Reviewer ’s report  
 
Title: The Association of Hepatitis C Virus Infection Status with Serum Glucose Levels  
 
Version: 1 Date: 06 Aug 2018  
 
Reviewer: Howard D. Strickler  
 
Reviewer's report:  
 
Please include all comments for the authors in this box rather than uploading your report as an 
attachment. Please only upload as attachments annotated versions of manuscripts, graphs, 
supporting materials or other aspects of your report which cannot be in cluded in a text format.  
Please overwrite this text when adding your comments to the authors.The authors were 
responsive to reviewer comments, and the paper is improved over its original version. However, 
there are still a number of items that should be ad dressed before the paper can be deemed ready 
for publication.  
 
Abstract  
The word ALWAYS is not appropriate: "Hepatitis C virus (HCV) infection is ALWAYS 
associated with a disturbance of glucose metabolism"; (ii) Not clear which two groups and 
additionally  confusing since next sentence says the levels were lower: "However, after stopping 
treatment the serum FBG levels were significantly elevated in both groups;" (iii) Relative to 
what reference group: "In sustained responders, fasting insulin (P=0.007), C -peptide (P<0.001) 
and HOMA -IR (P<0.001) were significantly decreased, and the insulin sensitivity index (ISI) 
was increased (P<0.001)". Yes I can figure out what you mean in each of these examples above, 
but it is not neatly written. The conclusions state i mproved insulin hypersecretion, but It is not 
clear how that was determined.  
 
Intro  
How is it "verified" if the data are conflicting: "It has been verified that HCV infection could 
induce insulin resistance (IR)". You say little about prior findings re glucose intolerance and 
HCV that have been reported.  
 
 
Methods  
There is no description o f how the "healty controls" were selected (e.g., were they matched in 
some way to those with HCV? Were they selected as "healthy" in part based on LFTs - if so that 
would make contrasting their results with HCV+s a biased comparison). What determined which  
HCV+ patients were treated? Explain to the reader what HOMA -IR, HOMA -beta, and ISI are 
meant to measure.  
 
Results  
SVR adds up to 101%. Is that due to rounding (then state that) or a typing mistake.  You 
compare SVR to non -SVR but not to untreated. This se ems a missed opportunity. However, the 
authors could frame their paper better to state that they were solely interested in the effects of 
SVR.  
 
Discussion  
(i) What is meant by predisposed:"Previous studies has revealedthat HCV infection causes 
insulin resi stance and glucose abnormalities even type 2 diabetes mellitus(T2DM) in predisposed 
individuals[11, 13]."; (ii) The most likely mechanism for HCV's effects on metabolic factors is 
not mentioned, namely, damage to the liver (e.g., early fibrosis - though pa tients with cirrhosis 
were excluded), which plays a major role in metabolism; (iii) The authors mention statistical 
power but no power calculations are shown. They also call their study large but it is unclear that 
it is among the bigger studies (if it is it needs to be more explicitly stated and referenced); (iv) A 
better explanation for why it is interesting to study older treatment methods (no longer 
"conventional") is the one given in the Introduction, namely, that these methods are still used in 
certai n limited resource settings; (v) The author's extrapolation that "no matter what" that HCV 
clearance will be associated with glucose improvement regardless of the treatment method needs 
to be more cautiously stated, or references given (based on current me thods); (vi). It is unclear 
what data in the study were valid measures beta -cell function (rather than other factors involved 
in impaired fasting glucose).  
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:  
 
Needs some language corrections before being published  
 
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.  
 
None  
 
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: 1 Date: 06 Aug 2018  
 
Reviewer: Howard D. Strickler  
 
Reviewer's report:  
 
Please include all comments for the authors in this box rather than uploading your report as an 
attachment. Please only upload as attachments annotated versions of manuscripts, graphs, 
supporting materials or other aspects of your report which cannot be in cluded in a text format.  
Please overwrite this text when adding your comments to the authors.The authors were 
responsive to reviewer comments, and the paper is improved over its original version. However, 
there are still a number of items that should be ad dressed before the paper can be deemed ready 
for publication.  
 
Abstract  
The word ALWAYS is not appropriate: "Hepatitis C virus (HCV) infection is ALWAYS 
associated with a disturbance of glucose metabolism"; (ii) Not clear which two groups and 
additionally  confusing since next sentence says the levels were lower: "However, after stopping 
treatment the serum FBG levels were significantly elevated in both groups;" (iii) Relative to 
what reference group: "In sustained responders, fasting insulin (P=0.007), C -peptide (P<0.001) 
and HOMA -IR (P<0.001) were significantly decreased, and the insulin sensitivity index (ISI) 
was increased (P<0.001)". Yes I can figure out what you mean in each of these examples above, 
but it is not neatly written. The conclusions state i mproved insulin hypersecretion, but It is not 
clear how that was determined.  
 
Intro  
How is it "verified" if the data are conflicting: "It has been verified that HCV infection could 
induce insulin resistance (IR)". You say little about prior findings re glucose intolerance and 
HCV that have been reported.  
 
 
Methods  
There is no description o f how the "healty controls" were selected (e.g., were they matched in 
some way to those with HCV? Were they selected as "healthy" in part based on LFTs - if so that 
would make contrasting their results with HCV+s a biased comparison). What determined which  
HCV+ patients were treated? Explain to the reader what HOMA -IR, HOMA -beta, and ISI are 
meant to measure.  
 
Results  
SVR adds up to 101%. Is that due to rounding (then state that) or a typing mistake.  You 
compare SVR to non -SVR but not to untreated. This se ems a missed opportunity. However, the 
authors could frame their paper better to state that they were solely interested in the effects of 
SVR.  
 
Discussion  
(i) What is meant by predisposed:"Previous studies has revealedthat HCV infection causes 
insulin resi stance and glucose abnormalities even type 2 diabetes mellitus(T2DM) in predisposed 
individuals[11, 13]."; (ii) The most likely mechanism for HCV's effects on metabolic factors is 
not mentioned, namely, damage to the liver (e.g., early fibrosis - though pa tients with cirrhosis 
were excluded), which plays a major role in metabolism; (iii) The authors mention statistical 
power but no power calculations are shown. They also call their study large but it is unclear that 
it is among the bigger studies (if it is it needs to be more explicitly stated and referenced); (iv) A 
better explanation for why it is interesting to study older treatment methods (no longer 
"conventional") is the one given in the Introduction, namely, that these methods are still used in 
certai n limited resource settings; (v) The author's extrapolation that "no matter what" that HCV 
clearance will be associated with glucose improvement regardless of the treatment method needs 
to be more cautiously stated, or references given (based on current me thods); (vi). It is unclear 
what data in the study were valid measures beta -cell function (rather than other factors involved 
in impaired fasting glucose).  
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:  
 
Needs some language corrections before being published  
 
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.  
 
None  
 
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: 1 Date: 06 Aug 2018  
 
Reviewer: Howard D. Strickler  
 
Reviewer's report:  
 
Please include all comments for the authors in this box rather than uploading your report as an 
attachment. Please only upload as attachments annotated versions of manuscripts, graphs, 
supporting materials or other aspects of your report which cannot be in cluded in a text format.  
Please overwrite this text when adding your comments to the authors.The authors were 
responsive to reviewer comments, and the paper is improved over its original version. However, 
there are still a number of items that should be ad dressed before the paper can be deemed ready 
for publication.  
 
Abstract  
The word ALWAYS is not appropriate: "Hepatitis C virus (HCV) infection is ALWAYS 
associated with a disturbance of glucose metabolism"; (ii) Not clear which two groups and 
additionally  confusing since next sentence says the levels were lower: "However, after stopping 
treatment the serum FBG levels were significantly elevated in both groups;" (iii) Relative to 
what reference group: "In sustained responders, fasting insulin (P=0.007), C -peptide (P<0.001) 
and HOMA -IR (P<0.001) were significantly decreased, and the insulin sensitivity index (ISI) 
was increased (P<0.001)". Yes I can figure out what you mean in each of these examples above, 
but it is not neatly written. The conclusions state i mproved insulin hypersecretion, but It is not 
clear how that was determined.  
 
Intro  
How is it "verified" if the data are conflicting: "It has been verified that HCV infection could 
induce insulin resistance (IR)". You say little about prior findings re glucose intolerance and 
HCV that have been reported.  
 
 
Methods  
There is no description o f how the "healty controls" were selected (e.g., were they matched in 
some way to those with HCV? Were they selected as "healthy" in part based on LFTs - if so that 
would make contrasting their results with HCV+s a biased comparison). What determined which  
HCV+ patients were treated? Explain to the reader what HOMA -IR, HOMA -beta, and ISI are 
meant to measure.  
 
Results  
SVR adds up to 101%. Is that due to rounding (then state that) or a typing mistake.  You 
compare SVR to non -SVR but not to untreated. This se ems a missed opportunity. However, the 
authors could frame their paper better to state that they were solely interested in the effects of 
SVR.  
 
Discussion  
(i) What is meant by predisposed:"Previous studies has revealedthat HCV infection causes 
insulin resi stance and glucose abnormalities even type 2 diabetes mellitus(T2DM) in predisposed 
individuals[11, 13]."; (ii) The most likely mechanism for HCV's effects on metabolic factors is 
not mentioned, namely, damage to the liver (e.g., early fibrosis - though pa tients with cirrhosis 
were excluded), which plays a major role in metabolism; (iii) The authors mention statistical 
power but no power calculations are shown. They also call their study large but it is unclear that 
it is among the bigger studies (if it is it needs to be more explicitly stated and referenced); (iv) A 
better explanation for why it is interesting to study older treatment methods (no longer 
"conventional") is the one given in the Introduction, namely, that these methods are still used in 
certai n limited resource settings; (v) The author's extrapolation that "no matter what" that HCV 
clearance will be associated with glucose improvement regardless of the treatment method needs 
to be more cautiously stated, or references given (based on current me thods); (vi). It is unclear 
what data in the study were valid measures beta -cell function (rather than other factors involved 
in impaired fasting glucose).  
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:  
 
Needs some language corrections before being published  
 
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.  
 
None  
 
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