Title: Noninvasive models for the prediction of liver fibrosis in patients with chronic hepatitis B
Version: 1 Date: 10 Apr 2024
Reviewer's report:
Dear all,
Thank you for accepting the comments.
I believe that the manuscript can be further improved. Please read the following comments:
Abbreviations: AST, aspartate aminotransferase; ALT, alanine aminotransferase; PLT, . platelet;
APRI, aspartate aminotransferase to platelet ratio index; FIB-4, fibrosis-4 score; GGT, gamma-
glutamyl transpeptidase; PLT, platelet; -You have PLT two times.
Methods
A total of 1210 CHB patients who underwent liver biopsy and routine laboratory tests were
retrospectively included. Logistic regression models were used for the prediction, and the area
under the receiver operating characteristic (AUROC) was used to assess the diagnostic accuracy.
Please state in clear manner that the patients were divided into two groups: patients with no
significant fibrosis (control group) and patients with significant fibrosis
2.2 Laboratory testing
The height and weight of the study participants were measured using the SK-X80 electronic
measuring instrument from Shuangjia Electronics. The patients were instructed to fast for 8 h.
The following morning, a suitable amount of venous blood was drawn…. What is suitable?
Please be precise e.g. 10 ml of blood or whatever amount of blood you have taken.
.. These indicators are calculated and have to be determined from the literature[9,10]. I think that
it would be better if you replace this sentence with -Non invasive biomarkers were calculated :
GPR, FIB-4 and APRI are calculated as follows: GPR = (GGT/upper limit of normal [ULN])/
PLT (109 /L) × 100, FIB-4 = [age (years) × AST (U/L)]/[PLT (109/L) × ALT1/2 (U/L)], APRI
= (AST/ULN)/PLT (109/L) × 100.
For routine blood tests, a fully automated hematology analyzer (Myriad 6800PLUS) was used.
For liver function, including fasting blood glucose (FBG), lipids, uric acid (UA), and other
indicators, a fully automated biochemical analyzer (Beckman AU5800) was employed. For
routine coagulation test, a fully automated coagulation analyzer (Wolfen Hemo CELL750) was
utilized… Pease correct it to For liver function tests (liver enzymes, bilirubin levels, proteins
levels) and for prothrombin time a fully automated biochemical analyzer (Beckman AU5800
and a fully automated coagulation analyzer (Wolfen Hemo CELL750) were utilized.
For HBV DNA tests,realtime fluorescence quantitative PCR (Roche Cobas CAP/CTM 96) was
utilized. Please state what is the lower limit of detection? For example, 10 IU/ml? You have to
give the specifics for HBV DNA testing..
3.1 Comparison of general data
A total of 1210 cases enrolled, with 935(77.3%) cases in the non-significant hepatic fibrosis
group and 275(22.7%) cases in the significant hepatic fibrosis group. Please Clarify that this is
your control group -non-significant hepatic fibrosis group (control group)
3.3 Different predictive values of AST/ALT, APRI, FIB-4, GPR in HBeAg-positive and
HBeAg-negative patients
Table 3 presents the results stratified by HbeAg status- Please correct it to HBeAg
. Stratified by HbeAg status, the cut-off values, sensitivity, and specificity of four predictors in
predicting stage S2–S4 and S3–S4 liver fibrosis are presented in Table 3. Figure 2 presents the
ROC curves stratified by HbeAg status. Please correct it to HBeAg
,, Therefore, compared to invasive and imaging-based tests, non-invasive fibrosis assessment
based on serologic tests has been common used by Chinese scholars. – Commonly
…In this study, patients with CHB were divided into control group and advanced fibrosis group
based on the results of liver biopsy… In this study, patients with CHB were divided into two
groups based on the results of liver biopsy: patients with non-significant fibrosis (control group)
and patients with advanced fibrosis. The results showed that….
…. and the area under the ROC curve (AUC) of APRI- Please correct AUC for APRI instead
of AUC for APRI was 0.63 for significant fibrosis and 0.68 for advanced fibrosis, which were
higher than FIB-4 and AST/ALT.  Please state the AUCs for FIB-4 and AST/ALT here since
you are comparing them but you are not providing values
…This is because APRI contains AST and PLT indicators, which can exclude the effect of
abnormally elevated transaminases due to the active phase of hepatitis therefore APRI is of
higher clinical value in evaluating the degree of liver fibrosis….. I do not understand this? APRI
contains AST, and it is a transaminase. Please rephrase it.
…. Besides, the performances of APRI and FIB-4 for the diagnosis of liver fibrosis is similar to
our study24-26. … You do not need the word Besides
Table 1. Please include the numbers for HBeAg negative patients as well.
Table 1. Please rephrase Positive HBeAg to HBeAg positive
Table 2. Please include the predictive values of your indicators for patients with no significant
fibrosis
Title: Noninvasive models for the prediction of liver fibrosis in patients with chronic hepatitis B
Version: 1 Date: 10 Apr 2024
Reviewer's report:
Dear all,
Thank you for accepting the comments.
I believe that the manuscript can be further improved. Please read the following comments:
Abbreviations: AST, aspartate aminotransferase; ALT, alanine aminotransferase; PLT, . platelet;
APRI, aspartate aminotransferase to platelet ratio index; FIB-4, fibrosis-4 score; GGT, gamma-
glutamyl transpeptidase; PLT, platelet; -You have PLT two times.
Methods
A total of 1210 CHB patients who underwent liver biopsy and routine laboratory tests were
retrospectively included. Logistic regression models were used for the prediction, and the area
under the receiver operating characteristic (AUROC) was used to assess the diagnostic accuracy.
Please state in clear manner that the patients were divided into two groups: patients with no
significant fibrosis (control group) and patients with significant fibrosis
2.2 Laboratory testing
The height and weight of the study participants were measured using the SK-X80 electronic
measuring instrument from Shuangjia Electronics. The patients were instructed to fast for 8 h.
The following morning, a suitable amount of venous blood was drawn…. What is suitable?
Please be precise e.g. 10 ml of blood or whatever amount of blood you have taken.
.. These indicators are calculated and have to be determined from the literature[9,10]. I think that
it would be better if you replace this sentence with -Non invasive biomarkers were calculated :
GPR, FIB-4 and APRI are calculated as follows: GPR = (GGT/upper limit of normal [ULN])/
PLT (109 /L) × 100, FIB-4 = [age (years) × AST (U/L)]/[PLT (109/L) × ALT1/2 (U/L)], APRI
= (AST/ULN)/PLT (109/L) × 100.
For routine blood tests, a fully automated hematology analyzer (Myriad 6800PLUS) was used.
For liver function, including fasting blood glucose (FBG), lipids, uric acid (UA), and other
indicators, a fully automated biochemical analyzer (Beckman AU5800) was employed. For
routine coagulation test, a fully automated coagulation analyzer (Wolfen Hemo CELL750) was
utilized… Pease correct it to For liver function tests (liver enzymes, bilirubin levels, proteins
levels) and for prothrombin time a fully automated biochemical analyzer (Beckman AU5800
and a fully automated coagulation analyzer (Wolfen Hemo CELL750) were utilized.
For HBV DNA tests,realtime fluorescence quantitative PCR (Roche Cobas CAP/CTM 96) was
utilized. Please state what is the lower limit of detection? For example, 10 IU/ml? You have to
give the specifics for HBV DNA testing..
3.1 Comparison of general data
A total of 1210 cases enrolled, with 935(77.3%) cases in the non-significant hepatic fibrosis
group and 275(22.7%) cases in the significant hepatic fibrosis group. Please Clarify that this is
your control group -non-significant hepatic fibrosis group (control group)
3.3 Different predictive values of AST/ALT, APRI, FIB-4, GPR in HBeAg-positive and
HBeAg-negative patients
Table 3 presents the results stratified by HbeAg status- Please correct it to HBeAg
. Stratified by HbeAg status, the cut-off values, sensitivity, and specificity of four predictors in
predicting stage S2–S4 and S3–S4 liver fibrosis are presented in Table 3. Figure 2 presents the
ROC curves stratified by HbeAg status. Please correct it to HBeAg
,, Therefore, compared to invasive and imaging-based tests, non-invasive fibrosis assessment
based on serologic tests has been common used by Chinese scholars. – Commonly
…In this study, patients with CHB were divided into control group and advanced fibrosis group
based on the results of liver biopsy… In this study, patients with CHB were divided into two
groups based on the results of liver biopsy: patients with non-significant fibrosis (control group)
and patients with advanced fibrosis. The results showed that….
…. and the area under the ROC curve (AUC) of APRI- Please correct AUC for APRI instead
of AUC for APRI was 0.63 for significant fibrosis and 0.68 for advanced fibrosis, which were
higher than FIB-4 and AST/ALT.  Please state the AUCs for FIB-4 and AST/ALT here since
you are comparing them but you are not providing values
…This is because APRI contains AST and PLT indicators, which can exclude the effect of
abnormally elevated transaminases due to the active phase of hepatitis therefore APRI is of
higher clinical value in evaluating the degree of liver fibrosis….. I do not understand this? APRI
contains AST, and it is a transaminase. Please rephrase it.
…. Besides, the performances of APRI and FIB-4 for the diagnosis of liver fibrosis is similar to
our study24-26. … You do not need the word Besides
Table 1. Please include the numbers for HBeAg negative patients as well.
Table 1. Please rephrase Positive HBeAg to HBeAg positive
Table 2. Please include the predictive values of your indicators for patients with no significant
fibrosis
Please review this paper.
user
Title: Noninvasive models for the prediction of liver fibrosis in patients with chronic hepatitis B
Version: 1 Date: 10 Apr 2024
Reviewer's report:
Dear all,
Thank you for accepting the comments.
I believe that the manuscript can be further improved. Please read the following comments:
Abbreviations: AST, aspartate aminotransferase; ALT, alanine aminotransferase; PLT, . platelet;
APRI, aspartate aminotransferase to platelet ratio index; FIB-4, fibrosis-4 score; GGT, gamma-
glutamyl transpeptidase; PLT, platelet; -You have PLT two times.
Methods
A total of 1210 CHB patients who underwent liver biopsy and routine laboratory tests were
retrospectively included. Logistic regression models were used for the prediction, and the area
under the receiver operating characteristic (AUROC) was used to assess the diagnostic accuracy.
Please state in clear manner that the patients were divided into two groups: patients with no
significant fibrosis (control group) and patients with significant fibrosis
2.2 Laboratory testing
The height and weight of the study participants were measured using the SK-X80 electronic
measuring instrument from Shuangjia Electronics. The patients were instructed to fast for 8 h.
The following morning, a suitable amount of venous blood was drawn…. What is suitable?
Please be precise e.g. 10 ml of blood or whatever amount of blood you have taken.
.. These indicators are calculated and have to be determined from the literature[9,10]. I think that
it would be better if you replace this sentence with -Non invasive biomarkers were calculated :
GPR, FIB-4 and APRI are calculated as follows: GPR = (GGT/upper limit of normal [ULN])/
PLT (109 /L) × 100, FIB-4 = [age (years) × AST (U/L)]/[PLT (109/L) × ALT1/2 (U/L)], APRI
= (AST/ULN)/PLT (109/L) × 100.
For routine blood tests, a fully automated hematology analyzer (Myriad 6800PLUS) was used.
For liver function, including fasting blood glucose (FBG), lipids, uric acid (UA), and other
indicators, a fully automated biochemical analyzer (Beckman AU5800) was employed. For
routine coagulation test, a fully automated coagulation analyzer (Wolfen Hemo CELL750) was
utilized… Pease correct it to For liver function tests (liver enzymes, bilirubin levels, proteins
levels) and for prothrombin time a fully automated biochemical analyzer (Beckman AU5800
and a fully automated coagulation analyzer (Wolfen Hemo CELL750) were utilized.
For HBV DNA tests,realtime fluorescence quantitative PCR (Roche Cobas CAP/CTM 96) was
utilized. Please state what is the lower limit of detection? For example, 10 IU/ml? You have to
give the specifics for HBV DNA testing..
3.1 Comparison of general data
A total of 1210 cases enrolled, with 935(77.3%) cases in the non-significant hepatic fibrosis
group and 275(22.7%) cases in the significant hepatic fibrosis group. Please Clarify that this is
your control group -non-significant hepatic fibrosis group (control group)
3.3 Different predictive values of AST/ALT, APRI, FIB-4, GPR in HBeAg-positive and
HBeAg-negative patients
Table 3 presents the results stratified by HbeAg status- Please correct it to HBeAg
. Stratified by HbeAg status, the cut-off values, sensitivity, and specificity of four predictors in
predicting stage S2–S4 and S3–S4 liver fibrosis are presented in Table 3. Figure 2 presents the
ROC curves stratified by HbeAg status. Please correct it to HBeAg
,, Therefore, compared to invasive and imaging-based tests, non-invasive fibrosis assessment
based on serologic tests has been common used by Chinese scholars. – Commonly
…In this study, patients with CHB were divided into control group and advanced fibrosis group
based on the results of liver biopsy… In this study, patients with CHB were divided into two
groups based on the results of liver biopsy: patients with non-significant fibrosis (control group)
and patients with advanced fibrosis. The results showed that….
…. and the area under the ROC curve (AUC) of APRI- Please correct AUC for APRI instead
of AUC for APRI was 0.63 for significant fibrosis and 0.68 for advanced fibrosis, which were
higher than FIB-4 and AST/ALT.  Please state the AUCs for FIB-4 and AST/ALT here since
you are comparing them but you are not providing values
…This is because APRI contains AST and PLT indicators, which can exclude the effect of
abnormally elevated transaminases due to the active phase of hepatitis therefore APRI is of
higher clinical value in evaluating the degree of liver fibrosis….. I do not understand this? APRI
contains AST, and it is a transaminase. Please rephrase it.
…. Besides, the performances of APRI and FIB-4 for the diagnosis of liver fibrosis is similar to
our study24-26. … You do not need the word Besides
Table 1. Please include the numbers for HBeAg negative patients as well.
Table 1. Please rephrase Positive HBeAg to HBeAg positive
Table 2. Please include the predictive values of your indicators for patients with no significant
fibrosis
assistant