diagnostic accuracies than
Kong revealed only 3.7% of the 264 NAFLD patients had advanced FibroTestÒ [234] with AUROC around 0.80 for significant fibrosis
fibrosis [224]. NAFLD patients with metabolic syndrome and and 0.90 for cirrhosis. In addition, ELFÒ has also been shown to be
those with type 2 diabetes mellitus, had been shown to be at useful in assessing fibrosis in ALD [34]. Interestingly, available
increased risk of having liver fibrosis in both Western and data suggest that serum biomarkers of fibrosis may also be able
Asian cohorts [220,225]. Fibrosis progression is possible among to predict clinical outcomes [234,235].
patients with simple steatosis or non-alcoholic steatohepatitis;
approximately 25% to 37% of patients will have fibrosis progres- Information on elasticity-based techniques, mainly TE, in ALD
sion in 3–5 years [226–228] [229]. Histologic inflammation and is limited due to the scarcity of single-etiology studies. A recent
maybe metabolic factors are associated with higher risk of fibro- systematic review from the Cochrane Collaboration, based on five
sis progression among patients with simple steatosis or steato- retrospective and nine prospective cohort studies with a total of
hepatitis [230]. 834 patients, suggests that TE may be used as a diagnostic
method to rule out severe fibrosis or cirrhosis in patients with
Among the different serum biomarkers studied in NAFLD, only ALD using cut-offs of 9.5 and 12.5 kPa, respectively [236].
NFS and FIB-4 have been externally validated more than once, in However, the authors point out the risk of outcome reporting bias
different NAFLD populations and with consistent results [119]. as well as caution on the use of currently recommended cut-offs
These tests perform best at excluding severe fibrosis-cirrhosis as they are insufficiently validated and because there is the risk of
(with negative predictive values >90%) and could therefore be overestimation of LS values in patients that are not abstinent
used as a first line triage to identify patients at low risk of severe from alcohol consumption.
fibrosis. TE has excellent diagnostic accuracy for cirrhosis with a
higher rate of false positive results than of false negative results Cholestatic liver disease
and higher negative than positive predictive values. Therefore Available information regarding the use of non-invasive tests in
its ability to rule in severe fibrosis-cirrhosis may be insufficient cholestatic diseases is indeed more limited than that for viral
for clinical decision making and may require histological hepatitis and NAFLD. This is due to the fact that patients with
confirmation. these diseases are usually part of cohorts of chronic liver disease
and disease specific data on non-invasive tests performance is
14 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
