Reviewer ’s report  
 
Title: The Association of Hepatitis C Virus Infection Status with Serum Glucose Levels  
 
Version: 0 Date: 10 Nov 2017  
 
Reviewer: Howard D. Strickler  
 
Reviewer's report:  
 
This study of 183 HCV+ subjects examined fasting blood glucose (FBG) and other regulatory 
components of glucose met abolism before and after treatment with interferon and ribavirin; i.e., 
at baseline (prior to treatment), at the end of treatment, and 24 weeks post treatment.  Patients 
with HBV, cirrhosis, or diabetes were excluded. All 183 treated HCV+s had >80% adheren ce 
with treatment, and were analyzed. HCV+s had higher FBG than 325 normal controls at 
baseline. FBG levels in HCV+ subjects were significantly reduced following treatment 
regardless of sustained viral responders (SVR), whereas insulin, C -peptide, and HOMA -IR were 
significantly reduced in SVR but not non -responders.   
This is an interesting study of HCV and the impact of treatment on glucose metabolism. The 
prospective design is a major strength, and the paper is generally well written.  
There are however  some limitations that should be addressed and/or acknowledged. Changes in 
glucose results over time are mentioned in the Abstract, though are confusingly written. In 
addition, the serial FBG data are not presented results, though they are shown in the tab les.  That 
should be addressed. The analysis currently focuses on the impact of FBG on SVR, but should 
also examine the impact of SVR on FBG in appropriate multivariate models, as well as how 
change in FBG/insulin/HOMA -IR correlated with changes in liver d isease markers, including 
ALT/AST, or whether HCV genotype influenced the findings amongst those with SVR. The 
multivariate models should include interaction terms for SVR to assess the relative contribution 
of starting FBG or HOMA -IR, baseline HCV viral o r liver disease markers, versus SVR itself, on 
subsequent FBG and HOMA -IR at 24 weeks.  
The Discussion fails to mention the many glucose metabolism proteins and inflammatory factors 
that are produced in the liver that could contribute to impact of HCV on glucose metabolism, as 
well as other important functions of the liver in metabolism. The paper also does not mention the 
extent of prior papers that have shown changes in FBG and glucose metabolism following SVR. 
Lastly, the treatment used is no longer sta te of the art, as targeted therapies are available and it 
would be interesting to know the impact of these now conventional methods on metabolic 
endpoints. That should be acknowledged as a limitation in the Discussion.  
  
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 t he 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.  
 
Yes 
 
Are you able to ass ess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess th e 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 p ast 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 competing interests?  
 
6. Do you have any non -financial com peting 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 alon g 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 repor t 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: The Association of Hepatitis C Virus Infection Status with Serum Glucose Levels  
 
Version: 0 Date: 10 Nov 2017  
 
Reviewer: Howard D. Strickler  
 
Reviewer's report:  
 
This study of 183 HCV+ subjects examined fasting blood glucose (FBG) and other regulatory 
components of glucose met abolism before and after treatment with interferon and ribavirin; i.e., 
at baseline (prior to treatment), at the end of treatment, and 24 weeks post treatment.  Patients 
with HBV, cirrhosis, or diabetes were excluded. All 183 treated HCV+s had >80% adheren ce 
with treatment, and were analyzed. HCV+s had higher FBG than 325 normal controls at 
baseline. FBG levels in HCV+ subjects were significantly reduced following treatment 
regardless of sustained viral responders (SVR), whereas insulin, C -peptide, and HOMA -IR were 
significantly reduced in SVR but not non -responders.   
This is an interesting study of HCV and the impact of treatment on glucose metabolism. The 
prospective design is a major strength, and the paper is generally well written.  
There are however  some limitations that should be addressed and/or acknowledged. Changes in 
glucose results over time are mentioned in the Abstract, though are confusingly written. In 
addition, the serial FBG data are not presented results, though they are shown in the tab les.  That 
should be addressed. The analysis currently focuses on the impact of FBG on SVR, but should 
also examine the impact of SVR on FBG in appropriate multivariate models, as well as how 
change in FBG/insulin/HOMA -IR correlated with changes in liver d isease markers, including 
ALT/AST, or whether HCV genotype influenced the findings amongst those with SVR. The 
multivariate models should include interaction terms for SVR to assess the relative contribution 
of starting FBG or HOMA -IR, baseline HCV viral o r liver disease markers, versus SVR itself, on 
subsequent FBG and HOMA -IR at 24 weeks.  
The Discussion fails to mention the many glucose metabolism proteins and inflammatory factors 
that are produced in the liver that could contribute to impact of HCV on glucose metabolism, as 
well as other important functions of the liver in metabolism. The paper also does not mention the 
extent of prior papers that have shown changes in FBG and glucose metabolism following SVR. 
Lastly, the treatment used is no longer sta te of the art, as targeted therapies are available and it 
would be interesting to know the impact of these now conventional methods on metabolic 
endpoints. That should be acknowledged as a limitation in the Discussion.  
  
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 t he 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.  
 
Yes 
 
Are you able to ass ess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess th e 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 p ast 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 competing interests?  
 
6. Do you have any non -financial com peting 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 alon g 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 repor t 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: The Association of Hepatitis C Virus Infection Status with Serum Glucose Levels  
 
Version: 0 Date: 10 Nov 2017  
 
Reviewer: Howard D. Strickler  
 
Reviewer's report:  
 
This study of 183 HCV+ subjects examined fasting blood glucose (FBG) and other regulatory 
components of glucose met abolism before and after treatment with interferon and ribavirin; i.e., 
at baseline (prior to treatment), at the end of treatment, and 24 weeks post treatment.  Patients 
with HBV, cirrhosis, or diabetes were excluded. All 183 treated HCV+s had >80% adheren ce 
with treatment, and were analyzed. HCV+s had higher FBG than 325 normal controls at 
baseline. FBG levels in HCV+ subjects were significantly reduced following treatment 
regardless of sustained viral responders (SVR), whereas insulin, C -peptide, and HOMA -IR were 
significantly reduced in SVR but not non -responders.   
This is an interesting study of HCV and the impact of treatment on glucose metabolism. The 
prospective design is a major strength, and the paper is generally well written.  
There are however  some limitations that should be addressed and/or acknowledged. Changes in 
glucose results over time are mentioned in the Abstract, though are confusingly written. In 
addition, the serial FBG data are not presented results, though they are shown in the tab les.  That 
should be addressed. The analysis currently focuses on the impact of FBG on SVR, but should 
also examine the impact of SVR on FBG in appropriate multivariate models, as well as how 
change in FBG/insulin/HOMA -IR correlated with changes in liver d isease markers, including 
ALT/AST, or whether HCV genotype influenced the findings amongst those with SVR. The 
multivariate models should include interaction terms for SVR to assess the relative contribution 
of starting FBG or HOMA -IR, baseline HCV viral o r liver disease markers, versus SVR itself, on 
subsequent FBG and HOMA -IR at 24 weeks.  
The Discussion fails to mention the many glucose metabolism proteins and inflammatory factors 
that are produced in the liver that could contribute to impact of HCV on glucose metabolism, as 
well as other important functions of the liver in metabolism. The paper also does not mention the 
extent of prior papers that have shown changes in FBG and glucose metabolism following SVR. 
Lastly, the treatment used is no longer sta te of the art, as targeted therapies are available and it 
would be interesting to know the impact of these now conventional methods on metabolic 
endpoints. That should be acknowledged as a limitation in the Discussion.  
  
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 t he 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.  
 
Yes 
 
Are you able to ass ess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess th e 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 p ast 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 competing interests?  
 
6. Do you have any non -financial com peting 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 alon g 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 repor t 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