Reviewer ’s report  
 
Title: The Enhanced Liver Fibrosis test is associated  with liver -related outcomes in 
postmenopausal women with risk factors for liver disease  
 
Version: 0 Date: 20 Jan 2020  
 
Reviewer: Research Square Reviewer 1  
 
Reviewer's report:  
PEER REVIEWER ASSESSMENTS:  
 
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research 
question(s) (brief or other article types: is there a clear objective)?  
Yes - there is a clear objective  
 
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for the 
objective?  
Yes - the approach is appropriate  
 
EXECUTION - Are the experiments and analyses performed with technical rigor to  allow 
confidence in the results?  
Yes - experiments and analyses were performed appropriately  
 
STATISTICS - Is the use of statistics in the manuscript appropriate?  
Yes - appropriate statistical analyses have been used in the study  
 
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not 
overstated?  
No - there are minor issues  
 
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically 
sound? If not, can revisions be made to make  the work technically sound?  
Probably - with minor revisions  
 
PEER REVIEWER COMMENTS:  
 
GENERAL COMMENTS:  
In this clinical study, the authors provide evidence that stratification by a serum -based enhanced 
liver fibrosis (ELF) score is useful to predict ad verse liver -related events (LRE) in a cohort of 
postmenopausal women with risk -factors for liver diseases. The authors nested their study within 
the UKCTOCS randomized trial and retrospectively analyzed serum samples to correlated ELF 
score with clinical o utcome of patients in a prospectively maintained data base. Though the 
analyzed cohort of patients with LRE is considerably small (n = 58) authors performed case 
control matching to increase sample size and reduce selection bias (total cohort; n = 173). 
Despite advances to detect liver fibrosis and associated diseases early in patients, serum -based 
(non-invasive) methods are highly needed in particular in patients with risk -factors.  
Therefore, the presented results should be of great interest to clinicians  and scientist involved in 
gastro -enterology and hepatology. Despite some minor concerns outlined below, at this stage 
these concerns do not necessarily have to undergo peer -review again.  
 
REQUESTED REVISIONS:  
The authors can be congratulated to this intr iguing clinical study providing evidence that 
stratification by a serum -based enhanced liver fibrosis (ELF) score is useful to predict adverse 
liver-related events (LRE) in a cohort of postmenopausal women with risk -factors for liver 
diseases. The authors nested their study within the UKCTOCS randomized trial and 
retrospectively analyzed serum samples to correlated ELF score with clinical outcome of patients 
in a prospectively maintained data base. Though the analyzed cohort of patients with LRE is 
consider ably small (n = 58) authors performed case control matching to increase sample size and 
reduce selection bias (total cohort; n = 173). I have only have some minor concerns outlined 
below:  
 
 
Minor concerns:  
1. Is there any chance to increase the sample size  or to validate the reported findings within 
an additional patient cohort?  
2. The conclusion on page 12 line 249 that smokers were equally distributed between the 
groups seems to incorrect (compare table 1 on page 14).  
ADDITIONAL REQUESTS/SUGGESTIONS:  
The authors can be congratulated to this intriguing clinical study providing evidence that 
stratification by a serum -based enhanced liver fibrosis (ELF) score is useful to predict adverse 
liver-related events (LRE) in a cohort of postmenopausal women with ris k-factors for liver 
diseases. The authors nested their study within the UKCTOCS randomized trial and 
retrospectively analyzed serum samples to correlated ELF score with clinical outcome of patients 
in a prospectively maintained data base. Though the analyz ed cohort of patients with LRE is 
considerably small (n = 58) authors performed case control matching to increase sample size and 
reduce selection bias (total cohort; n = 173). I have only have some minor concerns outlined 
below:  
 
Minor concerns:  
1. Is there any chance to increase the sample size or to validate the reported findings within 
an additional patient cohort?  
2. The conclusion on page 12 line 249 that smokers were equally distributed between the 
groups seems to incorrect (compare table 1 on page 14). 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of compet ing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents  relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financia l competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have  no competing interests' 
below. If your reply is yes to any, please give details be low. 
 
This reviewer has been recruited by a partner organization, Research Square. Reviewers with 
declared or apparent competing interests are not utilized for these reviews. This reviewer has 
agreed to publication of their comments online under a Creat ive Commons Attribution License 
attributed to Research Square and was paid a small honorarium for  completing the review within 
a specified timeframe. Honoraria for reviews such a s this are paid regardless of the reviewer 
recommendation.  
 
 
 
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any att achments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: The Enhanced Liver Fibrosis test is associated  with liver -related outcomes in 
postmenopausal women with risk factors for liver disease  
 
Version: 0 Date: 20 Jan 2020  
 
Reviewer: Research Square Reviewer 1  
 
Reviewer's report:  
PEER REVIEWER ASSESSMENTS:  
 
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research 
question(s) (brief or other article types: is there a clear objective)?  
Yes - there is a clear objective  
 
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for the 
objective?  
Yes - the approach is appropriate  
 
EXECUTION - Are the experiments and analyses performed with technical rigor to  allow 
confidence in the results?  
Yes - experiments and analyses were performed appropriately  
 
STATISTICS - Is the use of statistics in the manuscript appropriate?  
Yes - appropriate statistical analyses have been used in the study  
 
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not 
overstated?  
No - there are minor issues  
 
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically 
sound? If not, can revisions be made to make  the work technically sound?  
Probably - with minor revisions  
 
PEER REVIEWER COMMENTS:  
 
GENERAL COMMENTS:  
In this clinical study, the authors provide evidence that stratification by a serum -based enhanced 
liver fibrosis (ELF) score is useful to predict ad verse liver -related events (LRE) in a cohort of 
postmenopausal women with risk -factors for liver diseases. The authors nested their study within 
the UKCTOCS randomized trial and retrospectively analyzed serum samples to correlated ELF 
score with clinical o utcome of patients in a prospectively maintained data base. Though the 
analyzed cohort of patients with LRE is considerably small (n = 58) authors performed case 
control matching to increase sample size and reduce selection bias (total cohort; n = 173). 
Despite advances to detect liver fibrosis and associated diseases early in patients, serum -based 
(non-invasive) methods are highly needed in particular in patients with risk -factors.  
Therefore, the presented results should be of great interest to clinicians  and scientist involved in 
gastro -enterology and hepatology. Despite some minor concerns outlined below, at this stage 
these concerns do not necessarily have to undergo peer -review again.  
 
REQUESTED REVISIONS:  
The authors can be congratulated to this intr iguing clinical study providing evidence that 
stratification by a serum -based enhanced liver fibrosis (ELF) score is useful to predict adverse 
liver-related events (LRE) in a cohort of postmenopausal women with risk -factors for liver 
diseases. The authors nested their study within the UKCTOCS randomized trial and 
retrospectively analyzed serum samples to correlated ELF score with clinical outcome of patients 
in a prospectively maintained data base. Though the analyzed cohort of patients with LRE is 
consider ably small (n = 58) authors performed case control matching to increase sample size and 
reduce selection bias (total cohort; n = 173). I have only have some minor concerns outlined 
below:  
 
 
Minor concerns:  
1. Is there any chance to increase the sample size  or to validate the reported findings within 
an additional patient cohort?  
2. The conclusion on page 12 line 249 that smokers were equally distributed between the 
groups seems to incorrect (compare table 1 on page 14).  
ADDITIONAL REQUESTS/SUGGESTIONS:  
The authors can be congratulated to this intriguing clinical study providing evidence that 
stratification by a serum -based enhanced liver fibrosis (ELF) score is useful to predict adverse 
liver-related events (LRE) in a cohort of postmenopausal women with ris k-factors for liver 
diseases. The authors nested their study within the UKCTOCS randomized trial and 
retrospectively analyzed serum samples to correlated ELF score with clinical outcome of patients 
in a prospectively maintained data base. Though the analyz ed cohort of patients with LRE is 
considerably small (n = 58) authors performed case control matching to increase sample size and 
reduce selection bias (total cohort; n = 173). I have only have some minor concerns outlined 
below:  
 
Minor concerns:  
1. Is there any chance to increase the sample size or to validate the reported findings within 
an additional patient cohort?  
2. The conclusion on page 12 line 249 that smokers were equally distributed between the 
groups seems to incorrect (compare table 1 on page 14). 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of compet ing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents  relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financia l competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have  no competing interests' 
below. If your reply is yes to any, please give details be low. 
 
This reviewer has been recruited by a partner organization, Research Square. Reviewers with 
declared or apparent competing interests are not utilized for these reviews. This reviewer has 
agreed to publication of their comments online under a Creat ive Commons Attribution License 
attributed to Research Square and was paid a small honorarium for  completing the review within 
a specified timeframe. Honoraria for reviews such a s this are paid regardless of the reviewer 
recommendation.  
 
 
 
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any att achments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: The Enhanced Liver Fibrosis test is associated  with liver -related outcomes in 
postmenopausal women with risk factors for liver disease  
 
Version: 0 Date: 20 Jan 2020  
 
Reviewer: Research Square Reviewer 1  
 
Reviewer's report:  
PEER REVIEWER ASSESSMENTS:  
 
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research 
question(s) (brief or other article types: is there a clear objective)?  
Yes - there is a clear objective  
 
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for the 
objective?  
Yes - the approach is appropriate  
 
EXECUTION - Are the experiments and analyses performed with technical rigor to  allow 
confidence in the results?  
Yes - experiments and analyses were performed appropriately  
 
STATISTICS - Is the use of statistics in the manuscript appropriate?  
Yes - appropriate statistical analyses have been used in the study  
 
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not 
overstated?  
No - there are minor issues  
 
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically 
sound? If not, can revisions be made to make  the work technically sound?  
Probably - with minor revisions  
 
PEER REVIEWER COMMENTS:  
 
GENERAL COMMENTS:  
In this clinical study, the authors provide evidence that stratification by a serum -based enhanced 
liver fibrosis (ELF) score is useful to predict ad verse liver -related events (LRE) in a cohort of 
postmenopausal women with risk -factors for liver diseases. The authors nested their study within 
the UKCTOCS randomized trial and retrospectively analyzed serum samples to correlated ELF 
score with clinical o utcome of patients in a prospectively maintained data base. Though the 
analyzed cohort of patients with LRE is considerably small (n = 58) authors performed case 
control matching to increase sample size and reduce selection bias (total cohort; n = 173). 
Despite advances to detect liver fibrosis and associated diseases early in patients, serum -based 
(non-invasive) methods are highly needed in particular in patients with risk -factors.  
Therefore, the presented results should be of great interest to clinicians  and scientist involved in 
gastro -enterology and hepatology. Despite some minor concerns outlined below, at this stage 
these concerns do not necessarily have to undergo peer -review again.  
 
REQUESTED REVISIONS:  
The authors can be congratulated to this intr iguing clinical study providing evidence that 
stratification by a serum -based enhanced liver fibrosis (ELF) score is useful to predict adverse 
liver-related events (LRE) in a cohort of postmenopausal women with risk -factors for liver 
diseases. The authors nested their study within the UKCTOCS randomized trial and 
retrospectively analyzed serum samples to correlated ELF score with clinical outcome of patients 
in a prospectively maintained data base. Though the analyzed cohort of patients with LRE is 
consider ably small (n = 58) authors performed case control matching to increase sample size and 
reduce selection bias (total cohort; n = 173). I have only have some minor concerns outlined 
below:  
 
 
Minor concerns:  
1. Is there any chance to increase the sample size  or to validate the reported findings within 
an additional patient cohort?  
2. The conclusion on page 12 line 249 that smokers were equally distributed between the 
groups seems to incorrect (compare table 1 on page 14).  
ADDITIONAL REQUESTS/SUGGESTIONS:  
The authors can be congratulated to this intriguing clinical study providing evidence that 
stratification by a serum -based enhanced liver fibrosis (ELF) score is useful to predict adverse 
liver-related events (LRE) in a cohort of postmenopausal women with ris k-factors for liver 
diseases. The authors nested their study within the UKCTOCS randomized trial and 
retrospectively analyzed serum samples to correlated ELF score with clinical outcome of patients 
in a prospectively maintained data base. Though the analyz ed cohort of patients with LRE is 
considerably small (n = 58) authors performed case control matching to increase sample size and 
reduce selection bias (total cohort; n = 173). I have only have some minor concerns outlined 
below:  
 
Minor concerns:  
1. Is there any chance to increase the sample size or to validate the reported findings within 
an additional patient cohort?  
2. The conclusion on page 12 line 249 that smokers were equally distributed between the 
groups seems to incorrect (compare table 1 on page 14). 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of compet ing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents  relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financia l competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have  no competing interests' 
below. If your reply is yes to any, please give details be low. 
 
This reviewer has been recruited by a partner organization, Research Square. Reviewers with 
declared or apparent competing interests are not utilized for these reviews. This reviewer has 
agreed to publication of their comments online under a Creat ive Commons Attribution License 
attributed to Research Square and was paid a small honorarium for  completing the review within 
a specified timeframe. Honoraria for reviews such a s this are paid regardless of the reviewer 
recommendation.  
 
 
 
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any att achments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant