Review for 10.1186/s12876-021-01688-7 (2021)

Reviewer’s report
Title: 
Association of meat consumption with NAFLD risk and liver-related
biochemical indexes in older Chinese: a cross-sectional study
Version: 
1 
Date: 
01 Nov 2020
Reviewer's report:
Major comments:
R1. A part from the well-known explanation of the authors regarding the
highlighted concern and the wise decision to clarify it in the introduction section,
the absence of a sufficient proportion of young patients in the study population
doesn't consist in an advantage for the assessment of the role of a specific risk
factor in inducing the disease. This is independent of the very well and careful
highlighted knowledge of the scientific literature regarding EPIDEMIOLOGIC
data.
It is necessary to insert the concept in the study limitations.
R2: the authors properly addressed my comment
R3: The authors addressed my request regarding the lack of thyroid data.
However, the highlighted concern regarding the possible interference of the
medication assumed by the study population on the showed results still need a
clarification (eg. antidiabetic drugs?, herbal products? What does "diet pills"
mean?).
R4: This represents a crucial point of the peer reviewing process of this paper. I
suppose it is necessary a clarification: of course, it is not possible to suggest to
perform the biopsy to the entire NAFLD population for the properly mentioned
motivations. However, the ultrasound examination, also in case it would be
performed by expert physicians, didn't have a strong sensibility in the
identification of low-degree of steatosis, and, independently of this last point, it
doesn't give to the researcher/physician an "analytic quantitative measure" of the
steatosis degree. My comment was not related to criticize the use of the
ultrasound examination as optimal screening procedure for the steatosis detection
(considering anyway the just mentioned comment about the low-degree steatosis
power of detection) but, for the study purpose, the use of a steatosis degree
assessment (in a non-invasive way of course) as well as fibrosis degree (see the
following part of the reply) would have given to the paper a very strong
improvement.
Moreover, passing to the staging of the disease, it is absolutely unquestionable
the power of the ultrasound examination in the identification of advanced forms
of liver disease, but, one more time, the technique doesn't meet the
"quantification criteria", being only able to differentiate between not-severe and
severe disease. So now, I don't agree with some sentences in the answer of the
authors (independently from the fact that I have never recommended them the
use of liver biopsy in this context):
- "However, its invasive nature, high cost and inter and intra-observer variability
make it less suitable for diagnosis and disease monitoring in clinical practice,
and unsuitable for screening at a population level" - the intra observer variability
in an experimental context (because we are talking about this) could be resolved
by the use of a centralized histology analysis, and, as extensively explained
before: no one recommended the use of the biopsy for liver steatosis screening. 
- "(MRI) was more accuracy than ultrasonography examination, its high costs
and a long time of execution, make the procedure not recommended in the daily
clinical setting." - I agree with the cost analysis (in part, because it must be
considered the advantage that it could be possible to obtain by the use of this
technique, I undescribed one more time: IN AN EXPERIMENTAL CONTEXT).
However, it is necessary to bear in mind that for this purpose it is possible to
conduct a MRI examination limited to the liver (as properly did in other
experimental projects): it takes not more time than an abdominal ultrasound
examination.
- "A metanalysis reported that compared to histology, ultrasonography can
reliably and
accurately detect moderate-severe fatty liver, with an overall sensitivity of 84.8%
(95%
confidence interval [CI]: 79.5-88.9) and specificity of 93.6% (87.2-97.0)". -
precisely, moderate-severe fatty liver, see the previous comments. Hepatology.
2011;54:1082-90. PMID: 21618575: precisely, moderate-severe fatty liver, see
the previous comments. 
The authors included in the study limitations some comments about this point,
even if I don't still agree with the sentence "Hence, an investigative bias may
exist but it is not likely to have a significant impact". 
It remains to address the second part of the comment that could give to the paper
a significant improvement: the lack of the use of non-invasive scores of
fibrosis/steatosis.
R5: It remains a strong study limitation. I think it is not enough to resolve the
concern with the sentences 101-105. In case of understandable not applicability
of a computerized food analysis, this concern would be at least largely addressed
in the discussion/study limitations section.
R6: a part the previously highlighted concern about the medications, the authors
answered properly to my comments.
R7: the concern is still pending: "…and didn't use any strategy for the steatosis
severity assessment" 
Minor comments:
R1: the authors answered properly to my comment
R2: "We have used "liver-related biochemical indexes" instead of "liver related
biomarkers". It is basically the same. Please define which biomarkers have you
assessed.
R3: the authors answered properly to my comment
R4: the authors answered properly to my comment
R5: the authors answered properly to my comment
R6: the authors answered properly to my comment
R7: the authors answered properly to my comment
R8: the authors answered properly to my comment
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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?
No
Are the methods sufficiently described to allow the study to be repeated?
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from apparent manipulation?
Yes