Review for 10.1186/s12876-021-02067-y (2021)

Reviewer’s report
Title: 
Association of HSD17B13 rs72613567: TA allelic variant with liver
disease: review and meta-analysis
Version: 
1 
Date: 
14 Jul 2021
Reviewer: 
Citrawati Dyah Kencono Wungu
Reviewer's report:
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This manuscript studied the association of HSD17B13 rs72613567: TA allelic
variant with liver disease. THe topic is actually pretty interesting; however, there
are some major concerns that 
should be fixed:
1. There has been a similar meta-analysis before (with more detailed
explanation): 10.26355/eurrev_202009_22842. Please highlight the novelty of
this current paper to raise its interest for the readers.
2. OR less than 1 means that it has lower risk. In this study, it means TA allelic
variant will decrease the risk of HCC (OR=0.766 and 0.649), or protective
against HCC, not the opposite. Thus, there has been a major misinterpretation
here, as the authors stated that HSD17B13 rs7261356:TA allelic variant was
associated with HCC risk.
3. The term CLD here should be specified, as HCC itself should have been part
of CLD. Is it chronic hepatitis, liver cirrhosis, or what condition?
4. The article is lacking explanation regarding HSD17B13 rs7261356:TA allelic
variant itself. Please describe the gene, polymorphism type, and its role and how
it is related to liver disease.
Where is its location in gene(intron/exon, number)? How about its mechanism?
What is the role of the protein? How many alleles does it have?
5. In the inclusion criteria, CLD, HCC, NAFLD, and AFLD definitions and
diagnosis criteria should be added. Language restriction, duplication, and age
limitation of the participants should also be added. It is also mentioned in the
inclusion criteria: "if two (or more) studies included the same cohort..." Whereas
all of the included studies were case control.
6. There is no risk of bias assessment in this manuscript, in which it is a
compulsory thing that should be performed in a systematic review/meta-analysis.
7. Many important informastion are not presented in the table of study
characteristic, for example:(1) Matching variables/adjustment of confounding
factors; (2) mean age of the participants; (3) The presence of hepatitis virus
infection or other HCC etiology/risk factors; (4) What does non NAFLD here
means? Is it any liver disease other NAFLD or ALD? 
8. There should be at least two genetic model analysis for this polymorphism:
additive and allelic model, while in this study, only 1 model was performed.
9. The discussion is so lacking. The mechanism of rs7261356:TA allelic variant
to HSD17B13 protein and how it affects HCC should be explained molecularly.
Explain also the metabolism involved on HCC and NAFLD.
10. How does the result connect with the existing theories? How is the result of
the current study compared to previous studies? Benefit and future prospectives?
11. Why did the authors only include case control but not cohort study type? 
12. More limitation of this study should be added, for example: this study only
included case control. Besides, there are also many confounding factors which
contribute to HCC and NAFLD, e.g. other polymorphisms, smoking, alcohol,
age, gender, hepatitis virus infection, etc
13. As the discussion is lacking, we also suggest the authors to read and add
more references to the studies.
There are also some minor comments:
1. The number of included studies should be written in words, not number. For
example, it should be "five studies", instead of "5 studies"
2. There are some grammatical errors that should be fixed. The author should
proofread the manuscript.
3. In the exclusion criteria, it is stated: "no-case-control study". Does it mean
studies other than case control study design?
4. Describe the developer of the software used.
5. In Table 1, Europe is a continent, not country. Please mention the specific
countries
6. There is no citation of Stickel.F 2019 in Table 1.
7. Hardy-Weinberg equilibrium test should be performed.
8. In Table 2, please describe the number of studies in each group.
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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?
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Are the methods sufficiently described to allow the study to be repeated?
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Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
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