Reviewer’ s report
Title: The Clinical Efficacy and Adverse Effects of Entecavir plus Thymosin alpha-1 Combination
Therapy versus Entecavir Monotherapy in HBV-related Cirrhosis: A Systematic Review andMeta-analysis
Version: 0Date: 04 Apr 2020
Reviewer: Hie-Won Hann
Reviewer's report:
April 4, 2020
Review for the article entitled "The Clinical Efficacy and Adverse Effects of Entecavir plusThymosin alpha-1 Combination Therapy versus Entecavir Monotherapy in HBV-related Cirrhosis:A Systemic Review and Meta-analysis".General CommentWhile the favorable anti-HBV effect of Tα1 has been reported in the past, there have beencontroversies as to the benefit of combining Tα1 with Entecavir over Entecavir alone. In thismanuscript, the authors undertook a commendable systematic world literature search. They nowpresented their systematic review and meta-analysis of the seven RCTs that included 1144patients. The patients were all Chinese.They documented the superiority of the combination therapy over Entecavir alone with regard tothe achievement of HBV DNA undetectable rate, HBeAg loss, improvement of biochemicalparameters and the several markers of hepatic fibrosis (this last only from one study).Overall, from the authors' systemic review and meta-analysis, the combination therapy ofEntecavir with Tα1 appears far beneficial for CHB patients in particular those with cirrhosis.
Questions and suggestions.
1. Need attention to some typos and grammartical errors.2. Result: P. 6, line 3, (DHBC) should be CHBC for compensated HBV-related cirrhosis3. P. 7, with regard to the HBV DNA loss (undetectable rate), two subgroups were studied,
Subgroup 1 for only at 24 weeks and subgroup 2 for more than 24 weeks up to 48 and 52
weeks.
Results
At 24 Weeks. HBV DNA loss was better in ETV+ Tα1 combination group.Question. Is this result from the subgroup 1 only?There was no difference in the HBV DNA loss at 32 and 52 weeksQuestion. This must be from Subgroup 2.
Where is the result of HBV DNA loss at 24 weeks for this subgroup 2?
Also could you hypothesize the reason for no advantage of combination therapy after
24 weeks?
4. P. 9, line 23, …….significantly enhanced by treatment….. confusing.
Authors must mean the improvement of these serum markers for hepatic fibrosis by
treatment.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
YesDoes 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.
YesAre 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 furtherassessment in your comments to the editors.
I am able to assess the statisticsQuality 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 thismanuscript, 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 your reply is yes to any, please give details below.
I declare that I have no competing interest.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 reportincluding 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 commentsto the editors, which will not be published.
I agree to the open peer review policy of the journal
Reviewer’ s report
Title: The Clinical Efficacy and Adverse Effects of Entecavir plus Thymosin alpha-1 Combination
Therapy versus Entecavir Monotherapy in HBV-related Cirrhosis: A Systematic Review andMeta-analysis
Version: 0Date: 04 Apr 2020
Reviewer: Hie-Won Hann
Reviewer's report:
April 4, 2020
Review for the article entitled "The Clinical Efficacy and Adverse Effects of Entecavir plusThymosin alpha-1 Combination Therapy versus Entecavir Monotherapy in HBV-related Cirrhosis:A Systemic Review and Meta-analysis".General CommentWhile the favorable anti-HBV effect of Tα1 has been reported in the past, there have beencontroversies as to the benefit of combining Tα1 with Entecavir over Entecavir alone. In thismanuscript, the authors undertook a commendable systematic world literature search. They nowpresented their systematic review and meta-analysis of the seven RCTs that included 1144patients. The patients were all Chinese.They documented the superiority of the combination therapy over Entecavir alone with regard tothe achievement of HBV DNA undetectable rate, HBeAg loss, improvement of biochemicalparameters and the several markers of hepatic fibrosis (this last only from one study).Overall, from the authors' systemic review and meta-analysis, the combination therapy ofEntecavir with Tα1 appears far beneficial for CHB patients in particular those with cirrhosis.
Questions and suggestions.
1. Need attention to some typos and grammartical errors.2. Result: P. 6, line 3, (DHBC) should be CHBC for compensated HBV-related cirrhosis3. P. 7, with regard to the HBV DNA loss (undetectable rate), two subgroups were studied,
Subgroup 1 for only at 24 weeks and subgroup 2 for more than 24 weeks up to 48 and 52
weeks.
Results
At 24 Weeks. HBV DNA loss was better in ETV+ Tα1 combination group.Question. Is this result from the subgroup 1 only?There was no difference in the HBV DNA loss at 32 and 52 weeksQuestion. This must be from Subgroup 2.
Where is the result of HBV DNA loss at 24 weeks for this subgroup 2?
Also could you hypothesize the reason for no advantage of combination therapy after
24 weeks?
4. P. 9, line 23, …….significantly enhanced by treatment….. confusing.
Authors must mean the improvement of these serum markers for hepatic fibrosis by
treatment.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
YesDoes 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.
YesAre 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 furtherassessment in your comments to the editors.
I am able to assess the statisticsQuality 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 thismanuscript, 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 your reply is yes to any, please give details below.
I declare that I have no competing interest.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 reportincluding 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 commentsto 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: The Clinical Efficacy and Adverse Effects of Entecavir plus Thymosin alpha-1 Combination
Therapy versus Entecavir Monotherapy in HBV-related Cirrhosis: A Systematic Review andMeta-analysis
Version: 0Date: 04 Apr 2020
Reviewer: Hie-Won Hann
Reviewer's report:
April 4, 2020
Review for the article entitled "The Clinical Efficacy and Adverse Effects of Entecavir plusThymosin alpha-1 Combination Therapy versus Entecavir Monotherapy in HBV-related Cirrhosis:A Systemic Review and Meta-analysis".General CommentWhile the favorable anti-HBV effect of Tα1 has been reported in the past, there have beencontroversies as to the benefit of combining Tα1 with Entecavir over Entecavir alone. In thismanuscript, the authors undertook a commendable systematic world literature search. They nowpresented their systematic review and meta-analysis of the seven RCTs that included 1144patients. The patients were all Chinese.They documented the superiority of the combination therapy over Entecavir alone with regard tothe achievement of HBV DNA undetectable rate, HBeAg loss, improvement of biochemicalparameters and the several markers of hepatic fibrosis (this last only from one study).Overall, from the authors' systemic review and meta-analysis, the combination therapy ofEntecavir with Tα1 appears far beneficial for CHB patients in particular those with cirrhosis.
Questions and suggestions.
1. Need attention to some typos and grammartical errors.2. Result: P. 6, line 3, (DHBC) should be CHBC for compensated HBV-related cirrhosis3. P. 7, with regard to the HBV DNA loss (undetectable rate), two subgroups were studied,
Subgroup 1 for only at 24 weeks and subgroup 2 for more than 24 weeks up to 48 and 52
weeks.
Results
At 24 Weeks. HBV DNA loss was better in ETV+ Tα1 combination group.Question. Is this result from the subgroup 1 only?There was no difference in the HBV DNA loss at 32 and 52 weeksQuestion. This must be from Subgroup 2.
Where is the result of HBV DNA loss at 24 weeks for this subgroup 2?
Also could you hypothesize the reason for no advantage of combination therapy after
24 weeks?
4. P. 9, line 23, …….significantly enhanced by treatment….. confusing.
Authors must mean the improvement of these serum markers for hepatic fibrosis by
treatment.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
YesDoes 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.
YesAre 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 furtherassessment in your comments to the editors.
I am able to assess the statisticsQuality 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 thismanuscript, 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 your reply is yes to any, please give details below.
I declare that I have no competing interest.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 reportincluding 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 commentsto the editors, which will not be published.
I agree to the open peer review policy of the journal
assistant