Reviewer ’s report  
 
Title:  The Frequency, Clinical Course, and Health Related Quality of Life in Adults with 
Gilbert's Syndrome: A Longitudinal Study  
 
Version: 0 Date: 19 Sep 2018 
 
Reviewer:  Saeed  Mohammad  
 
Reviewer’s report:  
 
The authors approach Gilbert disease to measure HRQOL. Just as has been said it is often 
ignored as it is considered a benign illness with no long term repercussions. The authors 
demonstrate that this may not be true.  
 
In the inclusion criteria, it is unclear if all those conditions had to be met or just some. Pag e 6, 
lines 41 -56 
 
 
Results:  
 
Please describe how the initial online screening was done? How were participants targeted? 
Were they representative of the general Egyptian population? This is important if the authors 
would like to extrapolate the findings to th e entire Egyptian population  
 
Please split Table 1 up, there is too much information compressed in the table. It also appears 
that the controls may be healthier than the GS patients. None had comorbid conditions or were 
taking medications  
 
Page 13  
 
Subheading comorbidities: The authors report that the rate of comorbidities is similar to that of 
the general population but no evidence is given. Same is the result for celiac disease and food 
intolerance  
 
HRQOL.  
 
Although the authors report that HRQOl was  lower in GS patients when they were jaundiced, it 
seems that the assessment was done at one point in time. Meaning they were asked how they felt 
when they were jaundiced and not jaundiced and could be subject to recall bias.  
 
 
Conclusions:  
 
It is well known  that stressors will exacerbate the underlying hyperbilirubinemia in patients with 
GS. Therefore fasting, low calorie diet, pregnancy and surgery are expected to cause this. 
Vitamin D levels may also be expected to be lower in these patients as they have h igher bilirubin 
at baseline, however the difference from the general population is significant. This seems to the 
main take away from the study  
 
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 
assessme nt in your comments to the editors.  
 
Not relevant to this manuscript  
 
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 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 now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the c ontent 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 a ny 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 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 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:  The Frequency, Clinical Course, and Health Related Quality of Life in Adults with 
Gilbert's Syndrome: A Longitudinal Study  
 
Version: 0 Date: 19 Sep 2018 
 
Reviewer:  Saeed  Mohammad  
 
Reviewer’s report:  
 
The authors approach Gilbert disease to measure HRQOL. Just as has been said it is often 
ignored as it is considered a benign illness with no long term repercussions. The authors 
demonstrate that this may not be true.  
 
In the inclusion criteria, it is unclear if all those conditions had to be met or just some. Pag e 6, 
lines 41 -56 
 
 
Results:  
 
Please describe how the initial online screening was done? How were participants targeted? 
Were they representative of the general Egyptian population? This is important if the authors 
would like to extrapolate the findings to th e entire Egyptian population  
 
Please split Table 1 up, there is too much information compressed in the table. It also appears 
that the controls may be healthier than the GS patients. None had comorbid conditions or were 
taking medications  
 
Page 13  
 
Subheading comorbidities: The authors report that the rate of comorbidities is similar to that of 
the general population but no evidence is given. Same is the result for celiac disease and food 
intolerance  
 
HRQOL.  
 
Although the authors report that HRQOl was  lower in GS patients when they were jaundiced, it 
seems that the assessment was done at one point in time. Meaning they were asked how they felt 
when they were jaundiced and not jaundiced and could be subject to recall bias.  
 
 
Conclusions:  
 
It is well known  that stressors will exacerbate the underlying hyperbilirubinemia in patients with 
GS. Therefore fasting, low calorie diet, pregnancy and surgery are expected to cause this. 
Vitamin D levels may also be expected to be lower in these patients as they have h igher bilirubin 
at baseline, however the difference from the general population is significant. This seems to the 
main take away from the study  
 
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 
assessme nt in your comments to the editors.  
 
Not relevant to this manuscript  
 
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 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 now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the c ontent 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 a ny 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 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 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:  The Frequency, Clinical Course, and Health Related Quality of Life in Adults with 
Gilbert's Syndrome: A Longitudinal Study  
 
Version: 0 Date: 19 Sep 2018 
 
Reviewer:  Saeed  Mohammad  
 
Reviewer’s report:  
 
The authors approach Gilbert disease to measure HRQOL. Just as has been said it is often 
ignored as it is considered a benign illness with no long term repercussions. The authors 
demonstrate that this may not be true.  
 
In the inclusion criteria, it is unclear if all those conditions had to be met or just some. Pag e 6, 
lines 41 -56 
 
 
Results:  
 
Please describe how the initial online screening was done? How were participants targeted? 
Were they representative of the general Egyptian population? This is important if the authors 
would like to extrapolate the findings to th e entire Egyptian population  
 
Please split Table 1 up, there is too much information compressed in the table. It also appears 
that the controls may be healthier than the GS patients. None had comorbid conditions or were 
taking medications  
 
Page 13  
 
Subheading comorbidities: The authors report that the rate of comorbidities is similar to that of 
the general population but no evidence is given. Same is the result for celiac disease and food 
intolerance  
 
HRQOL.  
 
Although the authors report that HRQOl was  lower in GS patients when they were jaundiced, it 
seems that the assessment was done at one point in time. Meaning they were asked how they felt 
when they were jaundiced and not jaundiced and could be subject to recall bias.  
 
 
Conclusions:  
 
It is well known  that stressors will exacerbate the underlying hyperbilirubinemia in patients with 
GS. Therefore fasting, low calorie diet, pregnancy and surgery are expected to cause this. 
Vitamin D levels may also be expected to be lower in these patients as they have h igher bilirubin 
at baseline, however the difference from the general population is significant. This seems to the 
main take away from the study  
 
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 
assessme nt in your comments to the editors.  
 
Not relevant to this manuscript  
 
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 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 now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the c ontent 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 a ny 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 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 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