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: 
06 Nov 2021
Reviewer's report:
In this meta-analysis article Thang et al. correlate the HSD17B13 allelic variant
rs72611356:TA with liver disease (HCC, NAFLD, and non-NAFLD). 
Even though the idea of performing an association study correlating the
HSD17B13 variant with liver disease in a big cohort of patients could potentially
provide sophisticated knowledge, I have some major remarks.
Major comments:
1) 1) The statistical analysis has been performed correlating the incidence of the
rs72611356:TA allelic variant in HCC compared with chronic liver disease first,
and with healthy controls afterward. Moreover, to evaluate the association of the
variant with NAFLD, Thang et al. performed a similar analysis by comparing
NAFLD with non-NAFLD patients.
To evaluate the impact of the variant on the risk of NAFLD it would be more
appropriate to perform a correlation between NAFLD vs healthy controls. I
suggest to perform this type of analysis if possible.
2) In the paragraph Association between HSD17B13 rs7261356: TA allelic
variant and NAFLD is not clear how the comparison has been performed also in
relationship with the associated figure 4. From the manuscript: Using random-
effect model, we found no significant association between the HSD17B13
rs7261356: TA allelic variant and NAFLD:TA vs T OR=0.749, 95% CI=0.517-
1.804, P=0.126 (lines 14-19 
and figure 4).
3) In the paragraph Sensitivity analysis and publication bias is mentioned that
sensitivity analysis showed that no single study impacted the overall ORs
qualitatively (line 15-18). However, in figure 2 the overall result looks to be
strongly affected by the weight of the Stickel F study compared to the other four
studies selected. Please justify this incongruence.
4) 
In the same paragraph mentioned in point 3 (lines 21-23), authors write: The
Egger regression analysis suggested that obviously publication bias existed in
HCC patients compared with healthy controls. 
Egger's method is applicable when a high number of studies are considered. Its
power is low when few studies are evaluated. I don't think that this represents the
appropriate method for biases evaluation.
Minor comments: 
In the section Discussion (lines 5-8) is better to precise that the differences in
species could be responsible for the contradictory results.
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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?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes