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: 03 Mar 2018  
 
Reviewer: Michael Gschwantler  
 
Reviewer's report:  
 
At present only a limited number of studies assessing the long -term outcome of treatment of 
chronic hepatitis B with peginterferon have been published and their res ults have been 
conflicting. Therefore the authors have to be congratulated for presenting there date from a large 
Chinese cohort. In general, the paper is well written.  
 
As presented in Table 2, the rates of sustainability of serological response and combi ned 
response were not significantly different between the three treatment regimens, although the 
rates were numerically higher in the 48 -week treatment group. Therefore, the final sentence of 
the paper, stating "Patients treated with 1,5 mikrogram/kg/wk fo r 48 weeks had significantly 
higher rates of sustained SR and CR" is not correct or could be misunderstood. It would be 
correct to state that "The six year cumulative response rate was significantly higher in the 48 -
week treatmebt group as compared to the two other treatment groups".  
 
It is difficult to interpret the six -year cumulative response rates. For example the six -year 
cumulative combined response rate was 70% in the 48 -week treatment group (see table 2). 
However, 47.7% of patients in this group had  received additional antiviral treatment during long -
term follow -up (see Table 1). Therefore the 70% six -year cumulative combined response rate is 
not only an effect of the original peginterferon -therapy but also of the additional antiviral 
treatment durin g long -term follow -up. I would like to know, how many patients, who had NOT 
achieved serological or combined response at the end of the original study, had achieved these 
endpoints WITHOUT further antiviral therapy at the end of long -term follow -up. (It ha s been 
reported that response rates increase even after six months after end of interferon treatment).  
 
In Table 1 the rates of HBe seroconversion are given for the time points EOT and EOS, but not 
for the time point end of long -term follow -up. 
Are the meth ods 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 c onclusions 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 statistica l 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:  
 
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 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 f or 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 aut hors 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 re view 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: 03 Mar 2018  
 
Reviewer: Michael Gschwantler  
 
Reviewer's report:  
 
At present only a limited number of studies assessing the long -term outcome of treatment of 
chronic hepatitis B with peginterferon have been published and their res ults have been 
conflicting. Therefore the authors have to be congratulated for presenting there date from a large 
Chinese cohort. In general, the paper is well written.  
 
As presented in Table 2, the rates of sustainability of serological response and combi ned 
response were not significantly different between the three treatment regimens, although the 
rates were numerically higher in the 48 -week treatment group. Therefore, the final sentence of 
the paper, stating "Patients treated with 1,5 mikrogram/kg/wk fo r 48 weeks had significantly 
higher rates of sustained SR and CR" is not correct or could be misunderstood. It would be 
correct to state that "The six year cumulative response rate was significantly higher in the 48 -
week treatmebt group as compared to the two other treatment groups".  
 
It is difficult to interpret the six -year cumulative response rates. For example the six -year 
cumulative combined response rate was 70% in the 48 -week treatment group (see table 2). 
However, 47.7% of patients in this group had  received additional antiviral treatment during long -
term follow -up (see Table 1). Therefore the 70% six -year cumulative combined response rate is 
not only an effect of the original peginterferon -therapy but also of the additional antiviral 
treatment durin g long -term follow -up. I would like to know, how many patients, who had NOT 
achieved serological or combined response at the end of the original study, had achieved these 
endpoints WITHOUT further antiviral therapy at the end of long -term follow -up. (It ha s been 
reported that response rates increase even after six months after end of interferon treatment).  
 
In Table 1 the rates of HBe seroconversion are given for the time points EOT and EOS, but not 
for the time point end of long -term follow -up. 
Are the meth ods 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 c onclusions 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 statistica l 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:  
 
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 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 f or 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 aut hors 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 re view 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: 03 Mar 2018  
 
Reviewer: Michael Gschwantler  
 
Reviewer's report:  
 
At present only a limited number of studies assessing the long -term outcome of treatment of 
chronic hepatitis B with peginterferon have been published and their res ults have been 
conflicting. Therefore the authors have to be congratulated for presenting there date from a large 
Chinese cohort. In general, the paper is well written.  
 
As presented in Table 2, the rates of sustainability of serological response and combi ned 
response were not significantly different between the three treatment regimens, although the 
rates were numerically higher in the 48 -week treatment group. Therefore, the final sentence of 
the paper, stating "Patients treated with 1,5 mikrogram/kg/wk fo r 48 weeks had significantly 
higher rates of sustained SR and CR" is not correct or could be misunderstood. It would be 
correct to state that "The six year cumulative response rate was significantly higher in the 48 -
week treatmebt group as compared to the two other treatment groups".  
 
It is difficult to interpret the six -year cumulative response rates. For example the six -year 
cumulative combined response rate was 70% in the 48 -week treatment group (see table 2). 
However, 47.7% of patients in this group had  received additional antiviral treatment during long -
term follow -up (see Table 1). Therefore the 70% six -year cumulative combined response rate is 
not only an effect of the original peginterferon -therapy but also of the additional antiviral 
treatment durin g long -term follow -up. I would like to know, how many patients, who had NOT 
achieved serological or combined response at the end of the original study, had achieved these 
endpoints WITHOUT further antiviral therapy at the end of long -term follow -up. (It ha s been 
reported that response rates increase even after six months after end of interferon treatment).  
 
In Table 1 the rates of HBe seroconversion are given for the time points EOT and EOS, but not 
for the time point end of long -term follow -up. 
Are the meth ods 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 c onclusions 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 statistica l 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:  
 
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 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 f or 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 aut hors 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 re view policy of the journal  
assistant