Reviewer ’s report  
 
Title: Comparison o f telbivudine and entecavir on the change of off - treatment eGFR after 3 
years of treatment in non -cirrhotic chronic hepatitis B patients  
 
Version: 0 Date: 11 Jul 2016  
 
Reviewer: Chien -Ning Hsu  
 
Reviewer's report:  
 
This study aimed to compare telbivudine versus entecavir off - treatment effect on the changes in 
eGFR after 3 years of treatment in non -cirrhotic chronic hepatitis B patients  
1. Introduction,  
I don't fully understand the statement, "This reimbursement policy prompted us to conduct and 
observational study…."  
I thought the authors may state how the insurance coverage influ ences treatment decision making 
in Taiwan, and the rationale of comparing telbivudine to ETV (why not other NAs) would 
highlight the importance of the current study.  
 
2. Methods,  
2.1 Please indicate how often the eGFR was measured during the study period. Please specify 
how eGFR was measured at each time point of follow -up, and any strategy was applied to 
deal with missing data and outlier? For instance, if the eGFR analyzed at 1 year follow -up, 
the eGFR or SCr testing results during week 48 -52 weeks can be  analyzed as a mean value at 
that point of time.  
2.2 The authors stated "We investigated the underlying diseases in the beginning of treatment 
including, chronic kidney disease stages, hypertension, diabetes and prescribed potential 
renal toxicity agent s (such as NSAID, immunosuppresive agents)"; however, these potential 
nephrotoxic confounding factors were not adjusted in the regression model. In addition, it 
would be better to differentiate which class of medications with n (%) in the variable of 
"Drug s" in Table 1.  
2.3 In Assessment, the authors defined renal outcomes as "As compared to the baseline, patients 
with an eGFR > 10% was seen as an improvement, whereas, an eGFR< 10% was identified 
as a decline. In patients with an eGFR similar to the baseline were identifi ed as the ones with 
a steady renal function."  The definition is confusing. Please clarify the definition of renal 
outcomes.  
Normally, eGFR following the treatment could  be either higher or lower than the value at 
baseline. One would define changes in eG FR from baseline (eGFRte minus GFR0) divided by 
baseline value (eGFR0) to obtain the change rate (%). Then, one can categorize the rate of eGFR 
change into 3 levels of change: ≥10%, <10%, and between ≥10% and <10% .  
3. Results  
Following the dose adjustmen t by renal function, please present the dosage (e.g. average dose 
over 3 year of treatment)  applied in the study cohort.  
4. Please improve the logic flow of writing in whole manuscript. Further editing is 
recommended. For example, "From some real -world cohort study, …", "The rationale behind 
the maintenance effect after the treatment period is unknown. " What is the maintenance 
effect indicated for?  "Some studies hypothesize that this could be due to the renoprotective 
effects, however, it is still uncl ear and should be clarified in future studies [17]." Only one ref 
is cited.  
Are the methods appropriate and well described?  
If not, please specif y what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Unable to assess  
 
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 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 the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose fi nancially 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 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 you r 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 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: Comparison o f telbivudine and entecavir on the change of off - treatment eGFR after 3 
years of treatment in non -cirrhotic chronic hepatitis B patients  
 
Version: 0 Date: 11 Jul 2016  
 
Reviewer: Chien -Ning Hsu  
 
Reviewer's report:  
 
This study aimed to compare telbivudine versus entecavir off - treatment effect on the changes in 
eGFR after 3 years of treatment in non -cirrhotic chronic hepatitis B patients  
1. Introduction,  
I don't fully understand the statement, "This reimbursement policy prompted us to conduct and 
observational study…."  
I thought the authors may state how the insurance coverage influ ences treatment decision making 
in Taiwan, and the rationale of comparing telbivudine to ETV (why not other NAs) would 
highlight the importance of the current study.  
 
2. Methods,  
2.1 Please indicate how often the eGFR was measured during the study period. Please specify 
how eGFR was measured at each time point of follow -up, and any strategy was applied to 
deal with missing data and outlier? For instance, if the eGFR analyzed at 1 year follow -up, 
the eGFR or SCr testing results during week 48 -52 weeks can be  analyzed as a mean value at 
that point of time.  
2.2 The authors stated "We investigated the underlying diseases in the beginning of treatment 
including, chronic kidney disease stages, hypertension, diabetes and prescribed potential 
renal toxicity agent s (such as NSAID, immunosuppresive agents)"; however, these potential 
nephrotoxic confounding factors were not adjusted in the regression model. In addition, it 
would be better to differentiate which class of medications with n (%) in the variable of 
"Drug s" in Table 1.  
2.3 In Assessment, the authors defined renal outcomes as "As compared to the baseline, patients 
with an eGFR > 10% was seen as an improvement, whereas, an eGFR< 10% was identified 
as a decline. In patients with an eGFR similar to the baseline were identifi ed as the ones with 
a steady renal function."  The definition is confusing. Please clarify the definition of renal 
outcomes.  
Normally, eGFR following the treatment could  be either higher or lower than the value at 
baseline. One would define changes in eG FR from baseline (eGFRte minus GFR0) divided by 
baseline value (eGFR0) to obtain the change rate (%). Then, one can categorize the rate of eGFR 
change into 3 levels of change: ≥10%, <10%, and between ≥10% and <10% .  
3. Results  
Following the dose adjustmen t by renal function, please present the dosage (e.g. average dose 
over 3 year of treatment)  applied in the study cohort.  
4. Please improve the logic flow of writing in whole manuscript. Further editing is 
recommended. For example, "From some real -world cohort study, …", "The rationale behind 
the maintenance effect after the treatment period is unknown. " What is the maintenance 
effect indicated for?  "Some studies hypothesize that this could be due to the renoprotective 
effects, however, it is still uncl ear and should be clarified in future studies [17]." Only one ref 
is cited.  
Are the methods appropriate and well described?  
If not, please specif y what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Unable to assess  
 
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 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 the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose fi nancially 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 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 you r 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 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: Comparison o f telbivudine and entecavir on the change of off - treatment eGFR after 3 
years of treatment in non -cirrhotic chronic hepatitis B patients  
 
Version: 0 Date: 11 Jul 2016  
 
Reviewer: Chien -Ning Hsu  
 
Reviewer's report:  
 
This study aimed to compare telbivudine versus entecavir off - treatment effect on the changes in 
eGFR after 3 years of treatment in non -cirrhotic chronic hepatitis B patients  
1. Introduction,  
I don't fully understand the statement, "This reimbursement policy prompted us to conduct and 
observational study…."  
I thought the authors may state how the insurance coverage influ ences treatment decision making 
in Taiwan, and the rationale of comparing telbivudine to ETV (why not other NAs) would 
highlight the importance of the current study.  
 
2. Methods,  
2.1 Please indicate how often the eGFR was measured during the study period. Please specify 
how eGFR was measured at each time point of follow -up, and any strategy was applied to 
deal with missing data and outlier? For instance, if the eGFR analyzed at 1 year follow -up, 
the eGFR or SCr testing results during week 48 -52 weeks can be  analyzed as a mean value at 
that point of time.  
2.2 The authors stated "We investigated the underlying diseases in the beginning of treatment 
including, chronic kidney disease stages, hypertension, diabetes and prescribed potential 
renal toxicity agent s (such as NSAID, immunosuppresive agents)"; however, these potential 
nephrotoxic confounding factors were not adjusted in the regression model. In addition, it 
would be better to differentiate which class of medications with n (%) in the variable of 
"Drug s" in Table 1.  
2.3 In Assessment, the authors defined renal outcomes as "As compared to the baseline, patients 
with an eGFR > 10% was seen as an improvement, whereas, an eGFR< 10% was identified 
as a decline. In patients with an eGFR similar to the baseline were identifi ed as the ones with 
a steady renal function."  The definition is confusing. Please clarify the definition of renal 
outcomes.  
Normally, eGFR following the treatment could  be either higher or lower than the value at 
baseline. One would define changes in eG FR from baseline (eGFRte minus GFR0) divided by 
baseline value (eGFR0) to obtain the change rate (%). Then, one can categorize the rate of eGFR 
change into 3 levels of change: ≥10%, <10%, and between ≥10% and <10% .  
3. Results  
Following the dose adjustmen t by renal function, please present the dosage (e.g. average dose 
over 3 year of treatment)  applied in the study cohort.  
4. Please improve the logic flow of writing in whole manuscript. Further editing is 
recommended. For example, "From some real -world cohort study, …", "The rationale behind 
the maintenance effect after the treatment period is unknown. " What is the maintenance 
effect indicated for?  "Some studies hypothesize that this could be due to the renoprotective 
effects, however, it is still uncl ear and should be clarified in future studies [17]." Only one ref 
is cited.  
Are the methods appropriate and well described?  
If not, please specif y what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Unable to assess  
 
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 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 the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose fi nancially 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 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 you r 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 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