Title: Association of Chronic Hepatitis B Infection with Hepatic Steatosis and Injury in
Nonalcoholic Fatty Liver Disease Children
Version: 3 Date: 11 Oct 2023
Reviewer:  Toshifumi Yodoshi
Reviewer's report:
This study aims to investigate the effect of chronic hepatitis B infection (CBI) on hepatic
steatosis and assess the association between co-existing CBI and hepatic injury in the NAFLD
pediatric population with biopsy-proven data, which is a significant strength. While the data
is intriguing, there are substantial statistical issues, notably a time-lead bias. In fact, there are
significant differences in BMI and ALT between the two groups. These differences need to
be taken into account in the analysis. In this regard, using step-wise selection in multivariable
regression analysis is not appropriate. Age, gender, BMI (given the pediatric population, BMI
z-score should be used), ALT, platelet count, and either GGT or ALP should be adjusted for as
variables of clinical interest.
As it stands, I cannot evaluate this paper. However, if similar results can be demonstrated after
addressing these analyses, I believe there would be significant merit in conducting another peer-
review.
In addition, some minor modifications would be needed as follows.
1) Lines 78-79: Please cite the reference for the statement,
"Epidemiological evidence suggests an inverse association between CBI and hepatic steatosis."
2) Lines 108-111: Ensure that abbreviations are defined upon their first usage.
The diagnosis of NAFLD was based on the NAFLD Practice Guidance from the AASLD[1].
Chronic HBV infection (CBI) was determined by a positive serum hepatitis B surface antigen
(HBsAg) persisting for 6 months or longer, as defined by the American Association for the Study
of Liver Diseases (AASLD) 2018 Hepatitis B Guidance[14].
Title: Association of Chronic Hepatitis B Infection with Hepatic Steatosis and Injury in
Nonalcoholic Fatty Liver Disease Children
Version: 3 Date: 11 Oct 2023
Reviewer:  Toshifumi Yodoshi
Reviewer's report:
This study aims to investigate the effect of chronic hepatitis B infection (CBI) on hepatic
steatosis and assess the association between co-existing CBI and hepatic injury in the NAFLD
pediatric population with biopsy-proven data, which is a significant strength. While the data
is intriguing, there are substantial statistical issues, notably a time-lead bias. In fact, there are
significant differences in BMI and ALT between the two groups. These differences need to
be taken into account in the analysis. In this regard, using step-wise selection in multivariable
regression analysis is not appropriate. Age, gender, BMI (given the pediatric population, BMI
z-score should be used), ALT, platelet count, and either GGT or ALP should be adjusted for as
variables of clinical interest.
As it stands, I cannot evaluate this paper. However, if similar results can be demonstrated after
addressing these analyses, I believe there would be significant merit in conducting another peer-
review.
In addition, some minor modifications would be needed as follows.
1) Lines 78-79: Please cite the reference for the statement,
"Epidemiological evidence suggests an inverse association between CBI and hepatic steatosis."
2) Lines 108-111: Ensure that abbreviations are defined upon their first usage.
The diagnosis of NAFLD was based on the NAFLD Practice Guidance from the AASLD[1].
Chronic HBV infection (CBI) was determined by a positive serum hepatitis B surface antigen
(HBsAg) persisting for 6 months or longer, as defined by the American Association for the Study
of Liver Diseases (AASLD) 2018 Hepatitis B Guidance[14].
Please review this paper.
user
Title: Association of Chronic Hepatitis B Infection with Hepatic Steatosis and Injury in
Nonalcoholic Fatty Liver Disease Children
Version: 3 Date: 11 Oct 2023
Reviewer:  Toshifumi Yodoshi
Reviewer's report:
This study aims to investigate the effect of chronic hepatitis B infection (CBI) on hepatic
steatosis and assess the association between co-existing CBI and hepatic injury in the NAFLD
pediatric population with biopsy-proven data, which is a significant strength. While the data
is intriguing, there are substantial statistical issues, notably a time-lead bias. In fact, there are
significant differences in BMI and ALT between the two groups. These differences need to
be taken into account in the analysis. In this regard, using step-wise selection in multivariable
regression analysis is not appropriate. Age, gender, BMI (given the pediatric population, BMI
z-score should be used), ALT, platelet count, and either GGT or ALP should be adjusted for as
variables of clinical interest.
As it stands, I cannot evaluate this paper. However, if similar results can be demonstrated after
addressing these analyses, I believe there would be significant merit in conducting another peer-
review.
In addition, some minor modifications would be needed as follows.
1) Lines 78-79: Please cite the reference for the statement,
"Epidemiological evidence suggests an inverse association between CBI and hepatic steatosis."
2) Lines 108-111: Ensure that abbreviations are defined upon their first usage.
The diagnosis of NAFLD was based on the NAFLD Practice Guidance from the AASLD[1].
Chronic HBV infection (CBI) was determined by a positive serum hepatitis B surface antigen
(HBsAg) persisting for 6 months or longer, as defined by the American Association for the Study
of Liver Diseases (AASLD) 2018 Hepatitis B Guidance[14].
assistant