Title: HBV pregenome RNA as a predictor of spontanous HBeAg seroconversion in HBeAg-
positive chronic hepatitis B patients
Version: 2 Date: 20 Aug 2023
Reviewer:  Ta-Wei Liu
Reviewer's report:
Dear Authors, congratulations on your important work, which we believe will further elucidate
the dynamic change of viral/immune activity and enhance prediction of e seroconversion among
CHB patients. Here are my comments:
Q0: In the referred study conducted by the same author (#Ref 17, Song et al. Journal of Medical
Virology, 2017), the serum sample of one patient among the 36 patients (Group B) was polluted,
so the patient was removed. The number of the patients in group B was 35. However, in the
current study, table 1 still showed 36 patients in Group B. What happened to the polluted serum
sample mentioned in 2017?
Q1: Table 2 showed the AUROC numbers of the HBV pgRNA level and the #HBV pgRNA at
week 12 and 28. Since the aim of the study was to find out the predicting power of HBV pgRNA
for spontaneous HBeAg seroconversion, please consider to mention the AUROC numbers in
Abstract, and show the AUROC figure legends in the manuscript.
Q2: In "Discussion" line 267 and 268 stated "HBV pgRNA is derived only from intrahepatic
cccDNA and not affected by NAs". Theoretically, if NA suppressed cccDNA replication,
pgRNA will eventually be suppressed. It had also been reported that "HBV pgRNA virion levels
increased after blocking the reverse transcription activity of HBV DNA polymerase" (Wang et
al. J Hepatol. 2016). What are the authors' opinions?
Q3.0: In "Discussion" line 315 and 316 stated "All the patients enrolled in this study are Chinese,
and the HBV genotype of the patients is B or C." It had been reported that spontaneous HBeAg
seroconversion occurred less frequently in patients with genotype C infection than those with
genotype B infection (Kao et al. Journal of Medical Virology. 2004.) Were the genotypes of the
54 enrolled patients available in the current study?
Q3.1: It had also been reported that spontaneous HBeAg seroconversion were not statistically
different between patients with low and high baseline serum HBV DNA levels(Kao et al. Journal
of Medical Virology. 2004.). However, immune active HBeAg(+) CHB patients with lower
pgRNA seemed to have better chance of HBeAg seroconversion since week 12 in the current
study. What are the aurthors' opinions?
Q4: There were some misspelling, such as "enlargred" in line 80 and "continously" in line 201.
Please recheck the spelling and format of this paper.
Title: HBV pregenome RNA as a predictor of spontanous HBeAg seroconversion in HBeAg-
positive chronic hepatitis B patients
Version: 2 Date: 20 Aug 2023
Reviewer:  Ta-Wei Liu
Reviewer's report:
Dear Authors, congratulations on your important work, which we believe will further elucidate
the dynamic change of viral/immune activity and enhance prediction of e seroconversion among
CHB patients. Here are my comments:
Q0: In the referred study conducted by the same author (#Ref 17, Song et al. Journal of Medical
Virology, 2017), the serum sample of one patient among the 36 patients (Group B) was polluted,
so the patient was removed. The number of the patients in group B was 35. However, in the
current study, table 1 still showed 36 patients in Group B. What happened to the polluted serum
sample mentioned in 2017?
Q1: Table 2 showed the AUROC numbers of the HBV pgRNA level and the #HBV pgRNA at
week 12 and 28. Since the aim of the study was to find out the predicting power of HBV pgRNA
for spontaneous HBeAg seroconversion, please consider to mention the AUROC numbers in
Abstract, and show the AUROC figure legends in the manuscript.
Q2: In "Discussion" line 267 and 268 stated "HBV pgRNA is derived only from intrahepatic
cccDNA and not affected by NAs". Theoretically, if NA suppressed cccDNA replication,
pgRNA will eventually be suppressed. It had also been reported that "HBV pgRNA virion levels
increased after blocking the reverse transcription activity of HBV DNA polymerase" (Wang et
al. J Hepatol. 2016). What are the authors' opinions?
Q3.0: In "Discussion" line 315 and 316 stated "All the patients enrolled in this study are Chinese,
and the HBV genotype of the patients is B or C." It had been reported that spontaneous HBeAg
seroconversion occurred less frequently in patients with genotype C infection than those with
genotype B infection (Kao et al. Journal of Medical Virology. 2004.) Were the genotypes of the
54 enrolled patients available in the current study?
Q3.1: It had also been reported that spontaneous HBeAg seroconversion were not statistically
different between patients with low and high baseline serum HBV DNA levels(Kao et al. Journal
of Medical Virology. 2004.). However, immune active HBeAg(+) CHB patients with lower
pgRNA seemed to have better chance of HBeAg seroconversion since week 12 in the current
study. What are the aurthors' opinions?
Q4: There were some misspelling, such as "enlargred" in line 80 and "continously" in line 201.
Please recheck the spelling and format of this paper.
Please review this paper.
user
Title: HBV pregenome RNA as a predictor of spontanous HBeAg seroconversion in HBeAg-
positive chronic hepatitis B patients
Version: 2 Date: 20 Aug 2023
Reviewer:  Ta-Wei Liu
Reviewer's report:
Dear Authors, congratulations on your important work, which we believe will further elucidate
the dynamic change of viral/immune activity and enhance prediction of e seroconversion among
CHB patients. Here are my comments:
Q0: In the referred study conducted by the same author (#Ref 17, Song et al. Journal of Medical
Virology, 2017), the serum sample of one patient among the 36 patients (Group B) was polluted,
so the patient was removed. The number of the patients in group B was 35. However, in the
current study, table 1 still showed 36 patients in Group B. What happened to the polluted serum
sample mentioned in 2017?
Q1: Table 2 showed the AUROC numbers of the HBV pgRNA level and the #HBV pgRNA at
week 12 and 28. Since the aim of the study was to find out the predicting power of HBV pgRNA
for spontaneous HBeAg seroconversion, please consider to mention the AUROC numbers in
Abstract, and show the AUROC figure legends in the manuscript.
Q2: In "Discussion" line 267 and 268 stated "HBV pgRNA is derived only from intrahepatic
cccDNA and not affected by NAs". Theoretically, if NA suppressed cccDNA replication,
pgRNA will eventually be suppressed. It had also been reported that "HBV pgRNA virion levels
increased after blocking the reverse transcription activity of HBV DNA polymerase" (Wang et
al. J Hepatol. 2016). What are the authors' opinions?
Q3.0: In "Discussion" line 315 and 316 stated "All the patients enrolled in this study are Chinese,
and the HBV genotype of the patients is B or C." It had been reported that spontaneous HBeAg
seroconversion occurred less frequently in patients with genotype C infection than those with
genotype B infection (Kao et al. Journal of Medical Virology. 2004.) Were the genotypes of the
54 enrolled patients available in the current study?
Q3.1: It had also been reported that spontaneous HBeAg seroconversion were not statistically
different between patients with low and high baseline serum HBV DNA levels(Kao et al. Journal
of Medical Virology. 2004.). However, immune active HBeAg(+) CHB patients with lower
pgRNA seemed to have better chance of HBeAg seroconversion since week 12 in the current
study. What are the aurthors' opinions?
Q4: There were some misspelling, such as "enlargred" in line 80 and "continously" in line 201.
Please recheck the spelling and format of this paper.
assistant