Reviewer ’s report  
 
Title: Comprehensive evaluation of effects and safety of statin on the progression of liver 
cirrhosis: a systematic review and meta -analysis  
 
Version: 1 Date: 16 Oct 2019  
 
Reviewer: Yee Hui Yeo  
 
Reviewer's report:  
 
The author demonstrated the potential of  statin in lowering the risk of the occurrence of 
decompensated liver cirrhosis, HCC and mortality. This is a well done study with high clinical 
relevance and public health impact. However, there are several points that warrant attention:  
1. Recent study h as showed the difference in the risk of HCC and mortality between 
lipophilic and hydrophilic statin. The authors should perform a subgroup analysis regarding this.  
2. (Ann Intern Med. 2019 Sep 3;171(5):318 -327. doi: 10.7326/M18 -2753. Epub 2019 
Aug 20. Lipo philic Statins and Risk for Hepatocellular Carcinoma and Death in Patients With 
Chronic Viral Hepatitis: Results From a Nationwide Swedish Population. Simon TG1, Duberg 
AS2, Aleman S3, Hagstrom H4, Nguyen LH1, Khalili H5, Chung RT1, Ludvigsson JF6.)  
3. Dose dependent effects on the complications of statin should be performed to identify a 
dose that is beneficial but not harmful to the patients  
4. For best practice, the author MUST provide index of heterogeneity in result section. 
Severe heterogeneity should  be mentioned in the abstract, conclusion section.  
5. Quality assessment results were not presented  
6. If severe heterogeneity is presented (which is understandably high in meta -analysis of 
cohort studies), random effects model should be use instead of fix ed effects model  
7. Visceral should be variceal  
 
Minor  
1. abstract: improved survival rate (HR = 0.782, 95% CI: 0.718 - 0.846) should be changed into 
"decreased mortality rate (HR = 0.782, 95% CI: 0.718 - 0.846)" or "improved survival rate (HR 
of mortalit y = 0.782, 95% CI: 0.718 - 0.846)"  
2. hepatic cell carcinoma should be changed into hepatocellular carcinoma  
 
 
 
 
 
 
 
 
 
Are the methods 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.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an addition al 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 ga in 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 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 al l 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 pee r 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 autho rs' 
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 include d 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: Comprehensive evaluation of effects and safety of statin on the progression of liver 
cirrhosis: a systematic review and meta -analysis  
 
Version: 1 Date: 16 Oct 2019  
 
Reviewer: Yee Hui Yeo  
 
Reviewer's report:  
 
The author demonstrated the potential of  statin in lowering the risk of the occurrence of 
decompensated liver cirrhosis, HCC and mortality. This is a well done study with high clinical 
relevance and public health impact. However, there are several points that warrant attention:  
1. Recent study h as showed the difference in the risk of HCC and mortality between 
lipophilic and hydrophilic statin. The authors should perform a subgroup analysis regarding this.  
2. (Ann Intern Med. 2019 Sep 3;171(5):318 -327. doi: 10.7326/M18 -2753. Epub 2019 
Aug 20. Lipo philic Statins and Risk for Hepatocellular Carcinoma and Death in Patients With 
Chronic Viral Hepatitis: Results From a Nationwide Swedish Population. Simon TG1, Duberg 
AS2, Aleman S3, Hagstrom H4, Nguyen LH1, Khalili H5, Chung RT1, Ludvigsson JF6.)  
3. Dose dependent effects on the complications of statin should be performed to identify a 
dose that is beneficial but not harmful to the patients  
4. For best practice, the author MUST provide index of heterogeneity in result section. 
Severe heterogeneity should  be mentioned in the abstract, conclusion section.  
5. Quality assessment results were not presented  
6. If severe heterogeneity is presented (which is understandably high in meta -analysis of 
cohort studies), random effects model should be use instead of fix ed effects model  
7. Visceral should be variceal  
 
Minor  
1. abstract: improved survival rate (HR = 0.782, 95% CI: 0.718 - 0.846) should be changed into 
"decreased mortality rate (HR = 0.782, 95% CI: 0.718 - 0.846)" or "improved survival rate (HR 
of mortalit y = 0.782, 95% CI: 0.718 - 0.846)"  
2. hepatic cell carcinoma should be changed into hepatocellular carcinoma  
 
 
 
 
 
 
 
 
 
Are the methods 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.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an addition al 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 ga in 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 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 al l 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 pee r 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 autho rs' 
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 include d 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: Comprehensive evaluation of effects and safety of statin on the progression of liver 
cirrhosis: a systematic review and meta -analysis  
 
Version: 1 Date: 16 Oct 2019  
 
Reviewer: Yee Hui Yeo  
 
Reviewer's report:  
 
The author demonstrated the potential of  statin in lowering the risk of the occurrence of 
decompensated liver cirrhosis, HCC and mortality. This is a well done study with high clinical 
relevance and public health impact. However, there are several points that warrant attention:  
1. Recent study h as showed the difference in the risk of HCC and mortality between 
lipophilic and hydrophilic statin. The authors should perform a subgroup analysis regarding this.  
2. (Ann Intern Med. 2019 Sep 3;171(5):318 -327. doi: 10.7326/M18 -2753. Epub 2019 
Aug 20. Lipo philic Statins and Risk for Hepatocellular Carcinoma and Death in Patients With 
Chronic Viral Hepatitis: Results From a Nationwide Swedish Population. Simon TG1, Duberg 
AS2, Aleman S3, Hagstrom H4, Nguyen LH1, Khalili H5, Chung RT1, Ludvigsson JF6.)  
3. Dose dependent effects on the complications of statin should be performed to identify a 
dose that is beneficial but not harmful to the patients  
4. For best practice, the author MUST provide index of heterogeneity in result section. 
Severe heterogeneity should  be mentioned in the abstract, conclusion section.  
5. Quality assessment results were not presented  
6. If severe heterogeneity is presented (which is understandably high in meta -analysis of 
cohort studies), random effects model should be use instead of fix ed effects model  
7. Visceral should be variceal  
 
Minor  
1. abstract: improved survival rate (HR = 0.782, 95% CI: 0.718 - 0.846) should be changed into 
"decreased mortality rate (HR = 0.782, 95% CI: 0.718 - 0.846)" or "improved survival rate (HR 
of mortalit y = 0.782, 95% CI: 0.718 - 0.846)"  
2. hepatic cell carcinoma should be changed into hepatocellular carcinoma  
 
 
 
 
 
 
 
 
 
Are the methods 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.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an addition al 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 ga in 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 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 al l 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 pee r 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 autho rs' 
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 include d as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant