Review for 10.1186/s12876-021-01790-w (2021)

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. 
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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