Reviewer’s report  
 
Title: Plasma Lipidome, PNPLA3 polymorphism and hepatic steatosis in hereditary 
hemochromatosis  
 
Version: 0 Date: 31 Jan 2020  
 
Reviewer: Giuliano Ramadori  
 
Reviewer's report:  
 
Authors report  on a retrospective study performed on 54 patients (72% male) who had been 
diagnosed hereditary hemochromatosis(HH) based on laboratory findings,ferriitin -,iron-
,transferrin -serum level and transferrin saturation and on HFE C282Y -homozigoty.  
 
Seum lipids wi th the addition of polar lipids and PNPLA3 -polymorphism were also 
investigated.One serum sample, on a routine follow -up examination from each patient was 
investigated.Anamnestic information about tolerated alcoholic beverages consumption was 
under 20 gramm  alcohol per day. The same measurements were performed in 20 healthy 
control persons.Abdominal ultrasonography was also performed in HH -patients and in 
control subjects.  
 
It was found that HH -patients had more frequently hepatic steatosis but liver stiffness was 
quite normal.  
 
HH-patients had higher serum level of tryglicerides but the difference was not significant.  
HH-patients had lower serum phosphatidylcholine(PC) and hig her 
phosphatidilethanolamine.PNLPA3 -polymorphism -study did not reveal any correlation with 
iron and lipid -parameters.  
 
Comment:  
diagnosis of HH is very difficult as it is difficult to learn how high is the daly intake of 
alcoholic beverages.  For this reason further control groups are necessary to drow any 
conclusion.  For these reason it is interesting to read the paper published by Sanchez -Luna SA 
in Hepatol Commun 2017,1:453 -459. 
 
It would have been interesting to follow those patients under absolute restricti on of alcohol 
consumtion.  
 
As no tissue iron -measurement has been performed most of the discussion is mere 
speculation.  It is also important to reed the review published by Bloomer SA in Int J of Mol 
sc.209 ;20:2132.  It is infact not clear whether iron accumu lation alone may be responsible for 
tissue damage.  Cofactors have to be taken into account  
 
 
 
 
 
 
 
Are the methods appropriate an d 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.  
 
No 
 
Are the conclusions drawn a dequately 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 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 manuscr ipt: 
 
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 n ow 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 t o 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 int erests' 
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 m anuscript 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 review policy of the journal  
Reviewer’s report  
 
Title: Plasma Lipidome, PNPLA3 polymorphism and hepatic steatosis in hereditary 
hemochromatosis  
 
Version: 0 Date: 31 Jan 2020  
 
Reviewer: Giuliano Ramadori  
 
Reviewer's report:  
 
Authors report  on a retrospective study performed on 54 patients (72% male) who had been 
diagnosed hereditary hemochromatosis(HH) based on laboratory findings,ferriitin -,iron-
,transferrin -serum level and transferrin saturation and on HFE C282Y -homozigoty.  
 
Seum lipids wi th the addition of polar lipids and PNPLA3 -polymorphism were also 
investigated.One serum sample, on a routine follow -up examination from each patient was 
investigated.Anamnestic information about tolerated alcoholic beverages consumption was 
under 20 gramm  alcohol per day. The same measurements were performed in 20 healthy 
control persons.Abdominal ultrasonography was also performed in HH -patients and in 
control subjects.  
 
It was found that HH -patients had more frequently hepatic steatosis but liver stiffness was 
quite normal.  
 
HH-patients had higher serum level of tryglicerides but the difference was not significant.  
HH-patients had lower serum phosphatidylcholine(PC) and hig her 
phosphatidilethanolamine.PNLPA3 -polymorphism -study did not reveal any correlation with 
iron and lipid -parameters.  
 
Comment:  
diagnosis of HH is very difficult as it is difficult to learn how high is the daly intake of 
alcoholic beverages.  For this reason further control groups are necessary to drow any 
conclusion.  For these reason it is interesting to read the paper published by Sanchez -Luna SA 
in Hepatol Commun 2017,1:453 -459. 
 
It would have been interesting to follow those patients under absolute restricti on of alcohol 
consumtion.  
 
As no tissue iron -measurement has been performed most of the discussion is mere 
speculation.  It is also important to reed the review published by Bloomer SA in Int J of Mol 
sc.209 ;20:2132.  It is infact not clear whether iron accumu lation alone may be responsible for 
tissue damage.  Cofactors have to be taken into account  
 
 
 
 
 
 
 
Are the methods appropriate an d 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.  
 
No 
 
Are the conclusions drawn a dequately 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 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 manuscr ipt: 
 
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 n ow 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 t o 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 int erests' 
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 m anuscript 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 review policy of the journal  
Please review this paper.
user
Reviewer’s report  
 
Title: Plasma Lipidome, PNPLA3 polymorphism and hepatic steatosis in hereditary 
hemochromatosis  
 
Version: 0 Date: 31 Jan 2020  
 
Reviewer: Giuliano Ramadori  
 
Reviewer's report:  
 
Authors report  on a retrospective study performed on 54 patients (72% male) who had been 
diagnosed hereditary hemochromatosis(HH) based on laboratory findings,ferriitin -,iron-
,transferrin -serum level and transferrin saturation and on HFE C282Y -homozigoty.  
 
Seum lipids wi th the addition of polar lipids and PNPLA3 -polymorphism were also 
investigated.One serum sample, on a routine follow -up examination from each patient was 
investigated.Anamnestic information about tolerated alcoholic beverages consumption was 
under 20 gramm  alcohol per day. The same measurements were performed in 20 healthy 
control persons.Abdominal ultrasonography was also performed in HH -patients and in 
control subjects.  
 
It was found that HH -patients had more frequently hepatic steatosis but liver stiffness was 
quite normal.  
 
HH-patients had higher serum level of tryglicerides but the difference was not significant.  
HH-patients had lower serum phosphatidylcholine(PC) and hig her 
phosphatidilethanolamine.PNLPA3 -polymorphism -study did not reveal any correlation with 
iron and lipid -parameters.  
 
Comment:  
diagnosis of HH is very difficult as it is difficult to learn how high is the daly intake of 
alcoholic beverages.  For this reason further control groups are necessary to drow any 
conclusion.  For these reason it is interesting to read the paper published by Sanchez -Luna SA 
in Hepatol Commun 2017,1:453 -459. 
 
It would have been interesting to follow those patients under absolute restricti on of alcohol 
consumtion.  
 
As no tissue iron -measurement has been performed most of the discussion is mere 
speculation.  It is also important to reed the review published by Bloomer SA in Int J of Mol 
sc.209 ;20:2132.  It is infact not clear whether iron accumu lation alone may be responsible for 
tissue damage.  Cofactors have to be taken into account  
 
 
 
 
 
 
 
Are the methods appropriate an d 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.  
 
No 
 
Are the conclusions drawn a dequately 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 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 manuscr ipt: 
 
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 n ow 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 t o 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 int erests' 
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 m anuscript 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 review policy of the journal  
assistant