Reviewer ’s report  
 
Title:  Health -Related Quality of Life in patients with chronic hepatitis C receiving Sofosbuvir -
Based Treatment, with and without Interferon: a prospective observational study in Egypt  
 
Version: 0 Date: 23 Nov 2016 
 
Reviewer:  Shivani  Mhatre  
 
Reviewer’s report:  
 
The manuscript by Youssef et al. described the effect of directly acting antiviral (DAA) therapies 
among chronic hepatitis C patients using patient reported outcomes (PROs). Although for the 
most part, the dat a is straightforward and convincing, it would help to consider the following 
comments and make the appropriate changes in the text.  
 
 
General suggestions:  
 
1. Please mention all the objectives clearly in the abstract as well as the objective section.  
 
2. The treatment categories 'dual/triple' and 'interferon -free/interferon containing' are used 
interchangeably throughout the manuscript. Please be consistent; recommendation to use 'dual 
therapy' and 'triple therapy' after defining them in the treatment p rotocol.  
 
3. After spelling out HRQoL, please use abbreviations for rest of the document.  
 
5. Please spell out the abbreviated terms as footnotes below the tables  
 
 
Suggestions by sections:  
 
Abstract:  
 
1. Prospective is not a type of study design. This is an observation study and outcomes/PRO 
data was collected prospectively. Please consider revising to 'prospective observational study'.  
2. It is not cleat that LDSI is measuring HRQoL. Please consider either describing the 
instrument used to measure HRQoL in t he methods section or using name of the actual 
instrument in the results section.  
 
3. Please define triple and dual therapy patients before using the terms in the results section.  
 
4. Please spell out BMI before using the abbreviation.  
 
5. Is the outcome meas ured using the Depression Anxiety Stress Scales called anxiety in 
line 28 and stress in line 35 or is the author referring to the scale sub -domains?  
6. Before reading the conclusion section, it was unclear that interferon and non -interferon 
containing ther apies will be compared. Due to the word limit, it may not be possible to define all 
objectives clearly in the abstract. But if the results of an objective are important enough to be 
included in the conclusion section, the author may want to briefly mention  the objective earlier.  
 
 
Introduction:  
 
7. Reference #7 is from employee's perspective and does not evaluate PROs.Is this citation 
used due to mention of lower HRQoL in the background session (citations 7 -13) of reference #7? 
In general, it is highly recom mended that the author use the original paper for reference and 
citation.  
 
8. Please provide reference for statement ending on page 1 line 41.  
 
9. Optional: concise the 4 paragraphs on HCV treatments into 1 -2 paragraphs to reflect only 
the key background inf ormation.  
 
 
Objectives:  
 
10.  For objective 1: PROs were compared between the 2 regimen users and not of the 
regimens itself. Please consider rephrasing the statement.  
 
11. For objective 2: Please elaborate on the specific PROs for the first objective instea d of 
the second.  
 
12. For objective 2: Ideally, a sub -group analysis follows a all -sample analysis. Since DAA 
therapy users formed the total sample and dual/triple therapy users were the sub -groups, please 
consider switching the order of the objectives.  
 
13. For objective 3: Please clarify the patient group - all, interferon users, non -interferon 
users, DAA therapy users or a combination of any of these?  
 
 
Methods:  
 
Study design and population:  
 
14.  Please consider rephrasing the study design and population section to streamline the 
flow. The section starts with the study design, described briefly about the patient selection, then 
the data collection, followed by the final patient count, and agai n in detail about the patient 
selection criteria and then the clinic.  
 
Consider using the following framework:  
 
- Study design  
 
- Study population - location and selection criteria  
 
- Data collection from the patients (time and method)  
 
Note: Final patient co unts are ideally mentioned in the resu lts section.  
 
15.  Line 26: Please clarify if the patients recommended to be treated for short treatment 
periods based on some guidelines, if the study patients were treated for short treatment periods 
based on the stu dy protocol (if yes, this is not an observational study), or if the 3 -6 months data 
is based on current practice data? Please cite a reference, if available.  
 
16.  Please define the T0, T1 and T3 terms in the same statement. T2 is introduced in the first 
paragraph while T0 and T1 are introduced in the next paragraph.  
 
17.  Would 'no prior HCV treatment' and 'eligibility for starting DAA treatment' be other 
selection criteria?  
 
 
Protocol of therapy:  
 
18.  Please provide definition of interferon eligibility.  
 
 
Data collection:  
 
19.  Since measurement of mental health is one of the objectives, please specify that the 
DASS was used to assess mental health.  
 
 
Results:  
 
20.  How is treatment naive defined? Did the treatment naive patients have no prior treatment 
at T0 whi le the experienced patients were on a non -DAA HCV treatment at T0?  
 
21.  Please justify combining results from treatment naïve patients with others. PROs are 
highly dependent on the treatment duration. If the PRO scores of the treatment naïve and 
experience d patients at T0 are very different, then that would imply potential dilution of results.  
 
22.  One of the reasons for non -significance of results can be the sample size. A post -hoc 
sample size calculation would help to identify this.  
 
23.  Page 10, line 42:  There is no mention of 4 weeks evaluation time in the methods section; 
T1 is defined at 5 -6 weeks. Please clarify.  
 
Discussion:  
 
24.  Aim 2: It is interesting that all PRO scores that significantly increase from T0 to T1, are 
lowered from T1 to T2. A brief discussion on this phenomena would be interesting.  
 
 
Potential limitations:  
 
25.   Please mention the impact of small sample size on significance of the results  
 
 
Conclusions:  
 
26.   Please summarize the key results in this section before describing the study importance.  
 
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.  
 
Unable to assess  
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional stat istical 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:  
 
Needs some language corrections before being publi shed 
 
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 thi s 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 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.  
 
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 unde r 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:  Health -Related Quality of Life in patients with chronic hepatitis C receiving Sofosbuvir -
Based Treatment, with and without Interferon: a prospective observational study in Egypt  
 
Version: 0 Date: 23 Nov 2016 
 
Reviewer:  Shivani  Mhatre  
 
Reviewer’s report:  
 
The manuscript by Youssef et al. described the effect of directly acting antiviral (DAA) therapies 
among chronic hepatitis C patients using patient reported outcomes (PROs). Although for the 
most part, the dat a is straightforward and convincing, it would help to consider the following 
comments and make the appropriate changes in the text.  
 
 
General suggestions:  
 
1. Please mention all the objectives clearly in the abstract as well as the objective section.  
 
2. The treatment categories 'dual/triple' and 'interferon -free/interferon containing' are used 
interchangeably throughout the manuscript. Please be consistent; recommendation to use 'dual 
therapy' and 'triple therapy' after defining them in the treatment p rotocol.  
 
3. After spelling out HRQoL, please use abbreviations for rest of the document.  
 
5. Please spell out the abbreviated terms as footnotes below the tables  
 
 
Suggestions by sections:  
 
Abstract:  
 
1. Prospective is not a type of study design. This is an observation study and outcomes/PRO 
data was collected prospectively. Please consider revising to 'prospective observational study'.  
2. It is not cleat that LDSI is measuring HRQoL. Please consider either describing the 
instrument used to measure HRQoL in t he methods section or using name of the actual 
instrument in the results section.  
 
3. Please define triple and dual therapy patients before using the terms in the results section.  
 
4. Please spell out BMI before using the abbreviation.  
 
5. Is the outcome meas ured using the Depression Anxiety Stress Scales called anxiety in 
line 28 and stress in line 35 or is the author referring to the scale sub -domains?  
6. Before reading the conclusion section, it was unclear that interferon and non -interferon 
containing ther apies will be compared. Due to the word limit, it may not be possible to define all 
objectives clearly in the abstract. But if the results of an objective are important enough to be 
included in the conclusion section, the author may want to briefly mention  the objective earlier.  
 
 
Introduction:  
 
7. Reference #7 is from employee's perspective and does not evaluate PROs.Is this citation 
used due to mention of lower HRQoL in the background session (citations 7 -13) of reference #7? 
In general, it is highly recom mended that the author use the original paper for reference and 
citation.  
 
8. Please provide reference for statement ending on page 1 line 41.  
 
9. Optional: concise the 4 paragraphs on HCV treatments into 1 -2 paragraphs to reflect only 
the key background inf ormation.  
 
 
Objectives:  
 
10.  For objective 1: PROs were compared between the 2 regimen users and not of the 
regimens itself. Please consider rephrasing the statement.  
 
11. For objective 2: Please elaborate on the specific PROs for the first objective instea d of 
the second.  
 
12. For objective 2: Ideally, a sub -group analysis follows a all -sample analysis. Since DAA 
therapy users formed the total sample and dual/triple therapy users were the sub -groups, please 
consider switching the order of the objectives.  
 
13. For objective 3: Please clarify the patient group - all, interferon users, non -interferon 
users, DAA therapy users or a combination of any of these?  
 
 
Methods:  
 
Study design and population:  
 
14.  Please consider rephrasing the study design and population section to streamline the 
flow. The section starts with the study design, described briefly about the patient selection, then 
the data collection, followed by the final patient count, and agai n in detail about the patient 
selection criteria and then the clinic.  
 
Consider using the following framework:  
 
- Study design  
 
- Study population - location and selection criteria  
 
- Data collection from the patients (time and method)  
 
Note: Final patient co unts are ideally mentioned in the resu lts section.  
 
15.  Line 26: Please clarify if the patients recommended to be treated for short treatment 
periods based on some guidelines, if the study patients were treated for short treatment periods 
based on the stu dy protocol (if yes, this is not an observational study), or if the 3 -6 months data 
is based on current practice data? Please cite a reference, if available.  
 
16.  Please define the T0, T1 and T3 terms in the same statement. T2 is introduced in the first 
paragraph while T0 and T1 are introduced in the next paragraph.  
 
17.  Would 'no prior HCV treatment' and 'eligibility for starting DAA treatment' be other 
selection criteria?  
 
 
Protocol of therapy:  
 
18.  Please provide definition of interferon eligibility.  
 
 
Data collection:  
 
19.  Since measurement of mental health is one of the objectives, please specify that the 
DASS was used to assess mental health.  
 
 
Results:  
 
20.  How is treatment naive defined? Did the treatment naive patients have no prior treatment 
at T0 whi le the experienced patients were on a non -DAA HCV treatment at T0?  
 
21.  Please justify combining results from treatment naïve patients with others. PROs are 
highly dependent on the treatment duration. If the PRO scores of the treatment naïve and 
experience d patients at T0 are very different, then that would imply potential dilution of results.  
 
22.  One of the reasons for non -significance of results can be the sample size. A post -hoc 
sample size calculation would help to identify this.  
 
23.  Page 10, line 42:  There is no mention of 4 weeks evaluation time in the methods section; 
T1 is defined at 5 -6 weeks. Please clarify.  
 
Discussion:  
 
24.  Aim 2: It is interesting that all PRO scores that significantly increase from T0 to T1, are 
lowered from T1 to T2. A brief discussion on this phenomena would be interesting.  
 
 
Potential limitations:  
 
25.   Please mention the impact of small sample size on significance of the results  
 
 
Conclusions:  
 
26.   Please summarize the key results in this section before describing the study importance.  
 
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.  
 
Unable to assess  
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional stat istical 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:  
 
Needs some language corrections before being publi shed 
 
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 thi s 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 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.  
 
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 unde r 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:  Health -Related Quality of Life in patients with chronic hepatitis C receiving Sofosbuvir -
Based Treatment, with and without Interferon: a prospective observational study in Egypt  
 
Version: 0 Date: 23 Nov 2016 
 
Reviewer:  Shivani  Mhatre  
 
Reviewer’s report:  
 
The manuscript by Youssef et al. described the effect of directly acting antiviral (DAA) therapies 
among chronic hepatitis C patients using patient reported outcomes (PROs). Although for the 
most part, the dat a is straightforward and convincing, it would help to consider the following 
comments and make the appropriate changes in the text.  
 
 
General suggestions:  
 
1. Please mention all the objectives clearly in the abstract as well as the objective section.  
 
2. The treatment categories 'dual/triple' and 'interferon -free/interferon containing' are used 
interchangeably throughout the manuscript. Please be consistent; recommendation to use 'dual 
therapy' and 'triple therapy' after defining them in the treatment p rotocol.  
 
3. After spelling out HRQoL, please use abbreviations for rest of the document.  
 
5. Please spell out the abbreviated terms as footnotes below the tables  
 
 
Suggestions by sections:  
 
Abstract:  
 
1. Prospective is not a type of study design. This is an observation study and outcomes/PRO 
data was collected prospectively. Please consider revising to 'prospective observational study'.  
2. It is not cleat that LDSI is measuring HRQoL. Please consider either describing the 
instrument used to measure HRQoL in t he methods section or using name of the actual 
instrument in the results section.  
 
3. Please define triple and dual therapy patients before using the terms in the results section.  
 
4. Please spell out BMI before using the abbreviation.  
 
5. Is the outcome meas ured using the Depression Anxiety Stress Scales called anxiety in 
line 28 and stress in line 35 or is the author referring to the scale sub -domains?  
6. Before reading the conclusion section, it was unclear that interferon and non -interferon 
containing ther apies will be compared. Due to the word limit, it may not be possible to define all 
objectives clearly in the abstract. But if the results of an objective are important enough to be 
included in the conclusion section, the author may want to briefly mention  the objective earlier.  
 
 
Introduction:  
 
7. Reference #7 is from employee's perspective and does not evaluate PROs.Is this citation 
used due to mention of lower HRQoL in the background session (citations 7 -13) of reference #7? 
In general, it is highly recom mended that the author use the original paper for reference and 
citation.  
 
8. Please provide reference for statement ending on page 1 line 41.  
 
9. Optional: concise the 4 paragraphs on HCV treatments into 1 -2 paragraphs to reflect only 
the key background inf ormation.  
 
 
Objectives:  
 
10.  For objective 1: PROs were compared between the 2 regimen users and not of the 
regimens itself. Please consider rephrasing the statement.  
 
11. For objective 2: Please elaborate on the specific PROs for the first objective instea d of 
the second.  
 
12. For objective 2: Ideally, a sub -group analysis follows a all -sample analysis. Since DAA 
therapy users formed the total sample and dual/triple therapy users were the sub -groups, please 
consider switching the order of the objectives.  
 
13. For objective 3: Please clarify the patient group - all, interferon users, non -interferon 
users, DAA therapy users or a combination of any of these?  
 
 
Methods:  
 
Study design and population:  
 
14.  Please consider rephrasing the study design and population section to streamline the 
flow. The section starts with the study design, described briefly about the patient selection, then 
the data collection, followed by the final patient count, and agai n in detail about the patient 
selection criteria and then the clinic.  
 
Consider using the following framework:  
 
- Study design  
 
- Study population - location and selection criteria  
 
- Data collection from the patients (time and method)  
 
Note: Final patient co unts are ideally mentioned in the resu lts section.  
 
15.  Line 26: Please clarify if the patients recommended to be treated for short treatment 
periods based on some guidelines, if the study patients were treated for short treatment periods 
based on the stu dy protocol (if yes, this is not an observational study), or if the 3 -6 months data 
is based on current practice data? Please cite a reference, if available.  
 
16.  Please define the T0, T1 and T3 terms in the same statement. T2 is introduced in the first 
paragraph while T0 and T1 are introduced in the next paragraph.  
 
17.  Would 'no prior HCV treatment' and 'eligibility for starting DAA treatment' be other 
selection criteria?  
 
 
Protocol of therapy:  
 
18.  Please provide definition of interferon eligibility.  
 
 
Data collection:  
 
19.  Since measurement of mental health is one of the objectives, please specify that the 
DASS was used to assess mental health.  
 
 
Results:  
 
20.  How is treatment naive defined? Did the treatment naive patients have no prior treatment 
at T0 whi le the experienced patients were on a non -DAA HCV treatment at T0?  
 
21.  Please justify combining results from treatment naïve patients with others. PROs are 
highly dependent on the treatment duration. If the PRO scores of the treatment naïve and 
experience d patients at T0 are very different, then that would imply potential dilution of results.  
 
22.  One of the reasons for non -significance of results can be the sample size. A post -hoc 
sample size calculation would help to identify this.  
 
23.  Page 10, line 42:  There is no mention of 4 weeks evaluation time in the methods section; 
T1 is defined at 5 -6 weeks. Please clarify.  
 
Discussion:  
 
24.  Aim 2: It is interesting that all PRO scores that significantly increase from T0 to T1, are 
lowered from T1 to T2. A brief discussion on this phenomena would be interesting.  
 
 
Potential limitations:  
 
25.   Please mention the impact of small sample size on significance of the results  
 
 
Conclusions:  
 
26.   Please summarize the key results in this section before describing the study importance.  
 
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.  
 
Unable to assess  
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional stat istical 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:  
 
Needs some language corrections before being publi shed 
 
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 thi s 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 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.  
 
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 unde r 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