Review for 10.1186/s12876-019-1149-z (2019)

Reviewer’s report
Title: Validity of biopsy-based drug effects in a diet-induced obese mouse model of biopsyconfirmed
NASH
Version: 0 Date: 13 Aug 2019
Reviewer: Nakade Yukiomi
Reviewer's report:
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The authors showed that stereological validation of biopsy-based histopathology assessment of drug
treatment effects in a diet-induced obese mouse model of biopsy-confirmed NASH. The purpose of this
study is to examine how well biopsy-based quantitative image analyses correlate to stereology-based
whole-liver quantitative changes upon drug treatment. The authors concluded that an in-depth analyses
of  liver  homogeneity  demonstrated  that  drug  induced  improvement  in  liver  biopsy-assessed
histopathology is representative for overall liver effects assessed using stereology. Unfortunately, this
paper is very difficult to read. Therefore, it describes the evaluation of histological heterogeneity in the
liver in NASH and the comparison of the effects of the three drugs against it, but this is very difficult to
understand. In particular, the discussion section is very difficult to understand, so it is recommended to
rebuild it.
Major comments
GLP-1 agonist, INT-767, elafibronor are used in the pharmacotherapy intervention for NASH. The
reason why these drugs were used should be given. There is no explanation of these drugs in the
introduction or abstract, so it should be mentioned first. And please explain how the effectiveness of
these drugs against NASH is compared with past experiments.
Inflammation  is  assessed  by  Gal-3  and  fibrosis  assessment  by  col1A1,  but  why  did  other
immunohistological markers not be adopted? What was the actual inflammatory cell infiltration and
liver fibrosis? I think that it should be evaluated by SAF score (Beodssa et al, Hepatology, 2014) and
not NAS.。
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
No
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 assess 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:
Needs some language corrections before being published
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