Reviewer’s report 
Title:  The prevalence of functional dyspepsia using Rome III questionnaire among chronic 
hepatitis C patients. 
 
Version:  0 Date:  29 Oct 2015 
 
Reviewer:  Benjamin Misselwitz 
 
Reviewer's report: 
The study by Mohamed et al deals with the interesti ng question of extrahepatic manifestations of 
Hepatitis C. The authors identify functional dyspep sia (FD) as a frequent complaint in HCV 
infected patients; liver fibrosis seems to increase  the risk of FD further. These are new and 
relevant findings. As detailed below, the manuscrip ts suffers several shortcomings which should 
be addressed. 
 
Major comments 
- Control group. Obviously case control studies cri tically depend on a valid control group. The 
authors should report, how the control group was re cruited. It remains a limitation of the 
study that cases and controls were not recruited in  an identical way (and the authors should 
mention this as a limitation) 
- Considering the high prevalence of hepatitis C in  Egypt (15-20%?) were the healthy 
volunteers tested for HCV infection? If yes, how ma ny positive cases were found? Was 
dyspepsia also more frequent in the group of "healt hy volunteers with HCV infection"  
- Results: the statement that there was "no differe nce in the demographics" between control and 
cases (first page of results, 2nd paragraph) is a g ross misrepresentation of the data 
considering highly significant differences in age, sex, smoking, BMI 
- Discussion: one additional obvious explanation of  the observation of the authors would be 
that HCV infection causes (subclinical) depression and thus in turn increases visceral 
sensitivity and the risk for FD.  
- For an analysis as in table 4 typically a univari ate analysis is provided first. This is followed 
by a multivariate analysis for which usually non-si gnificant values are eliminated. This table 
might be a univariate analysis (and Prism 4, to the  best of my knowledge does not support 
true multivariate analysis). The authors should exp lain: Has a different program been used? 
Perhaps the authors might want to consult a statist ician. 
- Style: there are some mistakes in spelling/ gramm ar, some sentences are incomplete (for 
instance line 16 of the 2nd page of the introductio n). The manuscript should be edited by a 
native speaker (this is an urgent request) 
 
Minor points 
- Abbreviation PDS is not defined in the abstract 
- In the Methods section the authors should not pre sent the case report form of their study, 
rather the data collected should be described verba lly (or if appropriate in a table) 
- In Table 4 it should be better defined what the O R refer to: age (above or below a certain 
age?), sex (is female or male sex non-significantly  protective?), BMI (above or below a 
certain BMI?), normal or elevated ALT? 
 
Additional comment: I do not recall a single case o f a hepatitis C patient with dyspepsia (in >5 
years of clinical practice in a European tertiary c are center with a strong Hepatology unit serving 
mainly Caucasian patients); however, in my experien ce depression, dysphoria, fatigue or 
arthralgia are frequent complaints. And (as the aut hors correctly point out) dyspepsia in HCV 
infection has not been described before. This is of  course not meant to question the importance 
or validity of the results of this study. However, the discrepancy points to two interesting 
explanations: the genotype of HCV (mainly 4 in Egyp t but 1 in Europe) and/ or different 
perception of extrahepatic manifestations of HCV in  the Egyptian vs. the European/ American 
culture. It would be interesting to learn the thoug hts of the authors about this. 
 
Are the methods appropriate and well described? 
If not, please specify what is required in your com ments to the authors. 
No 
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 t he data shown? 
If not, please explain in your comments to the auth ors. 
Yes 
Are you able to assess any statistics in the manusc ript 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 manu script: 
Not suitable for publication unless extensively edi ted 
Declaration of competing interests 
Please complete a declaration of competing interest s, considering the following questions: 
1. Have you in the past five years received reimbur sements, fees, funding, or salary from an 
organisation that may in any way gain or lose finan cially from the publication of this 
manuscript, either now or in the future? 
2. Do you hold any stocks or shares in an organisat ion 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 an y 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 intere sts? 
6. Do you have any non-financial competing interest s 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 det ails below. 
I have served as an advisor for Gilead (sells sofos buvir/ ledipasvir) on a single occasion. I feel 
this does not change or influence my judgement rega rding this manuscript by any means. 
I agree to the open peer review policy of the journ al. 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 o n the website along with the authors' 
responses. I agree for my report to be made availab le 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 repo rt can be included as confidential comments 
to the editors, which will not be published. 
I agree to the open peer review policy of the journ al 
Reviewer’s report 
Title:  The prevalence of functional dyspepsia using Rome III questionnaire among chronic 
hepatitis C patients. 
 
Version:  0 Date:  29 Oct 2015 
 
Reviewer:  Benjamin Misselwitz 
 
Reviewer's report: 
The study by Mohamed et al deals with the interesti ng question of extrahepatic manifestations of 
Hepatitis C. The authors identify functional dyspep sia (FD) as a frequent complaint in HCV 
infected patients; liver fibrosis seems to increase  the risk of FD further. These are new and 
relevant findings. As detailed below, the manuscrip ts suffers several shortcomings which should 
be addressed. 
 
Major comments 
- Control group. Obviously case control studies cri tically depend on a valid control group. The 
authors should report, how the control group was re cruited. It remains a limitation of the 
study that cases and controls were not recruited in  an identical way (and the authors should 
mention this as a limitation) 
- Considering the high prevalence of hepatitis C in  Egypt (15-20%?) were the healthy 
volunteers tested for HCV infection? If yes, how ma ny positive cases were found? Was 
dyspepsia also more frequent in the group of "healt hy volunteers with HCV infection"  
- Results: the statement that there was "no differe nce in the demographics" between control and 
cases (first page of results, 2nd paragraph) is a g ross misrepresentation of the data 
considering highly significant differences in age, sex, smoking, BMI 
- Discussion: one additional obvious explanation of  the observation of the authors would be 
that HCV infection causes (subclinical) depression and thus in turn increases visceral 
sensitivity and the risk for FD.  
- For an analysis as in table 4 typically a univari ate analysis is provided first. This is followed 
by a multivariate analysis for which usually non-si gnificant values are eliminated. This table 
might be a univariate analysis (and Prism 4, to the  best of my knowledge does not support 
true multivariate analysis). The authors should exp lain: Has a different program been used? 
Perhaps the authors might want to consult a statist ician. 
- Style: there are some mistakes in spelling/ gramm ar, some sentences are incomplete (for 
instance line 16 of the 2nd page of the introductio n). The manuscript should be edited by a 
native speaker (this is an urgent request) 
 
Minor points 
- Abbreviation PDS is not defined in the abstract 
- In the Methods section the authors should not pre sent the case report form of their study, 
rather the data collected should be described verba lly (or if appropriate in a table) 
- In Table 4 it should be better defined what the O R refer to: age (above or below a certain 
age?), sex (is female or male sex non-significantly  protective?), BMI (above or below a 
certain BMI?), normal or elevated ALT? 
 
Additional comment: I do not recall a single case o f a hepatitis C patient with dyspepsia (in >5 
years of clinical practice in a European tertiary c are center with a strong Hepatology unit serving 
mainly Caucasian patients); however, in my experien ce depression, dysphoria, fatigue or 
arthralgia are frequent complaints. And (as the aut hors correctly point out) dyspepsia in HCV 
infection has not been described before. This is of  course not meant to question the importance 
or validity of the results of this study. However, the discrepancy points to two interesting 
explanations: the genotype of HCV (mainly 4 in Egyp t but 1 in Europe) and/ or different 
perception of extrahepatic manifestations of HCV in  the Egyptian vs. the European/ American 
culture. It would be interesting to learn the thoug hts of the authors about this. 
 
Are the methods appropriate and well described? 
If not, please specify what is required in your com ments to the authors. 
No 
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 t he data shown? 
If not, please explain in your comments to the auth ors. 
Yes 
Are you able to assess any statistics in the manusc ript 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 manu script: 
Not suitable for publication unless extensively edi ted 
Declaration of competing interests 
Please complete a declaration of competing interest s, considering the following questions: 
1. Have you in the past five years received reimbur sements, fees, funding, or salary from an 
organisation that may in any way gain or lose finan cially from the publication of this 
manuscript, either now or in the future? 
2. Do you hold any stocks or shares in an organisat ion 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 an y 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 intere sts? 
6. Do you have any non-financial competing interest s 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 det ails below. 
I have served as an advisor for Gilead (sells sofos buvir/ ledipasvir) on a single occasion. I feel 
this does not change or influence my judgement rega rding this manuscript by any means. 
I agree to the open peer review policy of the journ al. 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 o n the website along with the authors' 
responses. I agree for my report to be made availab le 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 repo rt can be included as confidential comments 
to the editors, which will not be published. 
I agree to the open peer review policy of the journ al 
Please review this paper.
user
Reviewer’s report 
Title:  The prevalence of functional dyspepsia using Rome III questionnaire among chronic 
hepatitis C patients. 
 
Version:  0 Date:  29 Oct 2015 
 
Reviewer:  Benjamin Misselwitz 
 
Reviewer's report: 
The study by Mohamed et al deals with the interesti ng question of extrahepatic manifestations of 
Hepatitis C. The authors identify functional dyspep sia (FD) as a frequent complaint in HCV 
infected patients; liver fibrosis seems to increase  the risk of FD further. These are new and 
relevant findings. As detailed below, the manuscrip ts suffers several shortcomings which should 
be addressed. 
 
Major comments 
- Control group. Obviously case control studies cri tically depend on a valid control group. The 
authors should report, how the control group was re cruited. It remains a limitation of the 
study that cases and controls were not recruited in  an identical way (and the authors should 
mention this as a limitation) 
- Considering the high prevalence of hepatitis C in  Egypt (15-20%?) were the healthy 
volunteers tested for HCV infection? If yes, how ma ny positive cases were found? Was 
dyspepsia also more frequent in the group of "healt hy volunteers with HCV infection"  
- Results: the statement that there was "no differe nce in the demographics" between control and 
cases (first page of results, 2nd paragraph) is a g ross misrepresentation of the data 
considering highly significant differences in age, sex, smoking, BMI 
- Discussion: one additional obvious explanation of  the observation of the authors would be 
that HCV infection causes (subclinical) depression and thus in turn increases visceral 
sensitivity and the risk for FD.  
- For an analysis as in table 4 typically a univari ate analysis is provided first. This is followed 
by a multivariate analysis for which usually non-si gnificant values are eliminated. This table 
might be a univariate analysis (and Prism 4, to the  best of my knowledge does not support 
true multivariate analysis). The authors should exp lain: Has a different program been used? 
Perhaps the authors might want to consult a statist ician. 
- Style: there are some mistakes in spelling/ gramm ar, some sentences are incomplete (for 
instance line 16 of the 2nd page of the introductio n). The manuscript should be edited by a 
native speaker (this is an urgent request) 
 
Minor points 
- Abbreviation PDS is not defined in the abstract 
- In the Methods section the authors should not pre sent the case report form of their study, 
rather the data collected should be described verba lly (or if appropriate in a table) 
- In Table 4 it should be better defined what the O R refer to: age (above or below a certain 
age?), sex (is female or male sex non-significantly  protective?), BMI (above or below a 
certain BMI?), normal or elevated ALT? 
 
Additional comment: I do not recall a single case o f a hepatitis C patient with dyspepsia (in >5 
years of clinical practice in a European tertiary c are center with a strong Hepatology unit serving 
mainly Caucasian patients); however, in my experien ce depression, dysphoria, fatigue or 
arthralgia are frequent complaints. And (as the aut hors correctly point out) dyspepsia in HCV 
infection has not been described before. This is of  course not meant to question the importance 
or validity of the results of this study. However, the discrepancy points to two interesting 
explanations: the genotype of HCV (mainly 4 in Egyp t but 1 in Europe) and/ or different 
perception of extrahepatic manifestations of HCV in  the Egyptian vs. the European/ American 
culture. It would be interesting to learn the thoug hts of the authors about this. 
 
Are the methods appropriate and well described? 
If not, please specify what is required in your com ments to the authors. 
No 
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 t he data shown? 
If not, please explain in your comments to the auth ors. 
Yes 
Are you able to assess any statistics in the manusc ript 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 manu script: 
Not suitable for publication unless extensively edi ted 
Declaration of competing interests 
Please complete a declaration of competing interest s, considering the following questions: 
1. Have you in the past five years received reimbur sements, fees, funding, or salary from an 
organisation that may in any way gain or lose finan cially from the publication of this 
manuscript, either now or in the future? 
2. Do you hold any stocks or shares in an organisat ion 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 an y 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 intere sts? 
6. Do you have any non-financial competing interest s 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 det ails below. 
I have served as an advisor for Gilead (sells sofos buvir/ ledipasvir) on a single occasion. I feel 
this does not change or influence my judgement rega rding this manuscript by any means. 
I agree to the open peer review policy of the journ al. 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 o n the website along with the authors' 
responses. I agree for my report to be made availab le 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 repo rt can be included as confidential comments 
to the editors, which will not be published. 
I agree to the open peer review policy of the journ al 
assistant