Review for 10.1186/s12876-021-01601-2 (2021)

Reviewer’s report
Title: 
Factors associated with elevated alanine aminotransferase in employees of
a German chemical company: results of a large cross-sectional study
Version: 
1 
Date: 
04 Dec 2020
Reviewer's report:
In their study, the authors investigated the prevalence of elevated alanine
transaminase levels in a large group of employees working in a chemical
company in Germany showing the association of elevated ALT with
demographic and lifestyle characteristics. Owing to the large sample of the
group, their work provides significant knowledge to the current literature of
occupational medicine. However, I recommend taking my comments into
consideration for the sake of clarifying some issues.
1. The significant alcohol use was defined as a daily alcohol consumption >21
standard drinks per week in men and >14 standard drinks per week in women.
According to the AASLD guideline, for the diagnosis of NAFLD a significant
alcohol consumption must be excluded (Hepatology. 2018;67:328-357). Here,
participants with a history of alcohol abuse were excluded from study. However,
there are participants consuming more than 3 drinks per week. Did the authors
also exclude the significant alcohol consumption? 
2. Moreover, the exclusion criteria are not clearly described in methods. Did the
authors exclude presence of any chronic liver disease, use of steatogenic
medications, pregnancy, substance abuse etc.?
3. Obesity "class" is a more accurate terminology compared to obesity "type"
according to classification of WHO. 
4. I suggest discussing the potential influence of hepatotoxic materials to their
cohorts in the study. 
Apparently, the hepatotoxicity is negligible due to strict
safety rules. 
However, it is appropriate to mention this in their study in terms of
clarifying the working conditions of the study population. 
5. Previously, many studies aimed to find the optimal upper limit of ALT for
healthy individuals. Based on the ethnicity and study characteristics different
cut-offs are recommended (Hepatology Forum 2020; 2(1): 44-47; Hepatology
2012;55(2):447-454; Hepatology 2010;51(5):1577-1583.) Here, the laboratory-
specific upper limit of normal ALT activity was accepted as 45 U/L for males
and 34 U/L for females. Are these cut-offs acceptable in their study population?
Please discuss this referring to the recent studies I recommend here. 
6. In NAFLD, liver fibrosis is the most important prognostic factor. As also
recommended in the major guidelines, FIB-4 and NFS are useful diagnostic
modalities in estimation of advanced fibrosis (Hepatology. 2018;67:328-357.; J
Hepatol. 2016 Jun;64(6):1388-402). They show also acceptable diagnostic
performance both in patients with elevated and normal transaminase levels. FIB-
4 can be used over NFS owing to its ease of calculation due to including fewer
parameters (Hepatology Forum 2020; 1(1): 8-13). Please refer to this issue citing
the references I recommend. 
I also recommend calculating et least FIB-4 for
those participants with a possible diagnosis of NAFLD according to elevated
ALT levels and present them as low, indeterminate and high risk of advanced
fibrosis for the sake of applying risk stratification. 
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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
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Yes
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Yes
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from apparent manipulation?
Yes