Reviewer ’s report  
 
Title: Integrative role of vitamin D related and Interleukin -28B genes polymorphism in 
predicting treatment outcomes of Chronic Hepatitis C  
 
 
Version: 0 Date: 31 Oct 2015  
 
 
Reviewer: Frank Tacke  
 
 
Reviewer's report:  
 
The authors address an important topic, namely whether predictive factors can be identifi ed in 
HCV GT4 patients that allow "low cost" standard IFN/RBV therapy.  
 
1. I assume that IFN/RBV will be only considered an option, if patients have no advanced 
fibrosis. Therefore, I would exclude patients with F4 fibrosis (and in a second model also 
patients with F3 fibrosis) and re -do the analysis. This will be more meaning ful for 
clinical practice.  
 
2. I am unfortunately no expert for the statistics. However, it remained unclear to me 
whether the authors have adequately corrected for confounding variables in their 
multivariate analysis. This manuscript needs to be reassesse d by an independent, 
experienced statistician.  
 
3. I do not understand the factor "numbers of injections" - this will be heaviliy dependent 
on (a) adherence and (b) tolerability of interferon and (c) on -treatment response. All three 
confounders need to be considered separately.  
 
4. The data are likely not normally distributed. Thus, mean/SD cannot be presented, but 
median/range needs to be used.  
 
5. In the discussion or introduction, the authors should quote the updated international 
guidelines for HCV (EAS L / AASLD) that recommend DAAs in GT4 patients. Expert 
guidelines prefer DAAs over "standard therapy" not only for efficacy, but also for 
tolerability.  
 
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 supporte d by the data shown?  
If not, please explain in your comments to the authors.  
 
Unable to assess  
 
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 spe cify what aspects require further  
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being pub lished  
 
Declaration of competing interests  
Please comp lete 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 t his 
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 apply ing 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 fina ncial 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 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 ac cepted 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 licen se (http://creativecommo ns.org/licenses/by/4.0/ ). I understand that any comments  
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: Integrative role of vitamin D related and Interleukin -28B genes polymorphism in 
predicting treatment outcomes of Chronic Hepatitis C  
 
 
Version: 0 Date: 31 Oct 2015  
 
 
Reviewer: Frank Tacke  
 
 
Reviewer's report:  
 
The authors address an important topic, namely whether predictive factors can be identifi ed in 
HCV GT4 patients that allow "low cost" standard IFN/RBV therapy.  
 
1. I assume that IFN/RBV will be only considered an option, if patients have no advanced 
fibrosis. Therefore, I would exclude patients with F4 fibrosis (and in a second model also 
patients with F3 fibrosis) and re -do the analysis. This will be more meaning ful for 
clinical practice.  
 
2. I am unfortunately no expert for the statistics. However, it remained unclear to me 
whether the authors have adequately corrected for confounding variables in their 
multivariate analysis. This manuscript needs to be reassesse d by an independent, 
experienced statistician.  
 
3. I do not understand the factor "numbers of injections" - this will be heaviliy dependent 
on (a) adherence and (b) tolerability of interferon and (c) on -treatment response. All three 
confounders need to be considered separately.  
 
4. The data are likely not normally distributed. Thus, mean/SD cannot be presented, but 
median/range needs to be used.  
 
5. In the discussion or introduction, the authors should quote the updated international 
guidelines for HCV (EAS L / AASLD) that recommend DAAs in GT4 patients. Expert 
guidelines prefer DAAs over "standard therapy" not only for efficacy, but also for 
tolerability.  
 
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 supporte d by the data shown?  
If not, please explain in your comments to the authors.  
 
Unable to assess  
 
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 spe cify what aspects require further  
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being pub lished  
 
Declaration of competing interests  
Please comp lete 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 t his 
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 apply ing 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 fina ncial 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 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 ac cepted 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 licen se (http://creativecommo ns.org/licenses/by/4.0/ ). I understand that any comments  
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: Integrative role of vitamin D related and Interleukin -28B genes polymorphism in 
predicting treatment outcomes of Chronic Hepatitis C  
 
 
Version: 0 Date: 31 Oct 2015  
 
 
Reviewer: Frank Tacke  
 
 
Reviewer's report:  
 
The authors address an important topic, namely whether predictive factors can be identifi ed in 
HCV GT4 patients that allow "low cost" standard IFN/RBV therapy.  
 
1. I assume that IFN/RBV will be only considered an option, if patients have no advanced 
fibrosis. Therefore, I would exclude patients with F4 fibrosis (and in a second model also 
patients with F3 fibrosis) and re -do the analysis. This will be more meaning ful for 
clinical practice.  
 
2. I am unfortunately no expert for the statistics. However, it remained unclear to me 
whether the authors have adequately corrected for confounding variables in their 
multivariate analysis. This manuscript needs to be reassesse d by an independent, 
experienced statistician.  
 
3. I do not understand the factor "numbers of injections" - this will be heaviliy dependent 
on (a) adherence and (b) tolerability of interferon and (c) on -treatment response. All three 
confounders need to be considered separately.  
 
4. The data are likely not normally distributed. Thus, mean/SD cannot be presented, but 
median/range needs to be used.  
 
5. In the discussion or introduction, the authors should quote the updated international 
guidelines for HCV (EAS L / AASLD) that recommend DAAs in GT4 patients. Expert 
guidelines prefer DAAs over "standard therapy" not only for efficacy, but also for 
tolerability.  
 
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 supporte d by the data shown?  
If not, please explain in your comments to the authors.  
 
Unable to assess  
 
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 spe cify what aspects require further  
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being pub lished  
 
Declaration of competing interests  
Please comp lete 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 t his 
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 apply ing 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 fina ncial 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 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 ac cepted 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 licen se (http://creativecommo ns.org/licenses/by/4.0/ ). I understand that any comments  
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