Reviewer ’s report  
 
Title: Telbivudine versus Entecavir in Patients with Undetectable Hepatitis B Virus DNA: A 
Randomized Trial  
 
Version: 0 Date: 01 Nov 2016  
 
Reviewer: Glen Lutchman  
 
Reviewer's report:  
 
This is a randomized trail of telbivudine vs entecavir in patients previously treated with entecavir 
and who have high HBsAg titles and undetectable HBV DNA. The rationale is that telbivudine 
which has a high rate of sAg clearance would result in further d ecline in HBsAg titers and 
possibly seroclearance. In addition, using it as mono therapy in patients with very low HBV 
DNA theoretically should avoid breakthrough of resistant mutants, given the low barrier to 
resistance of telbivudine.  
After 48 weeks of t reatment there was no significant difference in sAg titers between the groups 
and no surface antigen loss in either group.  
Almost a quarter of the telbivudine patients experienced vial breakthrough and 15 % developed 
telbivudine resistant mutations.  
 
In principle this was a reasonably well thought out clinical trial.  
1. Was there consideration of comparing entecavir and telbivudine vs telbivudine only (after 48 
weeks of entecavir)?   
2. Would such a study be feasible in eAg negative patients?  
The results  of this study are important in that it demonstrates that this approach of telbivudine 
monotherapy even after viral suppression is not effective in eAg positive patients.  
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 wh ich 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 assess any statistics in the manuscript or would yo u 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 the 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 t he 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 organisat ion 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 reimbursemen ts, 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 competing interests in relation to t his 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 ag ree 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 c omments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Telbivudine versus Entecavir in Patients with Undetectable Hepatitis B Virus DNA: A 
Randomized Trial  
 
Version: 0 Date: 01 Nov 2016  
 
Reviewer: Glen Lutchman  
 
Reviewer's report:  
 
This is a randomized trail of telbivudine vs entecavir in patients previously treated with entecavir 
and who have high HBsAg titles and undetectable HBV DNA. The rationale is that telbivudine 
which has a high rate of sAg clearance would result in further d ecline in HBsAg titers and 
possibly seroclearance. In addition, using it as mono therapy in patients with very low HBV 
DNA theoretically should avoid breakthrough of resistant mutants, given the low barrier to 
resistance of telbivudine.  
After 48 weeks of t reatment there was no significant difference in sAg titers between the groups 
and no surface antigen loss in either group.  
Almost a quarter of the telbivudine patients experienced vial breakthrough and 15 % developed 
telbivudine resistant mutations.  
 
In principle this was a reasonably well thought out clinical trial.  
1. Was there consideration of comparing entecavir and telbivudine vs telbivudine only (after 48 
weeks of entecavir)?   
2. Would such a study be feasible in eAg negative patients?  
The results  of this study are important in that it demonstrates that this approach of telbivudine 
monotherapy even after viral suppression is not effective in eAg positive patients.  
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 wh ich 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 assess any statistics in the manuscript or would yo u 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 the 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 t he 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 organisat ion 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 reimbursemen ts, 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 competing interests in relation to t his 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 ag ree 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 c omments  
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: Telbivudine versus Entecavir in Patients with Undetectable Hepatitis B Virus DNA: A 
Randomized Trial  
 
Version: 0 Date: 01 Nov 2016  
 
Reviewer: Glen Lutchman  
 
Reviewer's report:  
 
This is a randomized trail of telbivudine vs entecavir in patients previously treated with entecavir 
and who have high HBsAg titles and undetectable HBV DNA. The rationale is that telbivudine 
which has a high rate of sAg clearance would result in further d ecline in HBsAg titers and 
possibly seroclearance. In addition, using it as mono therapy in patients with very low HBV 
DNA theoretically should avoid breakthrough of resistant mutants, given the low barrier to 
resistance of telbivudine.  
After 48 weeks of t reatment there was no significant difference in sAg titers between the groups 
and no surface antigen loss in either group.  
Almost a quarter of the telbivudine patients experienced vial breakthrough and 15 % developed 
telbivudine resistant mutations.  
 
In principle this was a reasonably well thought out clinical trial.  
1. Was there consideration of comparing entecavir and telbivudine vs telbivudine only (after 48 
weeks of entecavir)?   
2. Would such a study be feasible in eAg negative patients?  
The results  of this study are important in that it demonstrates that this approach of telbivudine 
monotherapy even after viral suppression is not effective in eAg positive patients.  
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 wh ich 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 assess any statistics in the manuscript or would yo u 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 the 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 t he 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 organisat ion 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 reimbursemen ts, 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 competing interests in relation to t his 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 ag ree 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 c omments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant