Reviewer ’s report  
 
Title: Changes in Plasma Ghrelin and Leptin Levels in Patients with Pe ptic Ulcer and Gastritis  
following Eradication of Helicobacter Pylori Infection  
 
Version: 0 Date: 25 May 2016  
 
Reviewer: Simona Cardaropoli  
 
Reviewer's report:  
 
The Authors observed lower plasma ghrelin levels in Helicobacter pylori positive patient s than in 
controls, while plasma leptin levels did not change. In all patients, decreased desacyl -ghrelin 
levels were found after 12 weeks of successful H.pylori eradication while, only in patients with 
peptic ulcer, higher leptin levels were found both af ter unsuccessful and after successful H.pylori 
eradication. Furthermore, the investigators observed a negative (but not significant) correlation 
between active ghrelin levels and atrophic pattern in peptic ulcer patients.  
 
 
 
MAJOR REVISIONS  
 
* Please give some information about total -, active - and  desacyl -ghrelin in the Introduction and 
provide a comment on these molecules in the Discussion. Why sometimes you showed total and 
active ghrelin results (Figure 1) and sometimes active and desacyl - ghrelin results (Figure 2)?  
 
 
* Table 1 is incomplete and poorly described in the text: a) Some of controls characteristics are 
absent (e.g.  alcohol intake, smoking, laboratory data; b) Why did you choose those Laboratory 
data?; c) Please better explain th e meaning of the parameter "HbA1c (JDS; %)"  
 
 
* In the Discussion section , it would be useful to try to explain why your results differ from 
other studies (for example, the use of different tests for the diagnosis of H.pylori positivity, a 
longer or shorter  period between the eradication and the next dosage of the molecules, the 
eventual presence and degree of gastric mucosal lesions, age and gender of the subjects of study, 
etc.).  
 
 
* The interpretation of your results is unclear. You justify the decrease in ghrelin levels with the 
destruction of gastric cells, in all patients. This decrease is milder in the group with peptic ulcer, 
since this disease is characterized by oxidative stress which leads to an increased production of 
ghrelin. Furthermore, you repor ted that eradication leads to a further reduction in ghrelin levels, 
since oxidative stress is reduced with treatment, but mucosal lesions are still present. If I 
understand your interpretation, we can assume that after a longer time from eradication, ghre lin 
levels could return to control levels or higher. It would be interesting to know the plasma levels 
of ghrelin and leptin after at least 6 -12 months after eradication of H. pylori!  
 
 
* Most of your results are a confirmation of previous studies. I suggest  you emphasize the 
strengths of your work and to point out what your study adds to the findings of the past 
publications.  
 
 
 
 
MINOR REVISIONS  
 
* In the first page, in Title (line 5), Running title (line 55) and Keywords (line 58), please change 
"Pylori" with "p ylori".  
 
 
* Which statistical analysis did you use to evaluate correlation? (page 9, line 5)  
 
 
* In Figure 1A, you indicated a significant difference between Peptic ulcer and Gastritis groups, 
but this is not so clear in the graphic. Furthermore you did not co mment this result in the text.  
 
 
* In Figures 5A, B e C, please change "Artophic pattern" with "Atrophic pattern".  
 
 
 
 
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.  
 
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 manuscript:  
 
Acceptable  
 
 
 
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five y ears 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 i n 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, fund ing, 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 interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be incl uded  
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 authors'  
responses. I agree for my report to be made available under a n Ope n 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: Changes in Plasma Ghrelin and Leptin Levels in Patients with Pe ptic Ulcer and Gastritis  
following Eradication of Helicobacter Pylori Infection  
 
Version: 0 Date: 25 May 2016  
 
Reviewer: Simona Cardaropoli  
 
Reviewer's report:  
 
The Authors observed lower plasma ghrelin levels in Helicobacter pylori positive patient s than in 
controls, while plasma leptin levels did not change. In all patients, decreased desacyl -ghrelin 
levels were found after 12 weeks of successful H.pylori eradication while, only in patients with 
peptic ulcer, higher leptin levels were found both af ter unsuccessful and after successful H.pylori 
eradication. Furthermore, the investigators observed a negative (but not significant) correlation 
between active ghrelin levels and atrophic pattern in peptic ulcer patients.  
 
 
 
MAJOR REVISIONS  
 
* Please give some information about total -, active - and  desacyl -ghrelin in the Introduction and 
provide a comment on these molecules in the Discussion. Why sometimes you showed total and 
active ghrelin results (Figure 1) and sometimes active and desacyl - ghrelin results (Figure 2)?  
 
 
* Table 1 is incomplete and poorly described in the text: a) Some of controls characteristics are 
absent (e.g.  alcohol intake, smoking, laboratory data; b) Why did you choose those Laboratory 
data?; c) Please better explain th e meaning of the parameter "HbA1c (JDS; %)"  
 
 
* In the Discussion section , it would be useful to try to explain why your results differ from 
other studies (for example, the use of different tests for the diagnosis of H.pylori positivity, a 
longer or shorter  period between the eradication and the next dosage of the molecules, the 
eventual presence and degree of gastric mucosal lesions, age and gender of the subjects of study, 
etc.).  
 
 
* The interpretation of your results is unclear. You justify the decrease in ghrelin levels with the 
destruction of gastric cells, in all patients. This decrease is milder in the group with peptic ulcer, 
since this disease is characterized by oxidative stress which leads to an increased production of 
ghrelin. Furthermore, you repor ted that eradication leads to a further reduction in ghrelin levels, 
since oxidative stress is reduced with treatment, but mucosal lesions are still present. If I 
understand your interpretation, we can assume that after a longer time from eradication, ghre lin 
levels could return to control levels or higher. It would be interesting to know the plasma levels 
of ghrelin and leptin after at least 6 -12 months after eradication of H. pylori!  
 
 
* Most of your results are a confirmation of previous studies. I suggest  you emphasize the 
strengths of your work and to point out what your study adds to the findings of the past 
publications.  
 
 
 
 
MINOR REVISIONS  
 
* In the first page, in Title (line 5), Running title (line 55) and Keywords (line 58), please change 
"Pylori" with "p ylori".  
 
 
* Which statistical analysis did you use to evaluate correlation? (page 9, line 5)  
 
 
* In Figure 1A, you indicated a significant difference between Peptic ulcer and Gastritis groups, 
but this is not so clear in the graphic. Furthermore you did not co mment this result in the text.  
 
 
* In Figures 5A, B e C, please change "Artophic pattern" with "Atrophic pattern".  
 
 
 
 
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.  
 
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 manuscript:  
 
Acceptable  
 
 
 
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five y ears 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 i n 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, fund ing, 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 interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be incl uded  
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 authors'  
responses. I agree for my report to be made available under a n Ope n 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: Changes in Plasma Ghrelin and Leptin Levels in Patients with Pe ptic Ulcer and Gastritis  
following Eradication of Helicobacter Pylori Infection  
 
Version: 0 Date: 25 May 2016  
 
Reviewer: Simona Cardaropoli  
 
Reviewer's report:  
 
The Authors observed lower plasma ghrelin levels in Helicobacter pylori positive patient s than in 
controls, while plasma leptin levels did not change. In all patients, decreased desacyl -ghrelin 
levels were found after 12 weeks of successful H.pylori eradication while, only in patients with 
peptic ulcer, higher leptin levels were found both af ter unsuccessful and after successful H.pylori 
eradication. Furthermore, the investigators observed a negative (but not significant) correlation 
between active ghrelin levels and atrophic pattern in peptic ulcer patients.  
 
 
 
MAJOR REVISIONS  
 
* Please give some information about total -, active - and  desacyl -ghrelin in the Introduction and 
provide a comment on these molecules in the Discussion. Why sometimes you showed total and 
active ghrelin results (Figure 1) and sometimes active and desacyl - ghrelin results (Figure 2)?  
 
 
* Table 1 is incomplete and poorly described in the text: a) Some of controls characteristics are 
absent (e.g.  alcohol intake, smoking, laboratory data; b) Why did you choose those Laboratory 
data?; c) Please better explain th e meaning of the parameter "HbA1c (JDS; %)"  
 
 
* In the Discussion section , it would be useful to try to explain why your results differ from 
other studies (for example, the use of different tests for the diagnosis of H.pylori positivity, a 
longer or shorter  period between the eradication and the next dosage of the molecules, the 
eventual presence and degree of gastric mucosal lesions, age and gender of the subjects of study, 
etc.).  
 
 
* The interpretation of your results is unclear. You justify the decrease in ghrelin levels with the 
destruction of gastric cells, in all patients. This decrease is milder in the group with peptic ulcer, 
since this disease is characterized by oxidative stress which leads to an increased production of 
ghrelin. Furthermore, you repor ted that eradication leads to a further reduction in ghrelin levels, 
since oxidative stress is reduced with treatment, but mucosal lesions are still present. If I 
understand your interpretation, we can assume that after a longer time from eradication, ghre lin 
levels could return to control levels or higher. It would be interesting to know the plasma levels 
of ghrelin and leptin after at least 6 -12 months after eradication of H. pylori!  
 
 
* Most of your results are a confirmation of previous studies. I suggest  you emphasize the 
strengths of your work and to point out what your study adds to the findings of the past 
publications.  
 
 
 
 
MINOR REVISIONS  
 
* In the first page, in Title (line 5), Running title (line 55) and Keywords (line 58), please change 
"Pylori" with "p ylori".  
 
 
* Which statistical analysis did you use to evaluate correlation? (page 9, line 5)  
 
 
* In Figure 1A, you indicated a significant difference between Peptic ulcer and Gastritis groups, 
but this is not so clear in the graphic. Furthermore you did not co mment this result in the text.  
 
 
* In Figures 5A, B e C, please change "Artophic pattern" with "Atrophic pattern".  
 
 
 
 
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.  
 
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 manuscript:  
 
Acceptable  
 
 
 
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five y ears 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 i n 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, fund ing, 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 interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be incl uded  
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 authors'  
responses. I agree for my report to be made available under a n Ope n 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