Reviewer ’s report  
 
Title: Sustained serological and complete responses in HBeAg -Positive Patients treated with  
Peginterferon alfa -2b: a 6 -Year Long -Term Follow -Up of a Multicenter, Randomized, 
Controlled  Trial in China  
 
Version: 1 Date: 25 Feb 2018  
 
Reviewer: Andreas Maieron  
 
Reviewer's report:  
 
I read with interest the report of Jian Sun et al. I believe the paper can give some important 
insight in our current understanding o f who will profit from Peg IFN treatment on the long run 
and therefore this paper represents an important work. However, there are some major criticism:  
 
I believe there is a great bias on the cohort as stated by the authors  - up to one third refused to 
participate in the study - this might be due to fact that they obtained medical treatment 
elsewhere.   
 
* Page 11 lines 25 - 26: For long -term follow -up (LTFU), all subjects were contacted by 
telephone and their continued eligibility was assessed onsite at their local participating centers. 
The subject was included in the LTFU group if he or she was treated in the original study and 
gave informed consent, and had no significant medical conditions precluding the study inclusion.  
 
The authors must stat the exac tly criteria for inclusion and exclusion for this study. E.g. how they 
dealt with patients who where on NA treatment - I guess they have been excluded for LTFU as 
stated on page 21 line 9 - 15. Please provide the exact numbers on how many patients entered the 
LTFU analyses in the flow chart.  
 
* Page 11 line 39 - 47: The investigator assessed clinical signs and symptoms, and complications 
of liver disease (i.e. hepatocellular carcinoma, ascites, variceal bleeding, encephalopathy, 
jaundice, or liver transplant ), and administration of (other) antiviral therapy after the end of the 
initial study.  
 
Please provide the numbers of the clinical events that happened - so the reader can learn about 
the complication rate after PEG - IGN treatment after a mean follow up of  up to six years  
 
* At the end of the long -term follow -up the percentage of patients across treatment groups with 
ALT normalization and who were negative for HBe were 40.7% and 41.3%, respectively, and 
44.4% of patients were receiving HBV antiviral therapy  
 
Please provide information on the patients who were HBe Ag negative and had ALT 
normalisation: how many did receive NA therapy at LTFU and even more important how many 
did not - where there any cases who developed HBe Ag negativity or even seroconversion t hat 
did not receive NA treatment or had a SR or CR at EOS. Was there any HBs Ag decline in the 
patients treated with NA´s   
 
* The authors should include a  analyse of those receiving NA treatment vs those who don't  at 
LTFU at least giving us the numbers a nd indicating the rate of liver related events.  
 
* How many of the pat. who experienced relapse either in the SR or the CR group would qualify 
for treatment    
 
* Please indicate how many of those not getting NA treatment should have gotten one according 
to current e.g. APASL guidelines at LTFU  
 
* Can the authors mention early on treatment predictors of sustainability; please include a 
analysis.  So, we could learn whom to get through a PEG IFN treatment  
 
 
 
 
 
Are the methods appropriate and well described?  
If no t, 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 supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
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 w hat 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 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 fut ure? 
 
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 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 acce pted 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: Sustained serological and complete responses in HBeAg -Positive Patients treated with  
Peginterferon alfa -2b: a 6 -Year Long -Term Follow -Up of a Multicenter, Randomized, 
Controlled  Trial in China  
 
Version: 1 Date: 25 Feb 2018  
 
Reviewer: Andreas Maieron  
 
Reviewer's report:  
 
I read with interest the report of Jian Sun et al. I believe the paper can give some important 
insight in our current understanding o f who will profit from Peg IFN treatment on the long run 
and therefore this paper represents an important work. However, there are some major criticism:  
 
I believe there is a great bias on the cohort as stated by the authors  - up to one third refused to 
participate in the study - this might be due to fact that they obtained medical treatment 
elsewhere.   
 
* Page 11 lines 25 - 26: For long -term follow -up (LTFU), all subjects were contacted by 
telephone and their continued eligibility was assessed onsite at their local participating centers. 
The subject was included in the LTFU group if he or she was treated in the original study and 
gave informed consent, and had no significant medical conditions precluding the study inclusion.  
 
The authors must stat the exac tly criteria for inclusion and exclusion for this study. E.g. how they 
dealt with patients who where on NA treatment - I guess they have been excluded for LTFU as 
stated on page 21 line 9 - 15. Please provide the exact numbers on how many patients entered the 
LTFU analyses in the flow chart.  
 
* Page 11 line 39 - 47: The investigator assessed clinical signs and symptoms, and complications 
of liver disease (i.e. hepatocellular carcinoma, ascites, variceal bleeding, encephalopathy, 
jaundice, or liver transplant ), and administration of (other) antiviral therapy after the end of the 
initial study.  
 
Please provide the numbers of the clinical events that happened - so the reader can learn about 
the complication rate after PEG - IGN treatment after a mean follow up of  up to six years  
 
* At the end of the long -term follow -up the percentage of patients across treatment groups with 
ALT normalization and who were negative for HBe were 40.7% and 41.3%, respectively, and 
44.4% of patients were receiving HBV antiviral therapy  
 
Please provide information on the patients who were HBe Ag negative and had ALT 
normalisation: how many did receive NA therapy at LTFU and even more important how many 
did not - where there any cases who developed HBe Ag negativity or even seroconversion t hat 
did not receive NA treatment or had a SR or CR at EOS. Was there any HBs Ag decline in the 
patients treated with NA´s   
 
* The authors should include a  analyse of those receiving NA treatment vs those who don't  at 
LTFU at least giving us the numbers a nd indicating the rate of liver related events.  
 
* How many of the pat. who experienced relapse either in the SR or the CR group would qualify 
for treatment    
 
* Please indicate how many of those not getting NA treatment should have gotten one according 
to current e.g. APASL guidelines at LTFU  
 
* Can the authors mention early on treatment predictors of sustainability; please include a 
analysis.  So, we could learn whom to get through a PEG IFN treatment  
 
 
 
 
 
Are the methods appropriate and well described?  
If no t, 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 supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
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 w hat 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 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 fut ure? 
 
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 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 acce pted 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: Sustained serological and complete responses in HBeAg -Positive Patients treated with  
Peginterferon alfa -2b: a 6 -Year Long -Term Follow -Up of a Multicenter, Randomized, 
Controlled  Trial in China  
 
Version: 1 Date: 25 Feb 2018  
 
Reviewer: Andreas Maieron  
 
Reviewer's report:  
 
I read with interest the report of Jian Sun et al. I believe the paper can give some important 
insight in our current understanding o f who will profit from Peg IFN treatment on the long run 
and therefore this paper represents an important work. However, there are some major criticism:  
 
I believe there is a great bias on the cohort as stated by the authors  - up to one third refused to 
participate in the study - this might be due to fact that they obtained medical treatment 
elsewhere.   
 
* Page 11 lines 25 - 26: For long -term follow -up (LTFU), all subjects were contacted by 
telephone and their continued eligibility was assessed onsite at their local participating centers. 
The subject was included in the LTFU group if he or she was treated in the original study and 
gave informed consent, and had no significant medical conditions precluding the study inclusion.  
 
The authors must stat the exac tly criteria for inclusion and exclusion for this study. E.g. how they 
dealt with patients who where on NA treatment - I guess they have been excluded for LTFU as 
stated on page 21 line 9 - 15. Please provide the exact numbers on how many patients entered the 
LTFU analyses in the flow chart.  
 
* Page 11 line 39 - 47: The investigator assessed clinical signs and symptoms, and complications 
of liver disease (i.e. hepatocellular carcinoma, ascites, variceal bleeding, encephalopathy, 
jaundice, or liver transplant ), and administration of (other) antiviral therapy after the end of the 
initial study.  
 
Please provide the numbers of the clinical events that happened - so the reader can learn about 
the complication rate after PEG - IGN treatment after a mean follow up of  up to six years  
 
* At the end of the long -term follow -up the percentage of patients across treatment groups with 
ALT normalization and who were negative for HBe were 40.7% and 41.3%, respectively, and 
44.4% of patients were receiving HBV antiviral therapy  
 
Please provide information on the patients who were HBe Ag negative and had ALT 
normalisation: how many did receive NA therapy at LTFU and even more important how many 
did not - where there any cases who developed HBe Ag negativity or even seroconversion t hat 
did not receive NA treatment or had a SR or CR at EOS. Was there any HBs Ag decline in the 
patients treated with NA´s   
 
* The authors should include a  analyse of those receiving NA treatment vs those who don't  at 
LTFU at least giving us the numbers a nd indicating the rate of liver related events.  
 
* How many of the pat. who experienced relapse either in the SR or the CR group would qualify 
for treatment    
 
* Please indicate how many of those not getting NA treatment should have gotten one according 
to current e.g. APASL guidelines at LTFU  
 
* Can the authors mention early on treatment predictors of sustainability; please include a 
analysis.  So, we could learn whom to get through a PEG IFN treatment  
 
 
 
 
 
Are the methods appropriate and well described?  
If no t, 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 supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
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 w hat 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 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 fut ure? 
 
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 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 acce pted 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