Title: Uncovering unsuspected advanced liver fibrosis in patients referred to alcohol nurse
specialists using the ELF test
Version: 2 Date: 04 Jan 2021
Reviewer:  Ian Rowe
Reviewer's report:
The authors provide information to inform the use of ELF in patients with diagnosed AUD
in the secondary care setting.  This is a strategy that is endorsed by NICE in England but its
use is not widespread.  The total patient population included (n=99) is not large, amounting to
approximately 2 patients per week, and the definition of the study endpoint requires clarification.
Major points
1.  Total patient population.  The number of patients referred to the alcohol specialist nurse is not
given.  To understand the impact on services and on patient outcomes it would be appropriate
to include the total number of patients referred and subsequently excluded where a diagnosis of
liver disease was established and / or previously made.  It is also noteworthy that the vast majority
of referrals were made from medical specialties yet it is known that alcohol will impact other
specialties - are referrals not routinely received from, for example, trauma and orthopaedics?
2.  Definition of the study endpoint.  The performance characteristics for ELF in the context
of AUD are not discussed.  Since the specificity of ELF in this context is not 100% the study
can only truly define suspected advanced fibrosis and this terminology should be considered
throughout the manuscript.  The highlight remark "1/4 patients in hospital with AUD had
advanced fibrosis" is unlikely to be true when further downstream testing is done and the
discussion of this should include the information provided by Thiele et al (where 21 / 65 patients
with ELF >10.5 did not in fact have advanced fibrosis).
3.  Comparison with other NITs.  The authors include AST:ALT ratio, FIB-4 as proprietary (and
cheaper) tests in the analysis of ELF and show an association of AST:ALT ratio with ELF at the
10.5 cut-off.  The AST:ALT ratio has been previously investigated by Thiele et al, as is referred
to in the discussion, and this warrants further analysis.  How many patients would have been
impacted if this had been used as a rule out test, as suggested in the discussion?  For applicability
in the secondary care setting this could be considered as a triage strategy to allow increased
diagnosis without the need for specialist nurse referral, and indeed an additional and costly test.
4.  Downstream investigation.  The authors state that patients testing positive with ELF will be
offered an appointment with hepatology to consider the need for further investigation, including
transient elastography.  Any test for advanced fibrosis is only as good as the actions that
occur downstream.  In my view, the analysis of ELF in this context is not complete without
an understanding of the impact this had on linkage to specialty care.  How many patients
subsequently attended the offered outpatient review and underwent elastography?  How many
were diagnosed with advanced fibrosis in a specialty clinic?
Minor points
There are occasional errors in the text, e.g. page 12, line 7 - 28/99 patients (29%), where the
percentage doesn't match the numbers.
Several of the figures have text that is very small (and too small to read without zoom to 220+
%).  These should be revised.
Title: Uncovering unsuspected advanced liver fibrosis in patients referred to alcohol nurse
specialists using the ELF test
Version: 2 Date: 04 Jan 2021
Reviewer:  Ian Rowe
Reviewer's report:
The authors provide information to inform the use of ELF in patients with diagnosed AUD
in the secondary care setting.  This is a strategy that is endorsed by NICE in England but its
use is not widespread.  The total patient population included (n=99) is not large, amounting to
approximately 2 patients per week, and the definition of the study endpoint requires clarification.
Major points
1.  Total patient population.  The number of patients referred to the alcohol specialist nurse is not
given.  To understand the impact on services and on patient outcomes it would be appropriate
to include the total number of patients referred and subsequently excluded where a diagnosis of
liver disease was established and / or previously made.  It is also noteworthy that the vast majority
of referrals were made from medical specialties yet it is known that alcohol will impact other
specialties - are referrals not routinely received from, for example, trauma and orthopaedics?
2.  Definition of the study endpoint.  The performance characteristics for ELF in the context
of AUD are not discussed.  Since the specificity of ELF in this context is not 100% the study
can only truly define suspected advanced fibrosis and this terminology should be considered
throughout the manuscript.  The highlight remark "1/4 patients in hospital with AUD had
advanced fibrosis" is unlikely to be true when further downstream testing is done and the
discussion of this should include the information provided by Thiele et al (where 21 / 65 patients
with ELF >10.5 did not in fact have advanced fibrosis).
3.  Comparison with other NITs.  The authors include AST:ALT ratio, FIB-4 as proprietary (and
cheaper) tests in the analysis of ELF and show an association of AST:ALT ratio with ELF at the
10.5 cut-off.  The AST:ALT ratio has been previously investigated by Thiele et al, as is referred
to in the discussion, and this warrants further analysis.  How many patients would have been
impacted if this had been used as a rule out test, as suggested in the discussion?  For applicability
in the secondary care setting this could be considered as a triage strategy to allow increased
diagnosis without the need for specialist nurse referral, and indeed an additional and costly test.
4.  Downstream investigation.  The authors state that patients testing positive with ELF will be
offered an appointment with hepatology to consider the need for further investigation, including
transient elastography.  Any test for advanced fibrosis is only as good as the actions that
occur downstream.  In my view, the analysis of ELF in this context is not complete without
an understanding of the impact this had on linkage to specialty care.  How many patients
subsequently attended the offered outpatient review and underwent elastography?  How many
were diagnosed with advanced fibrosis in a specialty clinic?
Minor points
There are occasional errors in the text, e.g. page 12, line 7 - 28/99 patients (29%), where the
percentage doesn't match the numbers.
Several of the figures have text that is very small (and too small to read without zoom to 220+
%).  These should be revised.
Please review this paper.
user
Title: Uncovering unsuspected advanced liver fibrosis in patients referred to alcohol nurse
specialists using the ELF test
Version: 2 Date: 04 Jan 2021
Reviewer:  Ian Rowe
Reviewer's report:
The authors provide information to inform the use of ELF in patients with diagnosed AUD
in the secondary care setting.  This is a strategy that is endorsed by NICE in England but its
use is not widespread.  The total patient population included (n=99) is not large, amounting to
approximately 2 patients per week, and the definition of the study endpoint requires clarification.
Major points
1.  Total patient population.  The number of patients referred to the alcohol specialist nurse is not
given.  To understand the impact on services and on patient outcomes it would be appropriate
to include the total number of patients referred and subsequently excluded where a diagnosis of
liver disease was established and / or previously made.  It is also noteworthy that the vast majority
of referrals were made from medical specialties yet it is known that alcohol will impact other
specialties - are referrals not routinely received from, for example, trauma and orthopaedics?
2.  Definition of the study endpoint.  The performance characteristics for ELF in the context
of AUD are not discussed.  Since the specificity of ELF in this context is not 100% the study
can only truly define suspected advanced fibrosis and this terminology should be considered
throughout the manuscript.  The highlight remark "1/4 patients in hospital with AUD had
advanced fibrosis" is unlikely to be true when further downstream testing is done and the
discussion of this should include the information provided by Thiele et al (where 21 / 65 patients
with ELF >10.5 did not in fact have advanced fibrosis).
3.  Comparison with other NITs.  The authors include AST:ALT ratio, FIB-4 as proprietary (and
cheaper) tests in the analysis of ELF and show an association of AST:ALT ratio with ELF at the
10.5 cut-off.  The AST:ALT ratio has been previously investigated by Thiele et al, as is referred
to in the discussion, and this warrants further analysis.  How many patients would have been
impacted if this had been used as a rule out test, as suggested in the discussion?  For applicability
in the secondary care setting this could be considered as a triage strategy to allow increased
diagnosis without the need for specialist nurse referral, and indeed an additional and costly test.
4.  Downstream investigation.  The authors state that patients testing positive with ELF will be
offered an appointment with hepatology to consider the need for further investigation, including
transient elastography.  Any test for advanced fibrosis is only as good as the actions that
occur downstream.  In my view, the analysis of ELF in this context is not complete without
an understanding of the impact this had on linkage to specialty care.  How many patients
subsequently attended the offered outpatient review and underwent elastography?  How many
were diagnosed with advanced fibrosis in a specialty clinic?
Minor points
There are occasional errors in the text, e.g. page 12, line 7 - 28/99 patients (29%), where the
percentage doesn't match the numbers.
Several of the figures have text that is very small (and too small to read without zoom to 220+
%).  These should be revised.
assistant