Reviewer ’s report  
 
Title: Cumulative Incidence of Hepatocellular Carcinoma and Hep atitis B Surface Antigen 
Seroclearance after Nucleos(t)ide analogue -induced Hepatitis B e Antigen Seroclearance  
 
Version: 0 Date: 19 Nov 2019  
 
Reviewer: Monica Robotin  
 
Reviewer's report:  
 
This paper ascertained HCC risk in patients who seroconverted from HBeAg positive to HBeAb 
positive while receiving chronic hepatitis B treatment with nucleos(t)ide analogues (NA); the 
cumulative rate of he patitis B surface antigen (HBsAg) clearance was also ascertained during 
follow up.  
 
I am seeking some points of clarification from the authors:  
 
1. Abstract: under Methods - I assume that all patients had chronic hepatitis B infection - 
i.e. they were all HBs Ag positive? Perhaps this sentence could be rephrased for clarity?  
 
2. Background: reference is made to discontinuing NAs after ≥12 months of consolidation 
therapy in patients who on treatment. Is this the strategy employed in this patient 
cohort?  Under "a ntiviral therapy" it is stated that all but 12 patients continued on 
antiviral therapy after 12 months of being HBeAg negative - i.e. do all seroconverting 
patients continue NAs indefinitely?  
 
3. Methods: It is unclear how the 203 study patients were selecte d. I assume they were all 
HBsAg positive (not HBsAg negative) to qualify for treatment? What was the study 
period and were all patients who underwent HBeAg seroconversion on treatment 
included (except for those with the stated exclusion criteria)?  
 
4. What  was the loss to follow up and how was that handled?  
 
5. Was there a difference in outcome in patients who had entecavir or tenofovir as first 
line, or as rescue therapy?  
 
6. Statistical analysis: please clarify following sentence: "chi -square and Fisher's e xact 
test were used to compare qualitative variables".  
 
7. The Discussion section needs more structure. For example the first para - some of the 
information needs to be included in Results.  
 
8. The Discussion would benefit from placing these results in the context of available 
literature and emphasizing the contribution made by the study to the body of 
knowledge in this area.  
Are the metho ds 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 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 manus cript or would you recommend an 
additional statistical review?  
If an additional s tatistical review is recommended, please speci fy 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 manuscript:  
 
Accept able 
 
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, f ees, funding, or salary 
from an organisation that may in any way  gain or lose financial ly from the 
publication of this manuscript, either now or in the future?  
 
2.  Do you hold any stocks or shares in an organisation t hat may in any way gain or 
lose financially from the publication of this manuscript, either now or in th e 
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 conte nt 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 understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or 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 Acc ess 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 in cluded 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: Cumulative Incidence of Hepatocellular Carcinoma and Hep atitis B Surface Antigen 
Seroclearance after Nucleos(t)ide analogue -induced Hepatitis B e Antigen Seroclearance  
 
Version: 0 Date: 19 Nov 2019  
 
Reviewer: Monica Robotin  
 
Reviewer's report:  
 
This paper ascertained HCC risk in patients who seroconverted from HBeAg positive to HBeAb 
positive while receiving chronic hepatitis B treatment with nucleos(t)ide analogues (NA); the 
cumulative rate of he patitis B surface antigen (HBsAg) clearance was also ascertained during 
follow up.  
 
I am seeking some points of clarification from the authors:  
 
1. Abstract: under Methods - I assume that all patients had chronic hepatitis B infection - 
i.e. they were all HBs Ag positive? Perhaps this sentence could be rephrased for clarity?  
 
2. Background: reference is made to discontinuing NAs after ≥12 months of consolidation 
therapy in patients who on treatment. Is this the strategy employed in this patient 
cohort?  Under "a ntiviral therapy" it is stated that all but 12 patients continued on 
antiviral therapy after 12 months of being HBeAg negative - i.e. do all seroconverting 
patients continue NAs indefinitely?  
 
3. Methods: It is unclear how the 203 study patients were selecte d. I assume they were all 
HBsAg positive (not HBsAg negative) to qualify for treatment? What was the study 
period and were all patients who underwent HBeAg seroconversion on treatment 
included (except for those with the stated exclusion criteria)?  
 
4. What  was the loss to follow up and how was that handled?  
 
5. Was there a difference in outcome in patients who had entecavir or tenofovir as first 
line, or as rescue therapy?  
 
6. Statistical analysis: please clarify following sentence: "chi -square and Fisher's e xact 
test were used to compare qualitative variables".  
 
7. The Discussion section needs more structure. For example the first para - some of the 
information needs to be included in Results.  
 
8. The Discussion would benefit from placing these results in the context of available 
literature and emphasizing the contribution made by the study to the body of 
knowledge in this area.  
Are the metho ds 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 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 manus cript or would you recommend an 
additional statistical review?  
If an additional s tatistical review is recommended, please speci fy 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 manuscript:  
 
Accept able 
 
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, f ees, funding, or salary 
from an organisation that may in any way  gain or lose financial ly from the 
publication of this manuscript, either now or in the future?  
 
2.  Do you hold any stocks or shares in an organisation t hat may in any way gain or 
lose financially from the publication of this manuscript, either now or in th e 
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 conte nt 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 understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or 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 Acc ess 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 in cluded 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: Cumulative Incidence of Hepatocellular Carcinoma and Hep atitis B Surface Antigen 
Seroclearance after Nucleos(t)ide analogue -induced Hepatitis B e Antigen Seroclearance  
 
Version: 0 Date: 19 Nov 2019  
 
Reviewer: Monica Robotin  
 
Reviewer's report:  
 
This paper ascertained HCC risk in patients who seroconverted from HBeAg positive to HBeAb 
positive while receiving chronic hepatitis B treatment with nucleos(t)ide analogues (NA); the 
cumulative rate of he patitis B surface antigen (HBsAg) clearance was also ascertained during 
follow up.  
 
I am seeking some points of clarification from the authors:  
 
1. Abstract: under Methods - I assume that all patients had chronic hepatitis B infection - 
i.e. they were all HBs Ag positive? Perhaps this sentence could be rephrased for clarity?  
 
2. Background: reference is made to discontinuing NAs after ≥12 months of consolidation 
therapy in patients who on treatment. Is this the strategy employed in this patient 
cohort?  Under "a ntiviral therapy" it is stated that all but 12 patients continued on 
antiviral therapy after 12 months of being HBeAg negative - i.e. do all seroconverting 
patients continue NAs indefinitely?  
 
3. Methods: It is unclear how the 203 study patients were selecte d. I assume they were all 
HBsAg positive (not HBsAg negative) to qualify for treatment? What was the study 
period and were all patients who underwent HBeAg seroconversion on treatment 
included (except for those with the stated exclusion criteria)?  
 
4. What  was the loss to follow up and how was that handled?  
 
5. Was there a difference in outcome in patients who had entecavir or tenofovir as first 
line, or as rescue therapy?  
 
6. Statistical analysis: please clarify following sentence: "chi -square and Fisher's e xact 
test were used to compare qualitative variables".  
 
7. The Discussion section needs more structure. For example the first para - some of the 
information needs to be included in Results.  
 
8. The Discussion would benefit from placing these results in the context of available 
literature and emphasizing the contribution made by the study to the body of 
knowledge in this area.  
Are the metho ds 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 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 manus cript or would you recommend an 
additional statistical review?  
If an additional s tatistical review is recommended, please speci fy 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 manuscript:  
 
Accept able 
 
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, f ees, funding, or salary 
from an organisation that may in any way  gain or lose financial ly from the 
publication of this manuscript, either now or in the future?  
 
2.  Do you hold any stocks or shares in an organisation t hat may in any way gain or 
lose financially from the publication of this manuscript, either now or in th e 
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 conte nt 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 understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or 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 Acc ess 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 in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
 
assistant