Reviewer ’s report  
 
Title: Non-alcoholic fatty liver disease and its associations among adolescents in an urban, Sri 
Lankan community  
 
Version: 0 Date: 03 Aug 2017  
 
Reviewer: Oyekoya Ayonrinde  
 
Reviewer's report:  
 
This manuscript by Professor Rajindrajith and collea gues examines the associations between 
ultrasound -diagnosed non -alcoholic fatty liver disease (NAFLD) and metabolic features in 14 
year old community -based adolescents and their parents in urban Sri Lanka. The authors also 
explore relationships between fam ily sociodemographic characteristics, duration of gestation and 
the duration of breastfeeding, on a diagnosis of NAFLD in the study population when aged 14 
years. There are increasing population -based studies regarding NAFLD in children and 
adolescents fro m predominantly "Caucasian" and some Asian populations amongst others, there 
are few data regarding NAFLD in Sri Lankan adolescents.  
The most interesting aspects of this study are the population base, large number of age -matched 
subjects, use of ultrasou nd to ascertain the diagnosis of fatty liver, available metabolic blood 
parameters and the sociodemographic data. Nevertheless, I have some concerns with this 
manuscript as detailed below.  
 
Minor comments:  
1. Page 6, line 15 - note NAFLD has potential to c ause irreversible liver damage and cirrhosis 
in a minority of individuals, so the comment as it appears is rather alarmist and inacurrate.  
2. Page 6, line 20 - MetS has potential for or increased risk of serious long term consequences. 
These are not inevit able and this should be reworded.  
3. Page 6, lines 31 -38 - references 4 and 5 do not appear to be adequate for the rise of MetS in 
adolescents. There are also more recent data of relevance.  
4. While the response rate of 50% for an invited study is good, it  is worthwhile specifying if the 
participants are representative of the broader population in that town.  
5. Page 13 line 57 - NAFLD is a disease mainly in affluent societies. It is increasing in 
incidence and prevalence in most countries.  
6. Page 14 - since  low HDL cholesterol level is the main lipoprotein component associated with 
NAFLD that should be included.  
7. Table 1 - please state the reference currency.  
8. Table 1 - note that the numbers used as denominators for the controls do not add up to the 
expe cted number. Why is there so much missing data and how was it accounted for?  
9. Table 1 - Same comment regarding ascertainment of duration of breastfeeding. Is the third 
row under breastfeeding meant to be 5 -6 months? Otherwise there are some data missing.  
Table 2 - There is missing data not explained for. Also, was race specific BMI and waist 
circumference considered in defining obesity, as it is different from that of Caucasians.  
Table 2 - please include systolic and diastolic blood pressure separately as  individual 
components of the metabolic syndrome.  
Table 4 - again explain for the denominators and missing data.  
Figure 1 is a bit lost, since there is little detail of the fat distribution assessment in the methods  
 
Major comments:  
1. The methods section on pages 8 -9 does not show details of how the data on parents was 
collected, what proportion were collected, details of age, medical history or medications for 
metabolic syndrome features (waist circumference/ obesity, fasting glucose level, history of 
type II diabetes or treatment for diabetes, sociodemographic characeristics or how the 
duration of breastfeeding was ascertained (given the likely recall bias of parents 14 years 
later).  
2. Methods section on pages 8 -9 - It is inadequate to state that blood pressure, anthropometric 
measurements and total body fat content were measured using standard techniques. Please 
provide details of the assessments performed.  
3. Methods section, page 9 - The liver ultrasounds were performed by 5 doctors. Are they 
speciali st radiologists or non -specialist ultrasound practitioners? It would have been useful to 
have performed inter -observer reliability tests to provide confidence in the ultrasound 
reporting, given the number of ultrasound practitioners. I note this has been c ommented on in 
the study limitations.  
4. Page 9 - were both systolic and diastolic blood pressure recoreded as part of the metabolic 
syndrome?  
5. Page 11 - the first paragraph of results (lines 7 -9) doesn't make sense. I suspect the authors 
meant to say 2 subjects were excluded, having not consented to ultrasound. Also, out of 506 
there were 42 with fatty liver on ultrasound, suggesting that 464 did not, yet line 14 states 
that 380 adolescents did not have features of fatty liver and served as controls i.e.  the 
numbers are confusing and do not add up.  
6. Page 11, lines 55 -58 - how was the family history of components of MetS ascertained?  
7. The adolescent cohort characteristics should be summarised in a master table (Table 1).  
8. The blood test results are n ot presented in sufficient detail.  
9. The total body fat content results are not presented.  
10. There is abundant recent published data regarding adolescent NAFLD, including associations 
with the duration of breastfeeding. A more up to date literature review is recommended.  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comment s 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 revi ew? 
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 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  
financi ally 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, funding, or salary from an organiz ation 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 th e 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: Non-alcoholic fatty liver disease and its associations among adolescents in an urban, Sri 
Lankan community  
 
Version: 0 Date: 03 Aug 2017  
 
Reviewer: Oyekoya Ayonrinde  
 
Reviewer's report:  
 
This manuscript by Professor Rajindrajith and collea gues examines the associations between 
ultrasound -diagnosed non -alcoholic fatty liver disease (NAFLD) and metabolic features in 14 
year old community -based adolescents and their parents in urban Sri Lanka. The authors also 
explore relationships between fam ily sociodemographic characteristics, duration of gestation and 
the duration of breastfeeding, on a diagnosis of NAFLD in the study population when aged 14 
years. There are increasing population -based studies regarding NAFLD in children and 
adolescents fro m predominantly "Caucasian" and some Asian populations amongst others, there 
are few data regarding NAFLD in Sri Lankan adolescents.  
The most interesting aspects of this study are the population base, large number of age -matched 
subjects, use of ultrasou nd to ascertain the diagnosis of fatty liver, available metabolic blood 
parameters and the sociodemographic data. Nevertheless, I have some concerns with this 
manuscript as detailed below.  
 
Minor comments:  
1. Page 6, line 15 - note NAFLD has potential to c ause irreversible liver damage and cirrhosis 
in a minority of individuals, so the comment as it appears is rather alarmist and inacurrate.  
2. Page 6, line 20 - MetS has potential for or increased risk of serious long term consequences. 
These are not inevit able and this should be reworded.  
3. Page 6, lines 31 -38 - references 4 and 5 do not appear to be adequate for the rise of MetS in 
adolescents. There are also more recent data of relevance.  
4. While the response rate of 50% for an invited study is good, it  is worthwhile specifying if the 
participants are representative of the broader population in that town.  
5. Page 13 line 57 - NAFLD is a disease mainly in affluent societies. It is increasing in 
incidence and prevalence in most countries.  
6. Page 14 - since  low HDL cholesterol level is the main lipoprotein component associated with 
NAFLD that should be included.  
7. Table 1 - please state the reference currency.  
8. Table 1 - note that the numbers used as denominators for the controls do not add up to the 
expe cted number. Why is there so much missing data and how was it accounted for?  
9. Table 1 - Same comment regarding ascertainment of duration of breastfeeding. Is the third 
row under breastfeeding meant to be 5 -6 months? Otherwise there are some data missing.  
Table 2 - There is missing data not explained for. Also, was race specific BMI and waist 
circumference considered in defining obesity, as it is different from that of Caucasians.  
Table 2 - please include systolic and diastolic blood pressure separately as  individual 
components of the metabolic syndrome.  
Table 4 - again explain for the denominators and missing data.  
Figure 1 is a bit lost, since there is little detail of the fat distribution assessment in the methods  
 
Major comments:  
1. The methods section on pages 8 -9 does not show details of how the data on parents was 
collected, what proportion were collected, details of age, medical history or medications for 
metabolic syndrome features (waist circumference/ obesity, fasting glucose level, history of 
type II diabetes or treatment for diabetes, sociodemographic characeristics or how the 
duration of breastfeeding was ascertained (given the likely recall bias of parents 14 years 
later).  
2. Methods section on pages 8 -9 - It is inadequate to state that blood pressure, anthropometric 
measurements and total body fat content were measured using standard techniques. Please 
provide details of the assessments performed.  
3. Methods section, page 9 - The liver ultrasounds were performed by 5 doctors. Are they 
speciali st radiologists or non -specialist ultrasound practitioners? It would have been useful to 
have performed inter -observer reliability tests to provide confidence in the ultrasound 
reporting, given the number of ultrasound practitioners. I note this has been c ommented on in 
the study limitations.  
4. Page 9 - were both systolic and diastolic blood pressure recoreded as part of the metabolic 
syndrome?  
5. Page 11 - the first paragraph of results (lines 7 -9) doesn't make sense. I suspect the authors 
meant to say 2 subjects were excluded, having not consented to ultrasound. Also, out of 506 
there were 42 with fatty liver on ultrasound, suggesting that 464 did not, yet line 14 states 
that 380 adolescents did not have features of fatty liver and served as controls i.e.  the 
numbers are confusing and do not add up.  
6. Page 11, lines 55 -58 - how was the family history of components of MetS ascertained?  
7. The adolescent cohort characteristics should be summarised in a master table (Table 1).  
8. The blood test results are n ot presented in sufficient detail.  
9. The total body fat content results are not presented.  
10. There is abundant recent published data regarding adolescent NAFLD, including associations 
with the duration of breastfeeding. A more up to date literature review is recommended.  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comment s 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 revi ew? 
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 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  
financi ally 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, funding, or salary from an organiz ation 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 th e 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: Non-alcoholic fatty liver disease and its associations among adolescents in an urban, Sri 
Lankan community  
 
Version: 0 Date: 03 Aug 2017  
 
Reviewer: Oyekoya Ayonrinde  
 
Reviewer's report:  
 
This manuscript by Professor Rajindrajith and collea gues examines the associations between 
ultrasound -diagnosed non -alcoholic fatty liver disease (NAFLD) and metabolic features in 14 
year old community -based adolescents and their parents in urban Sri Lanka. The authors also 
explore relationships between fam ily sociodemographic characteristics, duration of gestation and 
the duration of breastfeeding, on a diagnosis of NAFLD in the study population when aged 14 
years. There are increasing population -based studies regarding NAFLD in children and 
adolescents fro m predominantly "Caucasian" and some Asian populations amongst others, there 
are few data regarding NAFLD in Sri Lankan adolescents.  
The most interesting aspects of this study are the population base, large number of age -matched 
subjects, use of ultrasou nd to ascertain the diagnosis of fatty liver, available metabolic blood 
parameters and the sociodemographic data. Nevertheless, I have some concerns with this 
manuscript as detailed below.  
 
Minor comments:  
1. Page 6, line 15 - note NAFLD has potential to c ause irreversible liver damage and cirrhosis 
in a minority of individuals, so the comment as it appears is rather alarmist and inacurrate.  
2. Page 6, line 20 - MetS has potential for or increased risk of serious long term consequences. 
These are not inevit able and this should be reworded.  
3. Page 6, lines 31 -38 - references 4 and 5 do not appear to be adequate for the rise of MetS in 
adolescents. There are also more recent data of relevance.  
4. While the response rate of 50% for an invited study is good, it  is worthwhile specifying if the 
participants are representative of the broader population in that town.  
5. Page 13 line 57 - NAFLD is a disease mainly in affluent societies. It is increasing in 
incidence and prevalence in most countries.  
6. Page 14 - since  low HDL cholesterol level is the main lipoprotein component associated with 
NAFLD that should be included.  
7. Table 1 - please state the reference currency.  
8. Table 1 - note that the numbers used as denominators for the controls do not add up to the 
expe cted number. Why is there so much missing data and how was it accounted for?  
9. Table 1 - Same comment regarding ascertainment of duration of breastfeeding. Is the third 
row under breastfeeding meant to be 5 -6 months? Otherwise there are some data missing.  
Table 2 - There is missing data not explained for. Also, was race specific BMI and waist 
circumference considered in defining obesity, as it is different from that of Caucasians.  
Table 2 - please include systolic and diastolic blood pressure separately as  individual 
components of the metabolic syndrome.  
Table 4 - again explain for the denominators and missing data.  
Figure 1 is a bit lost, since there is little detail of the fat distribution assessment in the methods  
 
Major comments:  
1. The methods section on pages 8 -9 does not show details of how the data on parents was 
collected, what proportion were collected, details of age, medical history or medications for 
metabolic syndrome features (waist circumference/ obesity, fasting glucose level, history of 
type II diabetes or treatment for diabetes, sociodemographic characeristics or how the 
duration of breastfeeding was ascertained (given the likely recall bias of parents 14 years 
later).  
2. Methods section on pages 8 -9 - It is inadequate to state that blood pressure, anthropometric 
measurements and total body fat content were measured using standard techniques. Please 
provide details of the assessments performed.  
3. Methods section, page 9 - The liver ultrasounds were performed by 5 doctors. Are they 
speciali st radiologists or non -specialist ultrasound practitioners? It would have been useful to 
have performed inter -observer reliability tests to provide confidence in the ultrasound 
reporting, given the number of ultrasound practitioners. I note this has been c ommented on in 
the study limitations.  
4. Page 9 - were both systolic and diastolic blood pressure recoreded as part of the metabolic 
syndrome?  
5. Page 11 - the first paragraph of results (lines 7 -9) doesn't make sense. I suspect the authors 
meant to say 2 subjects were excluded, having not consented to ultrasound. Also, out of 506 
there were 42 with fatty liver on ultrasound, suggesting that 464 did not, yet line 14 states 
that 380 adolescents did not have features of fatty liver and served as controls i.e.  the 
numbers are confusing and do not add up.  
6. Page 11, lines 55 -58 - how was the family history of components of MetS ascertained?  
7. The adolescent cohort characteristics should be summarised in a master table (Table 1).  
8. The blood test results are n ot presented in sufficient detail.  
9. The total body fat content results are not presented.  
10. There is abundant recent published data regarding adolescent NAFLD, including associations 
with the duration of breastfeeding. A more up to date literature review is recommended.  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comment s 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 revi ew? 
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 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  
financi ally 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, funding, or salary from an organiz ation 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 th e 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