Title: Development and validation of a new predictive model for the immune tolerance stage of
chronic HBV infection based on the liver histopathological changes
Version: 3 Date: 31 Mar 2025
Reviewer's report:
Dear Authors,
Congratulations on your innovative contribution in utilizing HBeAg levels to identify active
hepatitis in immune-tolerant stage CHB patients. Below are my comments:
Q0. Automated Chemiluminescence Immunoanalyzer: Please specify the brand and model of
the automated chemiluminescence immunoanalyzer used for the semiquantitative detection of
serum HBeAg levels.
Q1. HBcrAg vs. HBeAg in Distinguishing Active/Inactive Status: HBV core-related antigen
(HBcrAg), which includes HBcIg, HBeAg, and the 22-kDa precore protein, has been reported
to differentiate active hepatitis (>4.0 log) from inactive status (<3.0 log). What are the authors’
perspectives on the comparative performance of HBcrAg versus HBeAg in distinguishing the
active/inactive status of immune-tolerant CHB patients?
Q2.0 Exclusion Criteria - Antiviral Therapy: Regarding exclusion criterion #2—"patients treated
with interferon-# or nucleos(t)ide analogs in the last 6 months"—what is the rationale for this
specific time frame? Why not exclude all patients with prior antiviral therapy experience?
Q2.1 Exclusion Criteria - Fatty Liver: In exclusion criterion #3—"patients with moderate to
severe fatty liver, alcoholic liver disease, drug-induced liver injury, autoimmune liver disease,
or hereditary liver disease"—how did the authors define moderate and severe fatty liver?
Q3. HBcAb Levels in Tables: Why are HBcAb levels included in the tables? What is the clinical
significance of elevated HBcAb levels in CHB patients?
Q4. HBeAg Levels in Table 1: How were HBeAg levels calculated in Table 1? Were HBeAg
levels from HBeAg-negative patients included in these calculations?
Q5. Table 2 Title Correction: The title of Table 2, "Comparative analysis of IT stage and IC
stage of patients with CHB," should be revised to: "Comparative analysis of IT and IC stages
in HBeAg-positive CHB patients."
Q6. English Language Editing: Has the manuscript undergone professional English editing?
Some grammatical issues (e.g., in the Discussion: "However, liver pathological changes in their
study did not be included.") and spelling errors (e.g., in "ROC curve analysis in the IT and IC
stages of CHB patients," the phrase "The cutoff value under the maximum Jordan?? index is
161 × 10/L.") require correction.
Title: Development and validation of a new predictive model for the immune tolerance stage of
chronic HBV infection based on the liver histopathological changes
Version: 3 Date: 31 Mar 2025
Reviewer's report:
Dear Authors,
Congratulations on your innovative contribution in utilizing HBeAg levels to identify active
hepatitis in immune-tolerant stage CHB patients. Below are my comments:
Q0. Automated Chemiluminescence Immunoanalyzer: Please specify the brand and model of
the automated chemiluminescence immunoanalyzer used for the semiquantitative detection of
serum HBeAg levels.
Q1. HBcrAg vs. HBeAg in Distinguishing Active/Inactive Status: HBV core-related antigen
(HBcrAg), which includes HBcIg, HBeAg, and the 22-kDa precore protein, has been reported
to differentiate active hepatitis (>4.0 log) from inactive status (<3.0 log). What are the authors’
perspectives on the comparative performance of HBcrAg versus HBeAg in distinguishing the
active/inactive status of immune-tolerant CHB patients?
Q2.0 Exclusion Criteria - Antiviral Therapy: Regarding exclusion criterion #2—"patients treated
with interferon-# or nucleos(t)ide analogs in the last 6 months"—what is the rationale for this
specific time frame? Why not exclude all patients with prior antiviral therapy experience?
Q2.1 Exclusion Criteria - Fatty Liver: In exclusion criterion #3—"patients with moderate to
severe fatty liver, alcoholic liver disease, drug-induced liver injury, autoimmune liver disease,
or hereditary liver disease"—how did the authors define moderate and severe fatty liver?
Q3. HBcAb Levels in Tables: Why are HBcAb levels included in the tables? What is the clinical
significance of elevated HBcAb levels in CHB patients?
Q4. HBeAg Levels in Table 1: How were HBeAg levels calculated in Table 1? Were HBeAg
levels from HBeAg-negative patients included in these calculations?
Q5. Table 2 Title Correction: The title of Table 2, "Comparative analysis of IT stage and IC
stage of patients with CHB," should be revised to: "Comparative analysis of IT and IC stages
in HBeAg-positive CHB patients."
Q6. English Language Editing: Has the manuscript undergone professional English editing?
Some grammatical issues (e.g., in the Discussion: "However, liver pathological changes in their
study did not be included.") and spelling errors (e.g., in "ROC curve analysis in the IT and IC
stages of CHB patients," the phrase "The cutoff value under the maximum Jordan?? index is
161 × 10/L.") require correction.
Please review this paper.
user
Title: Development and validation of a new predictive model for the immune tolerance stage of
chronic HBV infection based on the liver histopathological changes
Version: 3 Date: 31 Mar 2025
Reviewer's report:
Dear Authors,
Congratulations on your innovative contribution in utilizing HBeAg levels to identify active
hepatitis in immune-tolerant stage CHB patients. Below are my comments:
Q0. Automated Chemiluminescence Immunoanalyzer: Please specify the brand and model of
the automated chemiluminescence immunoanalyzer used for the semiquantitative detection of
serum HBeAg levels.
Q1. HBcrAg vs. HBeAg in Distinguishing Active/Inactive Status: HBV core-related antigen
(HBcrAg), which includes HBcIg, HBeAg, and the 22-kDa precore protein, has been reported
to differentiate active hepatitis (>4.0 log) from inactive status (<3.0 log). What are the authors’
perspectives on the comparative performance of HBcrAg versus HBeAg in distinguishing the
active/inactive status of immune-tolerant CHB patients?
Q2.0 Exclusion Criteria - Antiviral Therapy: Regarding exclusion criterion #2—"patients treated
with interferon-# or nucleos(t)ide analogs in the last 6 months"—what is the rationale for this
specific time frame? Why not exclude all patients with prior antiviral therapy experience?
Q2.1 Exclusion Criteria - Fatty Liver: In exclusion criterion #3—"patients with moderate to
severe fatty liver, alcoholic liver disease, drug-induced liver injury, autoimmune liver disease,
or hereditary liver disease"—how did the authors define moderate and severe fatty liver?
Q3. HBcAb Levels in Tables: Why are HBcAb levels included in the tables? What is the clinical
significance of elevated HBcAb levels in CHB patients?
Q4. HBeAg Levels in Table 1: How were HBeAg levels calculated in Table 1? Were HBeAg
levels from HBeAg-negative patients included in these calculations?
Q5. Table 2 Title Correction: The title of Table 2, "Comparative analysis of IT stage and IC
stage of patients with CHB," should be revised to: "Comparative analysis of IT and IC stages
in HBeAg-positive CHB patients."
Q6. English Language Editing: Has the manuscript undergone professional English editing?
Some grammatical issues (e.g., in the Discussion: "However, liver pathological changes in their
study did not be included.") and spelling errors (e.g., in "ROC curve analysis in the IT and IC
stages of CHB patients," the phrase "The cutoff value under the maximum Jordan?? index is
161 × 10/L.") require correction.
assistant