Reviewer ’s report  
 
Title: Vitamin D -related gene polymorphism predict treatment response to pegylated interferon -
based therapy in Thai chronic hepatitis C patients  
 
Version: 0 Date: 09 Feb 2017  
 
Reviewer: C.-Thomas Bock  
 
Reviewer's report:  
 
Dr Thanapirom and colleagues have presented an interesting observational study in which they 
aimed to determine whether polymorphisms in genes of vitamin D were associated with 
treatment response to IFN/RBV in chronic HCV infected Thai patients. The author s enrolled 623 
Thai patients from 2 university hospitals who were treated with Peg -IFN/RBV for chronic HCV. 
The colleagues analysed known gene polymorphisms of the vitamin D synthetic pathway and 
determined the HCV genotype. As a result of their study the authors concluded that in Thai 
patients with HCV genotype 1 infection the DHCR/ polymorphism were independent predictors 
of improved IFN/RBV treatment outcome and thus could be useful as a predictive marker for 
treatment response.  
Overall, the study is we ll performed and concise in its content showing convincing data. 
However, I have minor comments which should be addressed.  
 
Comments  
1. Because of the importance of vitamin D levels in HCV infected persons; did the colleagues 
determine vitamin D levels of the patients of the study?  
2. Concerning the IFN/RBV therapy, there is no information in terms of duration of treatment 
in the patient groups.  
3. Table 1. I don't understand the last characteristics PEG -IFN-a 2a? Please explain this value.  
4. As a suggest ion for the discussion section, there are very recent and important reports on 
vitamin D and HCV infection contributing to the findings of this study (Wu et al. J Hum 
Genet, 2016,61:129 -135; Hung et al, J Formos Med Assoc 2016; 115:278 -283, and Loftfield 
et al 2016;11:e0166036). Therefore I suggest discussing these studies in the context of the 
results of the colleagues.  
 
 
 
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 auth ors. 
 
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 assess 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 recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscr ipt: 
 
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 n ow 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 t o the content of the manuscript?  
 
5. Do you have any other financial 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 int erests' 
below.  If your reply is yes to any, please give details below.  
 
I declare tha t 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 m anuscript 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 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: Vitamin D -related gene polymorphism predict treatment response to pegylated interferon -
based therapy in Thai chronic hepatitis C patients  
 
Version: 0 Date: 09 Feb 2017  
 
Reviewer: C.-Thomas Bock  
 
Reviewer's report:  
 
Dr Thanapirom and colleagues have presented an interesting observational study in which they 
aimed to determine whether polymorphisms in genes of vitamin D were associated with 
treatment response to IFN/RBV in chronic HCV infected Thai patients. The author s enrolled 623 
Thai patients from 2 university hospitals who were treated with Peg -IFN/RBV for chronic HCV. 
The colleagues analysed known gene polymorphisms of the vitamin D synthetic pathway and 
determined the HCV genotype. As a result of their study the authors concluded that in Thai 
patients with HCV genotype 1 infection the DHCR/ polymorphism were independent predictors 
of improved IFN/RBV treatment outcome and thus could be useful as a predictive marker for 
treatment response.  
Overall, the study is we ll performed and concise in its content showing convincing data. 
However, I have minor comments which should be addressed.  
 
Comments  
1. Because of the importance of vitamin D levels in HCV infected persons; did the colleagues 
determine vitamin D levels of the patients of the study?  
2. Concerning the IFN/RBV therapy, there is no information in terms of duration of treatment 
in the patient groups.  
3. Table 1. I don't understand the last characteristics PEG -IFN-a 2a? Please explain this value.  
4. As a suggest ion for the discussion section, there are very recent and important reports on 
vitamin D and HCV infection contributing to the findings of this study (Wu et al. J Hum 
Genet, 2016,61:129 -135; Hung et al, J Formos Med Assoc 2016; 115:278 -283, and Loftfield 
et al 2016;11:e0166036). Therefore I suggest discussing these studies in the context of the 
results of the colleagues.  
 
 
 
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 auth ors. 
 
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 assess 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 recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscr ipt: 
 
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 n ow 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 t o the content of the manuscript?  
 
5. Do you have any other financial 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 int erests' 
below.  If your reply is yes to any, please give details below.  
 
I declare tha t 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 m anuscript 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 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: Vitamin D -related gene polymorphism predict treatment response to pegylated interferon -
based therapy in Thai chronic hepatitis C patients  
 
Version: 0 Date: 09 Feb 2017  
 
Reviewer: C.-Thomas Bock  
 
Reviewer's report:  
 
Dr Thanapirom and colleagues have presented an interesting observational study in which they 
aimed to determine whether polymorphisms in genes of vitamin D were associated with 
treatment response to IFN/RBV in chronic HCV infected Thai patients. The author s enrolled 623 
Thai patients from 2 university hospitals who were treated with Peg -IFN/RBV for chronic HCV. 
The colleagues analysed known gene polymorphisms of the vitamin D synthetic pathway and 
determined the HCV genotype. As a result of their study the authors concluded that in Thai 
patients with HCV genotype 1 infection the DHCR/ polymorphism were independent predictors 
of improved IFN/RBV treatment outcome and thus could be useful as a predictive marker for 
treatment response.  
Overall, the study is we ll performed and concise in its content showing convincing data. 
However, I have minor comments which should be addressed.  
 
Comments  
1. Because of the importance of vitamin D levels in HCV infected persons; did the colleagues 
determine vitamin D levels of the patients of the study?  
2. Concerning the IFN/RBV therapy, there is no information in terms of duration of treatment 
in the patient groups.  
3. Table 1. I don't understand the last characteristics PEG -IFN-a 2a? Please explain this value.  
4. As a suggest ion for the discussion section, there are very recent and important reports on 
vitamin D and HCV infection contributing to the findings of this study (Wu et al. J Hum 
Genet, 2016,61:129 -135; Hung et al, J Formos Med Assoc 2016; 115:278 -283, and Loftfield 
et al 2016;11:e0166036). Therefore I suggest discussing these studies in the context of the 
results of the colleagues.  
 
 
 
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 auth ors. 
 
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 assess 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 recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscr ipt: 
 
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 n ow 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 t o the content of the manuscript?  
 
5. Do you have any other financial 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 int erests' 
below.  If your reply is yes to any, please give details below.  
 
I declare tha t 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 m anuscript 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 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