Reviewer ’s report  
 
Title: Diagnostic value of alpha -fetoprotein combined with neutrophil -to-lymphocyte ratio for 
hepatocellular carcinoma  
 
Version: 0 Date: 02 Jan 2018  
 
Reviewer: Gerald J. Mizejewski  
 
Reviewer's report:  
 
  This paper represents a well -conceived, -written, and -executed work of clinical diagnostic 
research. The authors have convincingly demonstrate d that, when used in combination, AFP and 
NLR showed the highest sum of sensitivity and specificity  in diagnosing HCC. This 
combination showed the highest area under the ROC curves (0.769) together with higher 
sensitivity (0.767) and a lower specificity ( 0.773) compared to AFP or NLR alone. This 
combination was true among all the two -marker combinations , i.e. AST and ALT with NLR.The 
AFP cutoff was most effective at 24.6 ng/ml rather than 20.0 ng/ml. Moreover the cutoff value of 
AFP at 188.40 ng/ml showed  95 % specificity  when used in combination with other markers.  
This study was needed due to the fact that AFP levels remain normal in 15 -30 % of patients with 
advanced HCC stage disease and increased AFP levels in other liver diseases leading to high 
negative and false -positive rates.  
The authors also provided a nice short review of AFP in HCC using markers such as osteopontin, 
glypican, cavin -2, and others in combination.  
This paper further confirms the use of NLR  as a valuable inexpensive adj unct in combination 
with other cancer markers.  
Are the methods appropriate and well described?  
If not, please specify what is r equired 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, ple ase explain in your comments to the authors.  
 
Yes 
  
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify wh at 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 competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that 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 financial c ompeting 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 below . 
 
I declare that I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments 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 commen ts 
which I do not wish to be included in my named report can be included 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: Diagnostic value of alpha -fetoprotein combined with neutrophil -to-lymphocyte ratio for 
hepatocellular carcinoma  
 
Version: 0 Date: 02 Jan 2018  
 
Reviewer: Gerald J. Mizejewski  
 
Reviewer's report:  
 
  This paper represents a well -conceived, -written, and -executed work of clinical diagnostic 
research. The authors have convincingly demonstrate d that, when used in combination, AFP and 
NLR showed the highest sum of sensitivity and specificity  in diagnosing HCC. This 
combination showed the highest area under the ROC curves (0.769) together with higher 
sensitivity (0.767) and a lower specificity ( 0.773) compared to AFP or NLR alone. This 
combination was true among all the two -marker combinations , i.e. AST and ALT with NLR.The 
AFP cutoff was most effective at 24.6 ng/ml rather than 20.0 ng/ml. Moreover the cutoff value of 
AFP at 188.40 ng/ml showed  95 % specificity  when used in combination with other markers.  
This study was needed due to the fact that AFP levels remain normal in 15 -30 % of patients with 
advanced HCC stage disease and increased AFP levels in other liver diseases leading to high 
negative and false -positive rates.  
The authors also provided a nice short review of AFP in HCC using markers such as osteopontin, 
glypican, cavin -2, and others in combination.  
This paper further confirms the use of NLR  as a valuable inexpensive adj unct in combination 
with other cancer markers.  
Are the methods appropriate and well described?  
If not, please specify what is r equired 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, ple ase explain in your comments to the authors.  
 
Yes 
  
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify wh at 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 competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that 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 financial c ompeting 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 below . 
 
I declare that I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments 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 commen ts 
which I do not wish to be included in my named report can be included 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: Diagnostic value of alpha -fetoprotein combined with neutrophil -to-lymphocyte ratio for 
hepatocellular carcinoma  
 
Version: 0 Date: 02 Jan 2018  
 
Reviewer: Gerald J. Mizejewski  
 
Reviewer's report:  
 
  This paper represents a well -conceived, -written, and -executed work of clinical diagnostic 
research. The authors have convincingly demonstrate d that, when used in combination, AFP and 
NLR showed the highest sum of sensitivity and specificity  in diagnosing HCC. This 
combination showed the highest area under the ROC curves (0.769) together with higher 
sensitivity (0.767) and a lower specificity ( 0.773) compared to AFP or NLR alone. This 
combination was true among all the two -marker combinations , i.e. AST and ALT with NLR.The 
AFP cutoff was most effective at 24.6 ng/ml rather than 20.0 ng/ml. Moreover the cutoff value of 
AFP at 188.40 ng/ml showed  95 % specificity  when used in combination with other markers.  
This study was needed due to the fact that AFP levels remain normal in 15 -30 % of patients with 
advanced HCC stage disease and increased AFP levels in other liver diseases leading to high 
negative and false -positive rates.  
The authors also provided a nice short review of AFP in HCC using markers such as osteopontin, 
glypican, cavin -2, and others in combination.  
This paper further confirms the use of NLR  as a valuable inexpensive adj unct in combination 
with other cancer markers.  
Are the methods appropriate and well described?  
If not, please specify what is r equired 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, ple ase explain in your comments to the authors.  
 
Yes 
  
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify wh at 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 competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that 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 financial c ompeting 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 below . 
 
I declare that I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments 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 commen ts 
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant