Reviewer ’s report  
 
Title:  Metabolic syndrome and biochemical changes among Non -Alcoholic Fatty Liver disease 
patients attending a tertiary c are hospital of Nepal  
 
Version: 0 Date: 15 Mar 2018 
 
Reviewer:  Amedeo  Lonardo  
 
Reviewer’s report:  
 
GENERAL COMMENT  
 
The amount of novel information is quite negligible. However, this study fills in a gap relative to 
the specific geographical area.  There are ser ious misconceptions regarding the relationship of 
NAFLD with the MetS, the diagnosis and pathogenesis of NAFLD and its association with 
raised liver enzymes. References are outdated and must be improved. English should carefully be 
edited.  
 
 
SPECIFIC COMMEN T 
 
This manuscript is not written in idiomatic English and must carefully be edited by a native 
English speaker/professional agency. There are several examples of sentences to be rephrase. 
Just to quote a few:  
 
"With a long history of discovery nearly 60 ye ars ago, nonalcoholic fatty liver disease (NAFLD)  
has emerged as the most common liver disease these days";  "NAFLD constitutes abnormal 
accumulation of fat in the liver without the considerable abuse of alcohol"; etc  
 
"NAFLD recognizable as the hepatic ma nifestation of metabolic syndrome" - and "Nowadays, 
NAFLD has been considered as hepatic compon ent of metabolic syndrome (MS)"  
 
 First: avoid repetiotions; Second and more important: this definitely is an outdated paradigm. 
Indeed NAFLD is mutually and bidi rectionally linked with MetS of which it is both the cause 
and the consequence (J Hepatol. 2018 Feb;68(2):335 -352.).  
 
 
mechanism of such  pathology is yet to be explored  
 
 Please, refer to more updated articles from the same group (e.g. Dig Liver Dis. 2017;49 :471-
483).  
 
 
"elevated transaminases and histo -pathological changes are well explained in NAFLD"  
 
- sentence unclear. Please rephrase.  
 
 
"Tan et al (9) suggested IDF criteria is applicable in an Asian population for risk assessment of 
MS 
 
while Pokharel et al  (10) suggests NCEP/ATP III to be specific for MS in our population but not  
applicable."  
 
- These Authors may be willing to explain what this statement has to do with the previous one 
""elevated transaminases and histo -pathological changes are well explaine d in NAFLD".  
 
 
"Liver biopsy remains the gold standard method for the diagnosis of hepatic steotosis and helps 
in exclusion from secondary etiology of liver injury"  
 
- These Authors may be wiiling to acknowledge that, histologically, NAFLD is 
indistinguishab le from Alcoholic liver disease.  
 
 
"The development of new inventions in the technology has given the alternatives to screen the 
patients without much of inconvenience like ultrasonography, computed tomography, magnetic 
resonance imaging, transient elastogr aphy. Due to cost -effectiveness and availability of 
ultrasonography, it is widely used to detect and grade NAFLD in our country"  
 
 Please, provide supporting references (e.g. Expert Rev Gastroenterol Hepatol. 2018;12:351 -
367) and briefly allude to the benef its of semi -quantitative US indices (Metabolism. 2017 
Jul;72:57 -65). 
 
 
"There is also an increase in the triglyceride and low density lipoprotein (LDL) level posing a  
cardiovascular risk (13)."  
 
 The mechanisms underlying excess cardiovascular risk in these NAFLD patients is much 
more complex than that and involves both generic mechanisms associated with the MetS and 
others specifically associated with NAFLD (J Hepatol. 2018 Feb;68(2):335 -352.; Nat Rev 
Endocrinol. 2018 Feb;14(2):99 -114).  
 
 
"Diagnosis of NAFLD  was made by abdominal ultrasonography."  
 
 This is a misconception which should be reworked. The diagnosis of NAFLD is based on 
imaging (fatty liver) IN THE ABSENCE OF COMPETING CAUSES OF STEATOSIS (J 
Hepatol. 2016;65:643 -4. J Hepatol. 2013;59:859 -71) . Ple ase, link this section with the next one 
(Inclusion/exclusion criteria) in order to avoid repetitions and misunderstandings.  
 
"Grading was done based on the standard criteria accepted by American, Gastroenterology 
Association."  
 
- Reference ?  
 
 
Patients with normal abdominal ultrasonography were categorized as control  
 
 Where these controls subjected to any lab. Assessment ?  
 
 
MMTH  
 
 Please, define when used for the first time.  
 
 
The study was carried out in Manmohan Memorial Teaching Hospital  
 
 the abbrieviation should be used here.  
 
 
all liver enzymes and lipid profile parameters showed significant statistical elevation  
among NAFLD patients.  
 
- The comment on liver enzymes results from the inclusion/exclusion criteria. In other words it 
mirrors the se lection done rather than being a findings.  
 
 
"non significant rise in creatinine and decrease in urea were observed among NAFLD patient" 
"furthermore, none of the hematological changes were significant in NAFLD and control 
population".  
 
 omit any comment on non-significant findings.  
 
 
The discussion should be reworked. Delete the following section "NAFLD, an appalling public 
health problem, is considered as one of the most common cause of liver disease, especially 
among obese and type 2 diabetic population (18 ) .The prevalence of NAFLD is constantly 
increasing across the globe because of unhealthy dietary habits, low physical activity and 
increasing incidence of obesity. However, in context to Nepal, few studies have been 
documented regarding the biochemical pa rameters of patients with NAFLD. Therefore, the 
present study, has tried to access the association of biochemical profiles with different grades of 
NAFLD estimating its risk with pre -existing co -morbid conditions.". Start with the novel 
findings. Next disc uss them in the setting of previosus studies. List the strengths and limitations 
of the study. Finally suggest a research agenda.  
 
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.  
 
Yes 
 
Are you able to as sess 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.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Not suitable for publication unless extensively edited  
 
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 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 understa nd 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:  Metabolic syndrome and biochemical changes among Non -Alcoholic Fatty Liver disease 
patients attending a tertiary c are hospital of Nepal  
 
Version: 0 Date: 15 Mar 2018 
 
Reviewer:  Amedeo  Lonardo  
 
Reviewer’s report:  
 
GENERAL COMMENT  
 
The amount of novel information is quite negligible. However, this study fills in a gap relative to 
the specific geographical area.  There are ser ious misconceptions regarding the relationship of 
NAFLD with the MetS, the diagnosis and pathogenesis of NAFLD and its association with 
raised liver enzymes. References are outdated and must be improved. English should carefully be 
edited.  
 
 
SPECIFIC COMMEN T 
 
This manuscript is not written in idiomatic English and must carefully be edited by a native 
English speaker/professional agency. There are several examples of sentences to be rephrase. 
Just to quote a few:  
 
"With a long history of discovery nearly 60 ye ars ago, nonalcoholic fatty liver disease (NAFLD)  
has emerged as the most common liver disease these days";  "NAFLD constitutes abnormal 
accumulation of fat in the liver without the considerable abuse of alcohol"; etc  
 
"NAFLD recognizable as the hepatic ma nifestation of metabolic syndrome" - and "Nowadays, 
NAFLD has been considered as hepatic compon ent of metabolic syndrome (MS)"  
 
 First: avoid repetiotions; Second and more important: this definitely is an outdated paradigm. 
Indeed NAFLD is mutually and bidi rectionally linked with MetS of which it is both the cause 
and the consequence (J Hepatol. 2018 Feb;68(2):335 -352.).  
 
 
mechanism of such  pathology is yet to be explored  
 
 Please, refer to more updated articles from the same group (e.g. Dig Liver Dis. 2017;49 :471-
483).  
 
 
"elevated transaminases and histo -pathological changes are well explained in NAFLD"  
 
- sentence unclear. Please rephrase.  
 
 
"Tan et al (9) suggested IDF criteria is applicable in an Asian population for risk assessment of 
MS 
 
while Pokharel et al  (10) suggests NCEP/ATP III to be specific for MS in our population but not  
applicable."  
 
- These Authors may be willing to explain what this statement has to do with the previous one 
""elevated transaminases and histo -pathological changes are well explaine d in NAFLD".  
 
 
"Liver biopsy remains the gold standard method for the diagnosis of hepatic steotosis and helps 
in exclusion from secondary etiology of liver injury"  
 
- These Authors may be wiiling to acknowledge that, histologically, NAFLD is 
indistinguishab le from Alcoholic liver disease.  
 
 
"The development of new inventions in the technology has given the alternatives to screen the 
patients without much of inconvenience like ultrasonography, computed tomography, magnetic 
resonance imaging, transient elastogr aphy. Due to cost -effectiveness and availability of 
ultrasonography, it is widely used to detect and grade NAFLD in our country"  
 
 Please, provide supporting references (e.g. Expert Rev Gastroenterol Hepatol. 2018;12:351 -
367) and briefly allude to the benef its of semi -quantitative US indices (Metabolism. 2017 
Jul;72:57 -65). 
 
 
"There is also an increase in the triglyceride and low density lipoprotein (LDL) level posing a  
cardiovascular risk (13)."  
 
 The mechanisms underlying excess cardiovascular risk in these NAFLD patients is much 
more complex than that and involves both generic mechanisms associated with the MetS and 
others specifically associated with NAFLD (J Hepatol. 2018 Feb;68(2):335 -352.; Nat Rev 
Endocrinol. 2018 Feb;14(2):99 -114).  
 
 
"Diagnosis of NAFLD  was made by abdominal ultrasonography."  
 
 This is a misconception which should be reworked. The diagnosis of NAFLD is based on 
imaging (fatty liver) IN THE ABSENCE OF COMPETING CAUSES OF STEATOSIS (J 
Hepatol. 2016;65:643 -4. J Hepatol. 2013;59:859 -71) . Ple ase, link this section with the next one 
(Inclusion/exclusion criteria) in order to avoid repetitions and misunderstandings.  
 
"Grading was done based on the standard criteria accepted by American, Gastroenterology 
Association."  
 
- Reference ?  
 
 
Patients with normal abdominal ultrasonography were categorized as control  
 
 Where these controls subjected to any lab. Assessment ?  
 
 
MMTH  
 
 Please, define when used for the first time.  
 
 
The study was carried out in Manmohan Memorial Teaching Hospital  
 
 the abbrieviation should be used here.  
 
 
all liver enzymes and lipid profile parameters showed significant statistical elevation  
among NAFLD patients.  
 
- The comment on liver enzymes results from the inclusion/exclusion criteria. In other words it 
mirrors the se lection done rather than being a findings.  
 
 
"non significant rise in creatinine and decrease in urea were observed among NAFLD patient" 
"furthermore, none of the hematological changes were significant in NAFLD and control 
population".  
 
 omit any comment on non-significant findings.  
 
 
The discussion should be reworked. Delete the following section "NAFLD, an appalling public 
health problem, is considered as one of the most common cause of liver disease, especially 
among obese and type 2 diabetic population (18 ) .The prevalence of NAFLD is constantly 
increasing across the globe because of unhealthy dietary habits, low physical activity and 
increasing incidence of obesity. However, in context to Nepal, few studies have been 
documented regarding the biochemical pa rameters of patients with NAFLD. Therefore, the 
present study, has tried to access the association of biochemical profiles with different grades of 
NAFLD estimating its risk with pre -existing co -morbid conditions.". Start with the novel 
findings. Next disc uss them in the setting of previosus studies. List the strengths and limitations 
of the study. Finally suggest a research agenda.  
 
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.  
 
Yes 
 
Are you able to as sess 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.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Not suitable for publication unless extensively edited  
 
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 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 understa nd 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:  Metabolic syndrome and biochemical changes among Non -Alcoholic Fatty Liver disease 
patients attending a tertiary c are hospital of Nepal  
 
Version: 0 Date: 15 Mar 2018 
 
Reviewer:  Amedeo  Lonardo  
 
Reviewer’s report:  
 
GENERAL COMMENT  
 
The amount of novel information is quite negligible. However, this study fills in a gap relative to 
the specific geographical area.  There are ser ious misconceptions regarding the relationship of 
NAFLD with the MetS, the diagnosis and pathogenesis of NAFLD and its association with 
raised liver enzymes. References are outdated and must be improved. English should carefully be 
edited.  
 
 
SPECIFIC COMMEN T 
 
This manuscript is not written in idiomatic English and must carefully be edited by a native 
English speaker/professional agency. There are several examples of sentences to be rephrase. 
Just to quote a few:  
 
"With a long history of discovery nearly 60 ye ars ago, nonalcoholic fatty liver disease (NAFLD)  
has emerged as the most common liver disease these days";  "NAFLD constitutes abnormal 
accumulation of fat in the liver without the considerable abuse of alcohol"; etc  
 
"NAFLD recognizable as the hepatic ma nifestation of metabolic syndrome" - and "Nowadays, 
NAFLD has been considered as hepatic compon ent of metabolic syndrome (MS)"  
 
 First: avoid repetiotions; Second and more important: this definitely is an outdated paradigm. 
Indeed NAFLD is mutually and bidi rectionally linked with MetS of which it is both the cause 
and the consequence (J Hepatol. 2018 Feb;68(2):335 -352.).  
 
 
mechanism of such  pathology is yet to be explored  
 
 Please, refer to more updated articles from the same group (e.g. Dig Liver Dis. 2017;49 :471-
483).  
 
 
"elevated transaminases and histo -pathological changes are well explained in NAFLD"  
 
- sentence unclear. Please rephrase.  
 
 
"Tan et al (9) suggested IDF criteria is applicable in an Asian population for risk assessment of 
MS 
 
while Pokharel et al  (10) suggests NCEP/ATP III to be specific for MS in our population but not  
applicable."  
 
- These Authors may be willing to explain what this statement has to do with the previous one 
""elevated transaminases and histo -pathological changes are well explaine d in NAFLD".  
 
 
"Liver biopsy remains the gold standard method for the diagnosis of hepatic steotosis and helps 
in exclusion from secondary etiology of liver injury"  
 
- These Authors may be wiiling to acknowledge that, histologically, NAFLD is 
indistinguishab le from Alcoholic liver disease.  
 
 
"The development of new inventions in the technology has given the alternatives to screen the 
patients without much of inconvenience like ultrasonography, computed tomography, magnetic 
resonance imaging, transient elastogr aphy. Due to cost -effectiveness and availability of 
ultrasonography, it is widely used to detect and grade NAFLD in our country"  
 
 Please, provide supporting references (e.g. Expert Rev Gastroenterol Hepatol. 2018;12:351 -
367) and briefly allude to the benef its of semi -quantitative US indices (Metabolism. 2017 
Jul;72:57 -65). 
 
 
"There is also an increase in the triglyceride and low density lipoprotein (LDL) level posing a  
cardiovascular risk (13)."  
 
 The mechanisms underlying excess cardiovascular risk in these NAFLD patients is much 
more complex than that and involves both generic mechanisms associated with the MetS and 
others specifically associated with NAFLD (J Hepatol. 2018 Feb;68(2):335 -352.; Nat Rev 
Endocrinol. 2018 Feb;14(2):99 -114).  
 
 
"Diagnosis of NAFLD  was made by abdominal ultrasonography."  
 
 This is a misconception which should be reworked. The diagnosis of NAFLD is based on 
imaging (fatty liver) IN THE ABSENCE OF COMPETING CAUSES OF STEATOSIS (J 
Hepatol. 2016;65:643 -4. J Hepatol. 2013;59:859 -71) . Ple ase, link this section with the next one 
(Inclusion/exclusion criteria) in order to avoid repetitions and misunderstandings.  
 
"Grading was done based on the standard criteria accepted by American, Gastroenterology 
Association."  
 
- Reference ?  
 
 
Patients with normal abdominal ultrasonography were categorized as control  
 
 Where these controls subjected to any lab. Assessment ?  
 
 
MMTH  
 
 Please, define when used for the first time.  
 
 
The study was carried out in Manmohan Memorial Teaching Hospital  
 
 the abbrieviation should be used here.  
 
 
all liver enzymes and lipid profile parameters showed significant statistical elevation  
among NAFLD patients.  
 
- The comment on liver enzymes results from the inclusion/exclusion criteria. In other words it 
mirrors the se lection done rather than being a findings.  
 
 
"non significant rise in creatinine and decrease in urea were observed among NAFLD patient" 
"furthermore, none of the hematological changes were significant in NAFLD and control 
population".  
 
 omit any comment on non-significant findings.  
 
 
The discussion should be reworked. Delete the following section "NAFLD, an appalling public 
health problem, is considered as one of the most common cause of liver disease, especially 
among obese and type 2 diabetic population (18 ) .The prevalence of NAFLD is constantly 
increasing across the globe because of unhealthy dietary habits, low physical activity and 
increasing incidence of obesity. However, in context to Nepal, few studies have been 
documented regarding the biochemical pa rameters of patients with NAFLD. Therefore, the 
present study, has tried to access the association of biochemical profiles with different grades of 
NAFLD estimating its risk with pre -existing co -morbid conditions.". Start with the novel 
findings. Next disc uss them in the setting of previosus studies. List the strengths and limitations 
of the study. Finally suggest a research agenda.  
 
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.  
 
Yes 
 
Are you able to as sess 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.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Not suitable for publication unless extensively edited  
 
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 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 understa nd 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