Page 3 - NON-INVASIVE TESTS FOR EVALUATION OF LIVER DISEASE SEVERITY AND PROGNOSIS
P. 3
Clinical Practice Guidelines How do serum biomarkers perform for staging liver fibrosis?
Do patented and non-patented serum biomarkers perform
General statements differently?
How does transient elastography (TE) perform for staging
Even though liver biopsy has been used as the reference liver fibrosis?
method for the design, evaluation and validation of How do novel elastography methods perform compared to TE
non-invasive tests, it is an imperfect gold standard. In for staging liver fibrosis?
order to optimize the value of liver biopsy for fibrosis How does TE perform compared to serum biomarkers for stag-
evaluation, it is important to adhere to the following ing liver fibrosis?
recommendations: (i) sample length >15 mm by a 16G What is the added value of combining TE and serum
needle; (ii) use of appropriate scoring systems according biomarkers?
to liver disease etiology; and (iii) reading by an experi- What are the indications for non-invasive tests for staging
enced (and if possible specialized) pathologist. liver disease in viral hepatitis?
What are the indications for non-invasive tests for staging
Non-invasive tests reduce but do not abolish the need for liver disease in non-alcoholic fatty liver disease (NAFLD)?
liver biopsy; they should be used as an integrated system What are the indications for non-invasive tests for staging
with liver biopsy according to the context. liver disease in other chronic liver diseases?
How should non-invasive tests be used when deciding for
Methodology treatment in viral hepatitis?
Is there a use for non-invasive tests when monitoring treat-
These Clinical Practice Guidelines (CPGs) have been developed by ment response in viral hepatitis?
a panel of experts chosen by the EASL and ALEH Governing Is there a use for non-invasive tests when monitoring disease
Boards. The recommendations were peer-reviewed by external progression in chronic liver diseases?
expert reviewers and approved by EASL and ALEH Governing What is the prognostic value of non-invasive tests in chronic
Boards. The CPGs were established using data collected from liver disease?
PubMed and Cochrane database searches. The CPGs have been
based, as far as possible, on evidence from existing publications, Guidelines
and, if evidence was unavailable, the experts’ provide personal
experiences and opinion. When possible, the level of evidence Currently available non-invasive methods
and recommendation are cited. The evidence and recommenda-
tions in these guidelines have been graded according to the Non-invasive methods rely on two different approaches: a ‘‘bio-
Grading of Recommendations Assessment, Development and logical’’ approach based on the quantification of biomarkers in
Evaluation (GRADE) system. The strength of recommendations serum samples or a ‘‘physical’’ approach based on the measure-
thus reflects the quality of underlying evidence. The principles ment of liver stiffness (LS). Although these approaches are com-
of the GRADE system have been enunciated [20]. The quality of plementary, they are based on different rationales. Serum
the evidence in the CPG has been classified into one of three biomarkers indicate several, not strictly liver specific clinical
levels: high (A), moderate (B) or low (C). The GRADE system and serum parameters that have been associated with fibrosis
offers two grades of recommendation: strong (1) or weak (2) stage, as assessed by liver biopsy, whereas LS corresponds to a
(Table 1). The CPGs thus consider the quality of evidence: the genuine and intrinsic physical property of liver parenchyma.
higher the quality of evidence, the more likely a strong recom-
mendation is warranted; the greater the variability in values Serum biomarkers of liver fibrosis
and preferences, or the greater the uncertainty, the more likely
a weaker recommendation is warranted. Many serum biomarkers have been proposed for staging liver
fibrosis, mainly in patients with chronic hepatitis C. They are
The non-invasive tests CPG Panel has considered the following
questions:
What are the currently available non-invasive tests?
What are the endpoints for staging liver fibrosis?
Table 1. Evidence grading used for the EASL-ALEH guidelines (adapted from the GRADE system).
Evidence quality Notes Grading
High A
Moderate Further research is very unlikely to change our confidence in the estimate of effect B
Low Further research is likely to have an important impact on our confidence in the estimate of effect and may C
change the estimate
Recommendation Grading
Strong Further research is very likely to have an important impact on our confidence in the estimate of effect and 1
is likely to change the estimate. Any change of estimate is uncertain
Weak 2
Notes
Factors influencing the strength of the recommendation included the quality of the evidence, presumed
patient-important outcomes, and cost
Variability in preferences and values, or more uncertainty. Recommendation is made with less certainty,
higher cost or resource consumption
2 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
Do patented and non-patented serum biomarkers perform
General statements differently?
How does transient elastography (TE) perform for staging
Even though liver biopsy has been used as the reference liver fibrosis?
method for the design, evaluation and validation of How do novel elastography methods perform compared to TE
non-invasive tests, it is an imperfect gold standard. In for staging liver fibrosis?
order to optimize the value of liver biopsy for fibrosis How does TE perform compared to serum biomarkers for stag-
evaluation, it is important to adhere to the following ing liver fibrosis?
recommendations: (i) sample length >15 mm by a 16G What is the added value of combining TE and serum
needle; (ii) use of appropriate scoring systems according biomarkers?
to liver disease etiology; and (iii) reading by an experi- What are the indications for non-invasive tests for staging
enced (and if possible specialized) pathologist. liver disease in viral hepatitis?
What are the indications for non-invasive tests for staging
Non-invasive tests reduce but do not abolish the need for liver disease in non-alcoholic fatty liver disease (NAFLD)?
liver biopsy; they should be used as an integrated system What are the indications for non-invasive tests for staging
with liver biopsy according to the context. liver disease in other chronic liver diseases?
How should non-invasive tests be used when deciding for
Methodology treatment in viral hepatitis?
Is there a use for non-invasive tests when monitoring treat-
These Clinical Practice Guidelines (CPGs) have been developed by ment response in viral hepatitis?
a panel of experts chosen by the EASL and ALEH Governing Is there a use for non-invasive tests when monitoring disease
Boards. The recommendations were peer-reviewed by external progression in chronic liver diseases?
expert reviewers and approved by EASL and ALEH Governing What is the prognostic value of non-invasive tests in chronic
Boards. The CPGs were established using data collected from liver disease?
PubMed and Cochrane database searches. The CPGs have been
based, as far as possible, on evidence from existing publications, Guidelines
and, if evidence was unavailable, the experts’ provide personal
experiences and opinion. When possible, the level of evidence Currently available non-invasive methods
and recommendation are cited. The evidence and recommenda-
tions in these guidelines have been graded according to the Non-invasive methods rely on two different approaches: a ‘‘bio-
Grading of Recommendations Assessment, Development and logical’’ approach based on the quantification of biomarkers in
Evaluation (GRADE) system. The strength of recommendations serum samples or a ‘‘physical’’ approach based on the measure-
thus reflects the quality of underlying evidence. The principles ment of liver stiffness (LS). Although these approaches are com-
of the GRADE system have been enunciated [20]. The quality of plementary, they are based on different rationales. Serum
the evidence in the CPG has been classified into one of three biomarkers indicate several, not strictly liver specific clinical
levels: high (A), moderate (B) or low (C). The GRADE system and serum parameters that have been associated with fibrosis
offers two grades of recommendation: strong (1) or weak (2) stage, as assessed by liver biopsy, whereas LS corresponds to a
(Table 1). The CPGs thus consider the quality of evidence: the genuine and intrinsic physical property of liver parenchyma.
higher the quality of evidence, the more likely a strong recom-
mendation is warranted; the greater the variability in values Serum biomarkers of liver fibrosis
and preferences, or the greater the uncertainty, the more likely
a weaker recommendation is warranted. Many serum biomarkers have been proposed for staging liver
fibrosis, mainly in patients with chronic hepatitis C. They are
The non-invasive tests CPG Panel has considered the following
questions:
What are the currently available non-invasive tests?
What are the endpoints for staging liver fibrosis?
Table 1. Evidence grading used for the EASL-ALEH guidelines (adapted from the GRADE system).
Evidence quality Notes Grading
High A
Moderate Further research is very unlikely to change our confidence in the estimate of effect B
Low Further research is likely to have an important impact on our confidence in the estimate of effect and may C
change the estimate
Recommendation Grading
Strong Further research is very likely to have an important impact on our confidence in the estimate of effect and 1
is likely to change the estimate. Any change of estimate is uncertain
Weak 2
Notes
Factors influencing the strength of the recommendation included the quality of the evidence, presumed
patient-important outcomes, and cost
Variability in preferences and values, or more uncertainty. Recommendation is made with less certainty,
higher cost or resource consumption
2 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
