Is HSD17B13 Genetic Variant a Protector for Liver Dysfunction? Future Perspective as a Potential Therapeutic Target
, Ricardo Diaz-Aragon 1, Lanuza A. P. Faccioli 1, Michelle R. Malizio 1, Michael C. Coard 1, Zehra N. Kocas-Kilicarslan 1, Carla Frau 1, Nils Haep 1, Alina Ostrowska 1,2, Rodrigo M. Florentino 1,* and Alejandro Soto-Gutierrez 1,2,3,*
Round 1
Reviewer 1 Report
The authors reviewed the potential risk factors and discussed evidence about a potential therapeutic target in treating FLD. The paper is easy to follow, it has a logical flow and provides an advance in the field.
Author Response
We are thankful to reviewers 1 and 2 for their valuable time reading our manuscript.
Reviewer 2 Report
The work of Mr Takashi Motomura et al consists of the role of HSD17B13 Genetic Variant as a potential protector for liver dysfunction.
It is a comprehensive well structered and well written manucript with many novelties that merit publication
Author Response
We are thankful to reviewers 1 and 2 for their valuable time reading our manuscript.
Reviewer 3 Report
Motomura/Amirneni and co-workers offer an interesting and stimulating overview on the role of one of the 17β-HSD family member (HSD17B13) in liver disorders, with particular interest in fatty liver diseases. Genome-wide association studies (GWAS) have contributed greatly to pathophysiology and prognosis of NAFLD during the past years.
The authors describe and analyze current literature on HSD17B13 and different genetic variants in the context of NALFD and viral hepatitis or hepatocellular carcinoma. The authors summarized state-of-the-art evidence as well as they pose important questions and hypothesis on the role of this prognostic marker in the context of hepatic pathogenesis. The manuscript is eloquent and has scientific rigor, however an additional revision is strongly recommended, to edit/remove repetitions and redundancies, or speculations which should be put in the context of current preclinical/clinical approaches. A table summarizing and collecting all the variants identified so far and mentioned in the text would be definitely beneficial for the reader.
Furthermore, the authors correctly reported the studies offered by Abul-Husn and coll. or Ma Y and coll. However, I was not able to find any mention for the seminal GWAS report confirming association between HSD17B13 SNP and ALT levels, in correlation with NAFLD (Chambers JC, et al. Nat Genet 2011; 43: 1131).
Similarly, we would like to suggest mentioning and including the GWAS study performed on a cohort of pediatric and adult patients recently offered by Namjou and coll., where the authors confirmationed NAFLD risk locus and several novel associations (including HSD17B13; Namjou B, et al. BMC Med 2019; 17 (135))
Author Response
We appreciate the comments. We have added the two suggested studies in our text and included in the table all of the variants mentioned in the text. We also believe that this modification will help future readers. After all of the modifications, the text was carefully read to eliminate repetitions, redundancies, and speculations, as suggested by this reviewer. The changes in the main text were highlighted.
