Reviewer’s report
Title: 
Normalization of 
γ
-glutamyl transferase levels is associated with better metabolic control in
individuals with nonalcoholic fatty liver disease
Version: 
0 
Date: 
20 Dec 2020
Reviewer's report:
Here, the authors investigated change in ALT in AST levels in their NAFLD group after receiving medical
consulting and treatment. They recommended that GGT may be more helpful compared to ALT in follow-
up and monitoring the treatment response in those patients. In my opinion, their work is not very well
written which makes the understanding difficult. Therefore, in this form their study is not appropriate for
publication. 
However, the authors can benefit greatly from my comments for improving their work. 
1. I recommend editing the language.
2. In introduction, the authors defined MAFLD and NAFLD identically. However, MAFLD is defined
with positive criteria rather than exclusion of secondary causes of hepatic fat accumulation (J Hepatol.
2020 Jul;73(1):202-209). This change in nomenclature proposes a better understanding of the disease
etiology, however its use is still not very expanded (Expert Rev Gastroenterol Hepatol. 2020 Dec 9:1-8.
doi: 10.1080/17474124.2021.1860019. Online ahead of print, Hepatology Forum 2020; 3(1): 79-81). I
recommend defining MALD and referring to that issue citing the references here. 
3. In abstract and also in methods, the authors stated this study as retrospective. However, apparently they
conducted their study prospectively, as they stated in discussion. All in all the authors did not well defined
how they conducted the study. Unfortunately, that creates confusion for the readers. Please eliminate this
issue.
4. Unfortunately, there is some unclearness in methods. 
"The diagnosis of NAFLD was defined as (1) liver
histology or imaging (such as abdominal ultrasonography or Magnetic resonance imaging-based proton
density fat fraction (MRI-PDFF) manifesting liver steatosis; (2) no drinking history or previous history of
alcohol consumption < 140 g/week in men or < 70 g/week in women; (3) no history of drug induced liver
disease, total parenteral nutrition, hepatolenticular degeneration, autoimmune hepatitis and other specific
diseases that may lead to fatty liver [11]." It seems like the authors did not perform liver biopsy. Therefore,
I suggest removing liver biopsy from methodology. That issue is also present in the discussion. The
authors stated that they did not perform liver biopsy in all the patients. However, they defined hepatic
steatosis according to ultrasonography in all the patients. Therefore, please also consider explaining the
hepatic steatosis criteria according to ultrasonography. Obviously, the authors also conducted MRI-PDFF.
Why authors did not choose to include a homogenous definition of hepatic steatosis according to a single
imaging methodology?
5. The authors were followed-up in 12 months and in some patients the authors conducted MRI-PDFF. In
how many patients? Why did the authors conduct follow-up MRI-PDFF in only some patients? 
6. The authors did not make a definition of normalization of ALT and GGT. Was this defined as
normalization according to the laboratory cut-off? Please eliminate this issue.
7. The authors included in their research 4 groups as abnormal ALT and GGT, only abnormal ALT, only
abnormal GGT, normalization of both ALT-GGT. I guess, the authors meant both normal ALT and GGT. 
8. It is well known, that statin use and antidiabetic medication were associated with the normalization of
enzyme levels (J Clin Exp Hepatol. 2019 Nov-Dec; 9(6): 723-730.). Therefore, the authors should state
the distribution of types of antidiabetic drugs and statins prescribed to their population and discuss the
effects of those to the enzyme normalization.
9. Enzyme levels were not an accurate predictor of liver fibrosis which is the most important predictor of
prognosis. Previously, it has been shown that patients with both normal and abnormal transaminase levels
showed similar advanced fibrosis prevalence (J Gastrointestin Liver Dis. 2019 Dec 9;28(4):427-431).
However, recently it is proposed that patients with consistently normal ALT levels are at reduced risk for
cirrhosis (Hepatology. 2020 Oct;72(4):1242-1252.). It is appropriate to discuss this issue referring to
these references. 
Publons Reviewer Recognition
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published on its webservice if you have registered for such service or help editors to identify candidate
reviewers. Please find the details of processing in Publons’ privacy policy
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Yes
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.
I declare that I have no competing interests
Reviewer Publication Consent.
 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
) if this manuscript is
accepted for publication. Any comments that I do not wish to be included in the published report have
been included as confidential comments to the editor, which will not be published.
If you are not happy
for us to publish this report, please contact the editorial office before completing the review.
If you
wish, you can include your name in your published report. Please note you must decide whether to
include your name at the start of the process and confirm this decision whenever prompted. If you
change your decision later, we will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name with my report. (default)
Is the study design appropriate to answer the research question (including the use of appropriate controls),
and are the conclusions supported by the evidence presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free from apparent
manipulation?
Yes
Reviewer’s report
Title: 
Normalization of 
γ
-glutamyl transferase levels is associated with better metabolic control in
individuals with nonalcoholic fatty liver disease
Version: 
0 
Date: 
20 Dec 2020
Reviewer's report:
Here, the authors investigated change in ALT in AST levels in their NAFLD group after receiving medical
consulting and treatment. They recommended that GGT may be more helpful compared to ALT in follow-
up and monitoring the treatment response in those patients. In my opinion, their work is not very well
written which makes the understanding difficult. Therefore, in this form their study is not appropriate for
publication. 
However, the authors can benefit greatly from my comments for improving their work. 
1. I recommend editing the language.
2. In introduction, the authors defined MAFLD and NAFLD identically. However, MAFLD is defined
with positive criteria rather than exclusion of secondary causes of hepatic fat accumulation (J Hepatol.
2020 Jul;73(1):202-209). This change in nomenclature proposes a better understanding of the disease
etiology, however its use is still not very expanded (Expert Rev Gastroenterol Hepatol. 2020 Dec 9:1-8.
doi: 10.1080/17474124.2021.1860019. Online ahead of print, Hepatology Forum 2020; 3(1): 79-81). I
recommend defining MALD and referring to that issue citing the references here. 
3. In abstract and also in methods, the authors stated this study as retrospective. However, apparently they
conducted their study prospectively, as they stated in discussion. All in all the authors did not well defined
how they conducted the study. Unfortunately, that creates confusion for the readers. Please eliminate this
issue.
4. Unfortunately, there is some unclearness in methods. 
"The diagnosis of NAFLD was defined as (1) liver
histology or imaging (such as abdominal ultrasonography or Magnetic resonance imaging-based proton
density fat fraction (MRI-PDFF) manifesting liver steatosis; (2) no drinking history or previous history of
alcohol consumption < 140 g/week in men or < 70 g/week in women; (3) no history of drug induced liver
disease, total parenteral nutrition, hepatolenticular degeneration, autoimmune hepatitis and other specific
diseases that may lead to fatty liver [11]." It seems like the authors did not perform liver biopsy. Therefore,
I suggest removing liver biopsy from methodology. That issue is also present in the discussion. The
authors stated that they did not perform liver biopsy in all the patients. However, they defined hepatic
steatosis according to ultrasonography in all the patients. Therefore, please also consider explaining the
hepatic steatosis criteria according to ultrasonography. Obviously, the authors also conducted MRI-PDFF.
Why authors did not choose to include a homogenous definition of hepatic steatosis according to a single
imaging methodology?
5. The authors were followed-up in 12 months and in some patients the authors conducted MRI-PDFF. In
how many patients? Why did the authors conduct follow-up MRI-PDFF in only some patients? 
6. The authors did not make a definition of normalization of ALT and GGT. Was this defined as
normalization according to the laboratory cut-off? Please eliminate this issue.
7. The authors included in their research 4 groups as abnormal ALT and GGT, only abnormal ALT, only
abnormal GGT, normalization of both ALT-GGT. I guess, the authors meant both normal ALT and GGT. 
8. It is well known, that statin use and antidiabetic medication were associated with the normalization of
enzyme levels (J Clin Exp Hepatol. 2019 Nov-Dec; 9(6): 723-730.). Therefore, the authors should state
the distribution of types of antidiabetic drugs and statins prescribed to their population and discuss the
effects of those to the enzyme normalization.
9. Enzyme levels were not an accurate predictor of liver fibrosis which is the most important predictor of
prognosis. Previously, it has been shown that patients with both normal and abnormal transaminase levels
showed similar advanced fibrosis prevalence (J Gastrointestin Liver Dis. 2019 Dec 9;28(4):427-431).
However, recently it is proposed that patients with consistently normal ALT levels are at reduced risk for
cirrhosis (Hepatology. 2020 Oct;72(4):1242-1252.). It is appropriate to discuss this issue referring to
these references. 
Publons Reviewer Recognition
. Springer Nature can send verification of this review directly to Publons
(a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on
the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted to Publons after the final
decision on the manuscript has been made. If you have already registered at Publons, they will notify you
of the receipt of this review and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to register in order for them to
be able to recognize your review on your new profile page. Publons may use the Review Data to generate
derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity
of such information. For example, Publons may verify your record as a reviewer by updating your profile
published on its webservice if you have registered for such service or help editors to identify candidate
reviewers. Please find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
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.
I declare that I have no competing interests
Reviewer Publication Consent.
 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
) if this manuscript is
accepted for publication. Any comments that I do not wish to be included in the published report have
been included as confidential comments to the editor, which will not be published.
If you are not happy
for us to publish this report, please contact the editorial office before completing the review.
If you
wish, you can include your name in your published report. Please note you must decide whether to
include your name at the start of the process and confirm this decision whenever prompted. If you
change your decision later, we will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name with my report. (default)
Is the study design appropriate to answer the research question (including the use of appropriate controls),
and are the conclusions supported by the evidence presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free from apparent
manipulation?
Yes
Please review this paper.
user
Reviewer’s report
Title: 
Normalization of 
γ
-glutamyl transferase levels is associated with better metabolic control in
individuals with nonalcoholic fatty liver disease
Version: 
0 
Date: 
20 Dec 2020
Reviewer's report:
Here, the authors investigated change in ALT in AST levels in their NAFLD group after receiving medical
consulting and treatment. They recommended that GGT may be more helpful compared to ALT in follow-
up and monitoring the treatment response in those patients. In my opinion, their work is not very well
written which makes the understanding difficult. Therefore, in this form their study is not appropriate for
publication. 
However, the authors can benefit greatly from my comments for improving their work. 
1. I recommend editing the language.
2. In introduction, the authors defined MAFLD and NAFLD identically. However, MAFLD is defined
with positive criteria rather than exclusion of secondary causes of hepatic fat accumulation (J Hepatol.
2020 Jul;73(1):202-209). This change in nomenclature proposes a better understanding of the disease
etiology, however its use is still not very expanded (Expert Rev Gastroenterol Hepatol. 2020 Dec 9:1-8.
doi: 10.1080/17474124.2021.1860019. Online ahead of print, Hepatology Forum 2020; 3(1): 79-81). I
recommend defining MALD and referring to that issue citing the references here. 
3. In abstract and also in methods, the authors stated this study as retrospective. However, apparently they
conducted their study prospectively, as they stated in discussion. All in all the authors did not well defined
how they conducted the study. Unfortunately, that creates confusion for the readers. Please eliminate this
issue.
4. Unfortunately, there is some unclearness in methods. 
"The diagnosis of NAFLD was defined as (1) liver
histology or imaging (such as abdominal ultrasonography or Magnetic resonance imaging-based proton
density fat fraction (MRI-PDFF) manifesting liver steatosis; (2) no drinking history or previous history of
alcohol consumption < 140 g/week in men or < 70 g/week in women; (3) no history of drug induced liver
disease, total parenteral nutrition, hepatolenticular degeneration, autoimmune hepatitis and other specific
diseases that may lead to fatty liver [11]." It seems like the authors did not perform liver biopsy. Therefore,
I suggest removing liver biopsy from methodology. That issue is also present in the discussion. The
authors stated that they did not perform liver biopsy in all the patients. However, they defined hepatic
steatosis according to ultrasonography in all the patients. Therefore, please also consider explaining the
hepatic steatosis criteria according to ultrasonography. Obviously, the authors also conducted MRI-PDFF.
Why authors did not choose to include a homogenous definition of hepatic steatosis according to a single
imaging methodology?
5. The authors were followed-up in 12 months and in some patients the authors conducted MRI-PDFF. In
how many patients? Why did the authors conduct follow-up MRI-PDFF in only some patients? 
6. The authors did not make a definition of normalization of ALT and GGT. Was this defined as
normalization according to the laboratory cut-off? Please eliminate this issue.
7. The authors included in their research 4 groups as abnormal ALT and GGT, only abnormal ALT, only
abnormal GGT, normalization of both ALT-GGT. I guess, the authors meant both normal ALT and GGT. 
8. It is well known, that statin use and antidiabetic medication were associated with the normalization of
enzyme levels (J Clin Exp Hepatol. 2019 Nov-Dec; 9(6): 723-730.). Therefore, the authors should state
the distribution of types of antidiabetic drugs and statins prescribed to their population and discuss the
effects of those to the enzyme normalization.
9. Enzyme levels were not an accurate predictor of liver fibrosis which is the most important predictor of
prognosis. Previously, it has been shown that patients with both normal and abnormal transaminase levels
showed similar advanced fibrosis prevalence (J Gastrointestin Liver Dis. 2019 Dec 9;28(4):427-431).
However, recently it is proposed that patients with consistently normal ALT levels are at reduced risk for
cirrhosis (Hepatology. 2020 Oct;72(4):1242-1252.). It is appropriate to discuss this issue referring to
these references. 
Publons Reviewer Recognition
. Springer Nature can send verification of this review directly to Publons
(a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on
the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted to Publons after the final
decision on the manuscript has been made. If you have already registered at Publons, they will notify you
of the receipt of this review and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to register in order for them to
be able to recognize your review on your new profile page. Publons may use the Review Data to generate
derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity
of such information. For example, Publons may verify your record as a reviewer by updating your profile
published on its webservice if you have registered for such service or help editors to identify candidate
reviewers. Please find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
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.
I declare that I have no competing interests
Reviewer Publication Consent.
 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
) if this manuscript is
accepted for publication. Any comments that I do not wish to be included in the published report have
been included as confidential comments to the editor, which will not be published.
If you are not happy
for us to publish this report, please contact the editorial office before completing the review.
If you
wish, you can include your name in your published report. Please note you must decide whether to
include your name at the start of the process and confirm this decision whenever prompted. If you
change your decision later, we will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name with my report. (default)
Is the study design appropriate to answer the research question (including the use of appropriate controls),
and are the conclusions supported by the evidence presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free from apparent
manipulation?
Yes
assistant