Title: HBV pregenome RNA as a predictor of spontanous HBeAg seroconversion in HBeAg-
positive chronic hepatitis B patients
Version: 2 Date: 17 Aug 2023
Reviewer's report:
Serum HBV pgRNA levels were found to be correlated with serum HBV DNA levels as well
as quantitative HBsAg in CHB patient. In this study, Song et al. investigated the association
between dynamic HBV pgRNA and spontaneous HBeAg seroconversion in untreated HBeAg-
positive patients in immune active phase. They found that HBV pgRNA and the reduction from
baseline (#HBV pgRNA) at week 12 or 28 were powerful predictors for spontaneous HBeAg
seroconversion. Although the findings are clinically important, several issues are worthy of
attention.
Specific comments
1. Is this study prospective or retrospective? The number of patients is too small to have
convincing results.
2. The patients of control group were selected by simple random sampling. Why not use
propensity score matching?
3. Are the patients in this study the same as the paper published in Journal of Medical Virology
in 2014 and 2017 (Ref No. 15 and 17)? If so, is there any updated follow-up data.
4. The authors suggest using HBV pgRNA and the reduction from baseline (#HBV pgRNA)
at week 28 to predict spontaneous HBeAg seroconversion. This suggestion indicates that the
patient should be observed for 28 weeks during an acute flare up before deciding to start antiviral
therapy. The 28-week follow-up period seems too long. The authors should compare the PPV
and NPV of HBV DNA at week 12 and week 28.
5. The method to evaluate the predictive values of the HBV pgRNA should be mentioned in the
section of Statistical Analyses. In addition, the figure of the AUROCs of the HBV pgRNA level
and the #HBV pgRNA at week 12 and 28 should be provided
6. How many patients in this study were cirrhotic patients? Is the dynamics of HBV RNA related
to liver cirrhosis?
Title: HBV pregenome RNA as a predictor of spontanous HBeAg seroconversion in HBeAg-
positive chronic hepatitis B patients
Version: 2 Date: 17 Aug 2023
Reviewer's report:
Serum HBV pgRNA levels were found to be correlated with serum HBV DNA levels as well
as quantitative HBsAg in CHB patient. In this study, Song et al. investigated the association
between dynamic HBV pgRNA and spontaneous HBeAg seroconversion in untreated HBeAg-
positive patients in immune active phase. They found that HBV pgRNA and the reduction from
baseline (#HBV pgRNA) at week 12 or 28 were powerful predictors for spontaneous HBeAg
seroconversion. Although the findings are clinically important, several issues are worthy of
attention.
Specific comments
1. Is this study prospective or retrospective? The number of patients is too small to have
convincing results.
2. The patients of control group were selected by simple random sampling. Why not use
propensity score matching?
3. Are the patients in this study the same as the paper published in Journal of Medical Virology
in 2014 and 2017 (Ref No. 15 and 17)? If so, is there any updated follow-up data.
4. The authors suggest using HBV pgRNA and the reduction from baseline (#HBV pgRNA)
at week 28 to predict spontaneous HBeAg seroconversion. This suggestion indicates that the
patient should be observed for 28 weeks during an acute flare up before deciding to start antiviral
therapy. The 28-week follow-up period seems too long. The authors should compare the PPV
and NPV of HBV DNA at week 12 and week 28.
5. The method to evaluate the predictive values of the HBV pgRNA should be mentioned in the
section of Statistical Analyses. In addition, the figure of the AUROCs of the HBV pgRNA level
and the #HBV pgRNA at week 12 and 28 should be provided
6. How many patients in this study were cirrhotic patients? Is the dynamics of HBV RNA related
to liver cirrhosis?
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: 17 Aug 2023
Reviewer's report:
Serum HBV pgRNA levels were found to be correlated with serum HBV DNA levels as well
as quantitative HBsAg in CHB patient. In this study, Song et al. investigated the association
between dynamic HBV pgRNA and spontaneous HBeAg seroconversion in untreated HBeAg-
positive patients in immune active phase. They found that HBV pgRNA and the reduction from
baseline (#HBV pgRNA) at week 12 or 28 were powerful predictors for spontaneous HBeAg
seroconversion. Although the findings are clinically important, several issues are worthy of
attention.
Specific comments
1. Is this study prospective or retrospective? The number of patients is too small to have
convincing results.
2. The patients of control group were selected by simple random sampling. Why not use
propensity score matching?
3. Are the patients in this study the same as the paper published in Journal of Medical Virology
in 2014 and 2017 (Ref No. 15 and 17)? If so, is there any updated follow-up data.
4. The authors suggest using HBV pgRNA and the reduction from baseline (#HBV pgRNA)
at week 28 to predict spontaneous HBeAg seroconversion. This suggestion indicates that the
patient should be observed for 28 weeks during an acute flare up before deciding to start antiviral
therapy. The 28-week follow-up period seems too long. The authors should compare the PPV
and NPV of HBV DNA at week 12 and week 28.
5. The method to evaluate the predictive values of the HBV pgRNA should be mentioned in the
section of Statistical Analyses. In addition, the figure of the AUROCs of the HBV pgRNA level
and the #HBV pgRNA at week 12 and 28 should be provided
6. How many patients in this study were cirrhotic patients? Is the dynamics of HBV RNA related
to liver cirrhosis?
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