Title: Uncovering unsuspected advanced liver fibrosis in patients referred to alcohol nurse
specialists using the ELF test
Version: 2 Date: 10 Dec 2020
Reviewer:  Margarita Papatheodoridi
Reviewer's report:
Comments to the authors
This is an interesting study showing that screening with ELF test at could diagnose advanced
liver fibrosis in over 25% of patients with alcohol use disorders (AUD). In particular this was
a study performed by an Alcohol Specialist Nurse and included 99 patients that did not have
a history of liver disease. The authors show that 29% of the patients have high values of ELF
test (>=10.5) and ELF test was not associated with recent alcohol intake or inflammation. The
manuscript focuses on important topic regarding screening of liver disease performed by nurse
in patients with AUD; yet there are some major concerns that would need to be addressed.
Major issues
1. The cohort is quite small (n=99) to have the statistical power to show that the prevalence of
unknown advanced liver fibrosis in AUD patients and have generalizable results.
2. The lack of histological diagnosis of the liver fibrosis is a major limitation as it still represents
the gold standard for assessment of liver fibrosis. However, it is understandable that this is not
available in all patients assessed for liver disease today as non-invasive tests are preferred. The
ELF test has been shown to have excellent accuracy in diagnosing advanced fibrosis in ALD,
but given that it is not widely available outside the UK, validation of the study results should be
performed with other non-invasive methods too. In table 2 the authors present AST/ALT ratio,
FIB4 and APRI score. Perhaps it could be considered determining advanced fibrosis also with
these non-invasive markers, in order to validate the performance of the ELF test. Additionally,
it would be quite interesting if there were any transient elastography data.
3. There is no acknowledgement of the Nurse in the manuscript although it is seems that this
was the main person at the study site performing the ELF test.
4. ELF test should be described in detail in methods section (how it was performed, where, why
this cut-off was used and refs).
5. Since only 3/99 patients had not been drinking up to the point of presentation to the hospital,
this is not enough to provide statistical associations between alcohol consumption and ELF test
values.
6. Tables 1 and 2 should contain all the available patient characteristics and those variables
should be the same in both tables. If not, it should be explained why some are missing (eg. not
enough data in the group of advanced or not advanced fibrosis?). Moreover, those 2 tables could
also be merged in one table. Abbreviations and measuring units of values are missing.
7. Since the cutoff 10.5 of the ELF test was used to diagnose patients with advanced fibrosis,
and binary logistic regression should be more appropriate to investigate factors associated with
advanced fibrosis defined as ELF test >=10.5.
8. It is not very clear what was the rationale of choosing the variables for the multivariable
regression analysis in Table 3 and why this multivariable analysis is different from Table 4.
The authors mention variables were chosen based on logistic regression p-values, but logistic
regression analyses are not presented anywhere in the text or tables.
9. Correlation and comparisons of figure 3 are not enough to prove that there is no “influence
or effect” of age and alcohol consumption on ELF test.
Minor issues
1. Abbreviations need to be defined the first time they appear in the text throughout the
manuscript, as well as in all tables and figure legends.
2. When citing a figure or table, it would be preferable to use “(Figure..)” or “(Table..)” instead
of “(see figure..)” for the better consistency of the text.
3. References need formatting.
4. Figure 1 could be supplementary as it is not very relevant to the main question of the study.
Also, it could be considered to change the chart to a bar chart so that it is more clearly presented.
Again, abbreviations are missing.
5. Figure 2 shows proportion of patients (%) with advanced fibrosis but the y axis title says No
of patients. Advanced fibrosis (ELF >/10.5) needs to be corrected to “(ELF #10.5)”.
6. Supplementary Figure 1 could be a main figure.
Title: Uncovering unsuspected advanced liver fibrosis in patients referred to alcohol nurse
specialists using the ELF test
Version: 2 Date: 10 Dec 2020
Reviewer:  Margarita Papatheodoridi
Reviewer's report:
Comments to the authors
This is an interesting study showing that screening with ELF test at could diagnose advanced
liver fibrosis in over 25% of patients with alcohol use disorders (AUD). In particular this was
a study performed by an Alcohol Specialist Nurse and included 99 patients that did not have
a history of liver disease. The authors show that 29% of the patients have high values of ELF
test (>=10.5) and ELF test was not associated with recent alcohol intake or inflammation. The
manuscript focuses on important topic regarding screening of liver disease performed by nurse
in patients with AUD; yet there are some major concerns that would need to be addressed.
Major issues
1. The cohort is quite small (n=99) to have the statistical power to show that the prevalence of
unknown advanced liver fibrosis in AUD patients and have generalizable results.
2. The lack of histological diagnosis of the liver fibrosis is a major limitation as it still represents
the gold standard for assessment of liver fibrosis. However, it is understandable that this is not
available in all patients assessed for liver disease today as non-invasive tests are preferred. The
ELF test has been shown to have excellent accuracy in diagnosing advanced fibrosis in ALD,
but given that it is not widely available outside the UK, validation of the study results should be
performed with other non-invasive methods too. In table 2 the authors present AST/ALT ratio,
FIB4 and APRI score. Perhaps it could be considered determining advanced fibrosis also with
these non-invasive markers, in order to validate the performance of the ELF test. Additionally,
it would be quite interesting if there were any transient elastography data.
3. There is no acknowledgement of the Nurse in the manuscript although it is seems that this
was the main person at the study site performing the ELF test.
4. ELF test should be described in detail in methods section (how it was performed, where, why
this cut-off was used and refs).
5. Since only 3/99 patients had not been drinking up to the point of presentation to the hospital,
this is not enough to provide statistical associations between alcohol consumption and ELF test
values.
6. Tables 1 and 2 should contain all the available patient characteristics and those variables
should be the same in both tables. If not, it should be explained why some are missing (eg. not
enough data in the group of advanced or not advanced fibrosis?). Moreover, those 2 tables could
also be merged in one table. Abbreviations and measuring units of values are missing.
7. Since the cutoff 10.5 of the ELF test was used to diagnose patients with advanced fibrosis,
and binary logistic regression should be more appropriate to investigate factors associated with
advanced fibrosis defined as ELF test >=10.5.
8. It is not very clear what was the rationale of choosing the variables for the multivariable
regression analysis in Table 3 and why this multivariable analysis is different from Table 4.
The authors mention variables were chosen based on logistic regression p-values, but logistic
regression analyses are not presented anywhere in the text or tables.
9. Correlation and comparisons of figure 3 are not enough to prove that there is no “influence
or effect” of age and alcohol consumption on ELF test.
Minor issues
1. Abbreviations need to be defined the first time they appear in the text throughout the
manuscript, as well as in all tables and figure legends.
2. When citing a figure or table, it would be preferable to use “(Figure..)” or “(Table..)” instead
of “(see figure..)” for the better consistency of the text.
3. References need formatting.
4. Figure 1 could be supplementary as it is not very relevant to the main question of the study.
Also, it could be considered to change the chart to a bar chart so that it is more clearly presented.
Again, abbreviations are missing.
5. Figure 2 shows proportion of patients (%) with advanced fibrosis but the y axis title says No
of patients. Advanced fibrosis (ELF >/10.5) needs to be corrected to “(ELF #10.5)”.
6. Supplementary Figure 1 could be a main figure.
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: 10 Dec 2020
Reviewer:  Margarita Papatheodoridi
Reviewer's report:
Comments to the authors
This is an interesting study showing that screening with ELF test at could diagnose advanced
liver fibrosis in over 25% of patients with alcohol use disorders (AUD). In particular this was
a study performed by an Alcohol Specialist Nurse and included 99 patients that did not have
a history of liver disease. The authors show that 29% of the patients have high values of ELF
test (>=10.5) and ELF test was not associated with recent alcohol intake or inflammation. The
manuscript focuses on important topic regarding screening of liver disease performed by nurse
in patients with AUD; yet there are some major concerns that would need to be addressed.
Major issues
1. The cohort is quite small (n=99) to have the statistical power to show that the prevalence of
unknown advanced liver fibrosis in AUD patients and have generalizable results.
2. The lack of histological diagnosis of the liver fibrosis is a major limitation as it still represents
the gold standard for assessment of liver fibrosis. However, it is understandable that this is not
available in all patients assessed for liver disease today as non-invasive tests are preferred. The
ELF test has been shown to have excellent accuracy in diagnosing advanced fibrosis in ALD,
but given that it is not widely available outside the UK, validation of the study results should be
performed with other non-invasive methods too. In table 2 the authors present AST/ALT ratio,
FIB4 and APRI score. Perhaps it could be considered determining advanced fibrosis also with
these non-invasive markers, in order to validate the performance of the ELF test. Additionally,
it would be quite interesting if there were any transient elastography data.
3. There is no acknowledgement of the Nurse in the manuscript although it is seems that this
was the main person at the study site performing the ELF test.
4. ELF test should be described in detail in methods section (how it was performed, where, why
this cut-off was used and refs).
5. Since only 3/99 patients had not been drinking up to the point of presentation to the hospital,
this is not enough to provide statistical associations between alcohol consumption and ELF test
values.
6. Tables 1 and 2 should contain all the available patient characteristics and those variables
should be the same in both tables. If not, it should be explained why some are missing (eg. not
enough data in the group of advanced or not advanced fibrosis?). Moreover, those 2 tables could
also be merged in one table. Abbreviations and measuring units of values are missing.
7. Since the cutoff 10.5 of the ELF test was used to diagnose patients with advanced fibrosis,
and binary logistic regression should be more appropriate to investigate factors associated with
advanced fibrosis defined as ELF test >=10.5.
8. It is not very clear what was the rationale of choosing the variables for the multivariable
regression analysis in Table 3 and why this multivariable analysis is different from Table 4.
The authors mention variables were chosen based on logistic regression p-values, but logistic
regression analyses are not presented anywhere in the text or tables.
9. Correlation and comparisons of figure 3 are not enough to prove that there is no “influence
or effect” of age and alcohol consumption on ELF test.
Minor issues
1. Abbreviations need to be defined the first time they appear in the text throughout the
manuscript, as well as in all tables and figure legends.
2. When citing a figure or table, it would be preferable to use “(Figure..)” or “(Table..)” instead
of “(see figure..)” for the better consistency of the text.
3. References need formatting.
4. Figure 1 could be supplementary as it is not very relevant to the main question of the study.
Also, it could be considered to change the chart to a bar chart so that it is more clearly presented.
Again, abbreviations are missing.
5. Figure 2 shows proportion of patients (%) with advanced fibrosis but the y axis title says No
of patients. Advanced fibrosis (ELF >/10.5) needs to be corrected to “(ELF #10.5)”.
6. Supplementary Figure 1 could be a main figure.
assistant