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: 02 Dec 2019  
 
Reviewer: Jerome Guechot  
 
Reviewer's report:  
The authors hav e evaluated the performance of the ELF test in predicting liver -related clinical 
outcomes in postmenopausal women with high alcohol use (≥11 drinks/week) and high BMI 
(25kg/m2). They report a case -control study, nested in a cohort of over 195,000 postmenop ausal 
women. ELF score measured in subjects in whom liver -related event occurred (median delay: 3.8 
years) was compared ELF scores measured in matched controls without liver -related event 
(median follow -up: 9.8 years). ELF tests were retrospectively analyz ed using Serum samples 
stored at -180° C.  
The results show that ELF was significantly higher in cases compared to the controls and in 
cases with shorter time to event. Using cut -off values determined as the point of maximum 
sensibility and specificity on t he ROC curve, time -dependant Cox analysis showed Hazard ratios 
of the order of 2. However, the AUROC for predicting event was poor = 0.583 (95% CI: 0.487 -
0.678).  
The authors concludes, they "have demonstrated the ability of the ELF test to predict clinical ly 
significant liver -related events in middle -aged women with risk factors".  
In the manuscript, the authors detail a well -conducted study. The methods and the results are 
clearly exposed.  
The main criticism that needs to be formulated with respect to this report is that the conclusion 
goes beyond what the results show. As the results show that ELF increases with the risk of 
outcome of a liver -related event, they do not demonstrate that ELF could be used as a predictive 
test in this setting (AUC = 0.583; Dia gnostic accuracy = 26%).  
To show the added value of the ELF test, it would be interesting to compare the ELF score with 
its components and with more accessible tests (for instance: FIB -4). 
The discussion could to be shorter and better focused.  
 
 
 
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.  
 
Not relevant to this manuscript  
 
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. 
 
I declare that I have no competing interests  
 
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: 02 Dec 2019  
 
Reviewer: Jerome Guechot  
 
Reviewer's report:  
The authors hav e evaluated the performance of the ELF test in predicting liver -related clinical 
outcomes in postmenopausal women with high alcohol use (≥11 drinks/week) and high BMI 
(25kg/m2). They report a case -control study, nested in a cohort of over 195,000 postmenop ausal 
women. ELF score measured in subjects in whom liver -related event occurred (median delay: 3.8 
years) was compared ELF scores measured in matched controls without liver -related event 
(median follow -up: 9.8 years). ELF tests were retrospectively analyz ed using Serum samples 
stored at -180° C.  
The results show that ELF was significantly higher in cases compared to the controls and in 
cases with shorter time to event. Using cut -off values determined as the point of maximum 
sensibility and specificity on t he ROC curve, time -dependant Cox analysis showed Hazard ratios 
of the order of 2. However, the AUROC for predicting event was poor = 0.583 (95% CI: 0.487 -
0.678).  
The authors concludes, they "have demonstrated the ability of the ELF test to predict clinical ly 
significant liver -related events in middle -aged women with risk factors".  
In the manuscript, the authors detail a well -conducted study. The methods and the results are 
clearly exposed.  
The main criticism that needs to be formulated with respect to this report is that the conclusion 
goes beyond what the results show. As the results show that ELF increases with the risk of 
outcome of a liver -related event, they do not demonstrate that ELF could be used as a predictive 
test in this setting (AUC = 0.583; Dia gnostic accuracy = 26%).  
To show the added value of the ELF test, it would be interesting to compare the ELF score with 
its components and with more accessible tests (for instance: FIB -4). 
The discussion could to be shorter and better focused.  
 
 
 
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.  
 
Not relevant to this manuscript  
 
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. 
 
I declare that I have no competing interests  
 
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: 02 Dec 2019  
 
Reviewer: Jerome Guechot  
 
Reviewer's report:  
The authors hav e evaluated the performance of the ELF test in predicting liver -related clinical 
outcomes in postmenopausal women with high alcohol use (≥11 drinks/week) and high BMI 
(25kg/m2). They report a case -control study, nested in a cohort of over 195,000 postmenop ausal 
women. ELF score measured in subjects in whom liver -related event occurred (median delay: 3.8 
years) was compared ELF scores measured in matched controls without liver -related event 
(median follow -up: 9.8 years). ELF tests were retrospectively analyz ed using Serum samples 
stored at -180° C.  
The results show that ELF was significantly higher in cases compared to the controls and in 
cases with shorter time to event. Using cut -off values determined as the point of maximum 
sensibility and specificity on t he ROC curve, time -dependant Cox analysis showed Hazard ratios 
of the order of 2. However, the AUROC for predicting event was poor = 0.583 (95% CI: 0.487 -
0.678).  
The authors concludes, they "have demonstrated the ability of the ELF test to predict clinical ly 
significant liver -related events in middle -aged women with risk factors".  
In the manuscript, the authors detail a well -conducted study. The methods and the results are 
clearly exposed.  
The main criticism that needs to be formulated with respect to this report is that the conclusion 
goes beyond what the results show. As the results show that ELF increases with the risk of 
outcome of a liver -related event, they do not demonstrate that ELF could be used as a predictive 
test in this setting (AUC = 0.583; Dia gnostic accuracy = 26%).  
To show the added value of the ELF test, it would be interesting to compare the ELF score with 
its components and with more accessible tests (for instance: FIB -4). 
The discussion could to be shorter and better focused.  
 
 
 
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.  
 
Not relevant to this manuscript  
 
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. 
 
I declare that I have no competing interests  
 
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