Title: Relationship of circulating total bilirubin, UDP-glucuronosyltransferases 1A1 and the
development of non-alcoholic fatty liver disease: a cross-sectional study
Version: 2 Date: 07 Oct 2021
Reviewer's report:
Comments to the Author
In this study, the authors investigated the association between circulating TB /UGT1A1 and
liver fat fraction. Hepatic steatosis severity examined by MRI-PDFF was valuable and focusing
UGT1A1 besides total bilirubin was the novelty of this study. However, there is a lack of
assessment to understand the mechanism of the positive correlation of TB/UGT1A1 with fat
fraction. I have some comments and queries:
Major
1) The authors investigated circulating UGT1A1 and found correlation with fat fraction in the
NAFLD patients with severe steatosis. While the function of UGT1A1 in liver tissue especially
regarding gene variants has been well discussed so far, the meaning of calculating UGT1A1 in
blood is not elucidated. Are there any previous studies which looked at the circulating UGT1A1?
The authors should discuss the mechanism underlying elevated amount of UGT1A1 in blood.
2) Although a fair amount of previous study showed that serum bilirubin levels are inversely
associated with development of NAFLD/NASH as the authors described, this study found TB
was higher in the patients with moderate and severe steatosis. I suggest the author discuss why
the present study showed the different result from the previous reports which showed inversely
association between TB and NAFLD. In addition, investigating direct bilirubin and indirect
bilirubin would be valuable especially discussing the relation with UGT1A1 in this study.
3) The author presented cutoff value of TB and UGT1A1 on NAFLD. However, AUROC was
very low and predictive power is too weak to show cutoff value.
4) Are there any correlations between TB/UGT1A1 and co-varieties such as age, sex, BMI, and
ALT? In addition, Is there correlation between TB and UGT1A1?
Minor
1) p9 in Discussion, “Previous studies reported the association of circulating TB levels with the
risk of NAFLD or NASH.” the citation for this description should be included.
2) The results of correlation between liver fat fraction with TB/UGT1A1 (with prevalence of
NAFLD, with grades of steatosis and in groups stratified by TB and so on) were distributed to
Table 2,3,4,6. It is recommended to organize and present the results in fewer numbers of tables.
Title: Relationship of circulating total bilirubin, UDP-glucuronosyltransferases 1A1 and the
development of non-alcoholic fatty liver disease: a cross-sectional study
Version: 2 Date: 07 Oct 2021
Reviewer's report:
Comments to the Author
In this study, the authors investigated the association between circulating TB /UGT1A1 and
liver fat fraction. Hepatic steatosis severity examined by MRI-PDFF was valuable and focusing
UGT1A1 besides total bilirubin was the novelty of this study. However, there is a lack of
assessment to understand the mechanism of the positive correlation of TB/UGT1A1 with fat
fraction. I have some comments and queries:
Major
1) The authors investigated circulating UGT1A1 and found correlation with fat fraction in the
NAFLD patients with severe steatosis. While the function of UGT1A1 in liver tissue especially
regarding gene variants has been well discussed so far, the meaning of calculating UGT1A1 in
blood is not elucidated. Are there any previous studies which looked at the circulating UGT1A1?
The authors should discuss the mechanism underlying elevated amount of UGT1A1 in blood.
2) Although a fair amount of previous study showed that serum bilirubin levels are inversely
associated with development of NAFLD/NASH as the authors described, this study found TB
was higher in the patients with moderate and severe steatosis. I suggest the author discuss why
the present study showed the different result from the previous reports which showed inversely
association between TB and NAFLD. In addition, investigating direct bilirubin and indirect
bilirubin would be valuable especially discussing the relation with UGT1A1 in this study.
3) The author presented cutoff value of TB and UGT1A1 on NAFLD. However, AUROC was
very low and predictive power is too weak to show cutoff value.
4) Are there any correlations between TB/UGT1A1 and co-varieties such as age, sex, BMI, and
ALT? In addition, Is there correlation between TB and UGT1A1?
Minor
1) p9 in Discussion, “Previous studies reported the association of circulating TB levels with the
risk of NAFLD or NASH.” the citation for this description should be included.
2) The results of correlation between liver fat fraction with TB/UGT1A1 (with prevalence of
NAFLD, with grades of steatosis and in groups stratified by TB and so on) were distributed to
Table 2,3,4,6. It is recommended to organize and present the results in fewer numbers of tables.
Please review this paper.
user
Title: Relationship of circulating total bilirubin, UDP-glucuronosyltransferases 1A1 and the
development of non-alcoholic fatty liver disease: a cross-sectional study
Version: 2 Date: 07 Oct 2021
Reviewer's report:
Comments to the Author
In this study, the authors investigated the association between circulating TB /UGT1A1 and
liver fat fraction. Hepatic steatosis severity examined by MRI-PDFF was valuable and focusing
UGT1A1 besides total bilirubin was the novelty of this study. However, there is a lack of
assessment to understand the mechanism of the positive correlation of TB/UGT1A1 with fat
fraction. I have some comments and queries:
Major
1) The authors investigated circulating UGT1A1 and found correlation with fat fraction in the
NAFLD patients with severe steatosis. While the function of UGT1A1 in liver tissue especially
regarding gene variants has been well discussed so far, the meaning of calculating UGT1A1 in
blood is not elucidated. Are there any previous studies which looked at the circulating UGT1A1?
The authors should discuss the mechanism underlying elevated amount of UGT1A1 in blood.
2) Although a fair amount of previous study showed that serum bilirubin levels are inversely
associated with development of NAFLD/NASH as the authors described, this study found TB
was higher in the patients with moderate and severe steatosis. I suggest the author discuss why
the present study showed the different result from the previous reports which showed inversely
association between TB and NAFLD. In addition, investigating direct bilirubin and indirect
bilirubin would be valuable especially discussing the relation with UGT1A1 in this study.
3) The author presented cutoff value of TB and UGT1A1 on NAFLD. However, AUROC was
very low and predictive power is too weak to show cutoff value.
4) Are there any correlations between TB/UGT1A1 and co-varieties such as age, sex, BMI, and
ALT? In addition, Is there correlation between TB and UGT1A1?
Minor
1) p9 in Discussion, “Previous studies reported the association of circulating TB levels with the
risk of NAFLD or NASH.” the citation for this description should be included.
2) The results of correlation between liver fat fraction with TB/UGT1A1 (with prevalence of
NAFLD, with grades of steatosis and in groups stratified by TB and so on) were distributed to
Table 2,3,4,6. It is recommended to organize and present the results in fewer numbers of tables.
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