Title: Patients with chronic hepatitis B who have persistently normal alanine aminotransferase
or aged < 30 years may exhibit significant histologic damage
Version: 0 Date: 04 Jan 2024
Reviewer's report:
A. General Comments:
1. English language of the text needs considerable polishing. Correct some typing errors.
2. It is advisable that authors compare their histological findings to those of patients with an
ALT cutoff at 30 U/L for males and 19 U/L for females (Hepatology 2010; 51:1577, Hepatology
2012; 55:447) and also to the group of patients with ALT #40 IU/L and HBV DNA <2000 IU/
mL. Report any respective group differences of the corresponding stage and grade.
B. Major Comments:
1. (Line 2): Consider “may exhibit”.
2.  (Line 25): Authors should clarify whether “normal ALT” values were those at presentation
(baseline) only, or “persistently normal” ALT levels, observed over a defined time period.
3. (Line 25): The histological scoring system must appear at this point.
4. (Line 49-51): Please consider a change in this sentence. HBV DNA non detectability is the
expected outcome of nucleos(t)ide analog treatment for all patients. What is infrequent is the
elimination or seroconversion of HBsAg.
5. (Line 58): Authors must be aware that the term “inactive HBV carriers” (Hepatology
2018;67;1560) or “HBeAg-negative chronic HBV infection” (J Hepatol 2017;67:370), or “low
replicative chronic HBV infection” (Hepatol Int 2016;10:1), includes HBeAg-negative patients
with persistently normal serum ALT, HBV DNA #2000 IU/mL (and HBsAg #1000 IU/mL) and
not only HBeAg-negative patients with normal serum ALT.
6. (Line 89): Please mention whether the HBV DNA examination was made by qualitative or
quantitative PCR.
7. (Line 89): What percentage of HBsAg-positive patients, conforming with criteria 1 & 2,
underwent a liver biopsy? What was the total number of patients with HBV infection and co-
infection seen between 1999 and 2003 in the authors’ Center?
8. (Line 109): Please report of any major side effects of the liver biopsy procedure.
9. (Table 1, Line 3): In the footnote, the authors must indicate the upper limit of normal of AST,
ALT and GGT.
10. (Table 1, Male sex): Please discuss whether the great preponderance of males in your cohort
was due to limited hospital access of females or to other reasons.
11. (Table 1, Footnote): The number (and percentage) of HBeAg-positive and -negative patients
should appear in the Table.
12. (Table 2):  Tables 1 & 2 can be combined.
C. Minor Comment:
(Line 460): “Two subgroups”. Please correct and elsewhere.
Title: Patients with chronic hepatitis B who have persistently normal alanine aminotransferase
or aged < 30 years may exhibit significant histologic damage
Version: 0 Date: 04 Jan 2024
Reviewer's report:
A. General Comments:
1. English language of the text needs considerable polishing. Correct some typing errors.
2. It is advisable that authors compare their histological findings to those of patients with an
ALT cutoff at 30 U/L for males and 19 U/L for females (Hepatology 2010; 51:1577, Hepatology
2012; 55:447) and also to the group of patients with ALT #40 IU/L and HBV DNA <2000 IU/
mL. Report any respective group differences of the corresponding stage and grade.
B. Major Comments:
1. (Line 2): Consider “may exhibit”.
2.  (Line 25): Authors should clarify whether “normal ALT” values were those at presentation
(baseline) only, or “persistently normal” ALT levels, observed over a defined time period.
3. (Line 25): The histological scoring system must appear at this point.
4. (Line 49-51): Please consider a change in this sentence. HBV DNA non detectability is the
expected outcome of nucleos(t)ide analog treatment for all patients. What is infrequent is the
elimination or seroconversion of HBsAg.
5. (Line 58): Authors must be aware that the term “inactive HBV carriers” (Hepatology
2018;67;1560) or “HBeAg-negative chronic HBV infection” (J Hepatol 2017;67:370), or “low
replicative chronic HBV infection” (Hepatol Int 2016;10:1), includes HBeAg-negative patients
with persistently normal serum ALT, HBV DNA #2000 IU/mL (and HBsAg #1000 IU/mL) and
not only HBeAg-negative patients with normal serum ALT.
6. (Line 89): Please mention whether the HBV DNA examination was made by qualitative or
quantitative PCR.
7. (Line 89): What percentage of HBsAg-positive patients, conforming with criteria 1 & 2,
underwent a liver biopsy? What was the total number of patients with HBV infection and co-
infection seen between 1999 and 2003 in the authors’ Center?
8. (Line 109): Please report of any major side effects of the liver biopsy procedure.
9. (Table 1, Line 3): In the footnote, the authors must indicate the upper limit of normal of AST,
ALT and GGT.
10. (Table 1, Male sex): Please discuss whether the great preponderance of males in your cohort
was due to limited hospital access of females or to other reasons.
11. (Table 1, Footnote): The number (and percentage) of HBeAg-positive and -negative patients
should appear in the Table.
12. (Table 2):  Tables 1 & 2 can be combined.
C. Minor Comment:
(Line 460): “Two subgroups”. Please correct and elsewhere.
Please review this paper.
user
Title: Patients with chronic hepatitis B who have persistently normal alanine aminotransferase
or aged < 30 years may exhibit significant histologic damage
Version: 0 Date: 04 Jan 2024
Reviewer's report:
A. General Comments:
1. English language of the text needs considerable polishing. Correct some typing errors.
2. It is advisable that authors compare their histological findings to those of patients with an
ALT cutoff at 30 U/L for males and 19 U/L for females (Hepatology 2010; 51:1577, Hepatology
2012; 55:447) and also to the group of patients with ALT #40 IU/L and HBV DNA <2000 IU/
mL. Report any respective group differences of the corresponding stage and grade.
B. Major Comments:
1. (Line 2): Consider “may exhibit”.
2.  (Line 25): Authors should clarify whether “normal ALT” values were those at presentation
(baseline) only, or “persistently normal” ALT levels, observed over a defined time period.
3. (Line 25): The histological scoring system must appear at this point.
4. (Line 49-51): Please consider a change in this sentence. HBV DNA non detectability is the
expected outcome of nucleos(t)ide analog treatment for all patients. What is infrequent is the
elimination or seroconversion of HBsAg.
5. (Line 58): Authors must be aware that the term “inactive HBV carriers” (Hepatology
2018;67;1560) or “HBeAg-negative chronic HBV infection” (J Hepatol 2017;67:370), or “low
replicative chronic HBV infection” (Hepatol Int 2016;10:1), includes HBeAg-negative patients
with persistently normal serum ALT, HBV DNA #2000 IU/mL (and HBsAg #1000 IU/mL) and
not only HBeAg-negative patients with normal serum ALT.
6. (Line 89): Please mention whether the HBV DNA examination was made by qualitative or
quantitative PCR.
7. (Line 89): What percentage of HBsAg-positive patients, conforming with criteria 1 & 2,
underwent a liver biopsy? What was the total number of patients with HBV infection and co-
infection seen between 1999 and 2003 in the authors’ Center?
8. (Line 109): Please report of any major side effects of the liver biopsy procedure.
9. (Table 1, Line 3): In the footnote, the authors must indicate the upper limit of normal of AST,
ALT and GGT.
10. (Table 1, Male sex): Please discuss whether the great preponderance of males in your cohort
was due to limited hospital access of females or to other reasons.
11. (Table 1, Footnote): The number (and percentage) of HBeAg-positive and -negative patients
should appear in the Table.
12. (Table 2):  Tables 1 & 2 can be combined.
C. Minor Comment:
(Line 460): “Two subgroups”. Please correct and elsewhere.
assistant