Reviewer's report
Title:Efficacy of telbivudine in Taiwanese chronic hepatitis B patients compared
with GLOBE extension study and predicting treatment outcome by HBV DNA
kinetics at Week 24
Version: 1Date:6 July 2012
Reviewer: Jia-Horng Kao
Reviewer's report:
General Comments:
At present, there are two major categories of chronic hepatitis B (CHB) therapy:
standard or pegylated interferon alpha and nucleos(t)ide analogues (NAs),
including lamivudine (LAM), telbivudine (LdT), entecavir (ETV), adefovir dipivoxil
(ADV) and tenofovir disoproxil furamate (TDF). Although the new generation NAs
such as ETV and TDF are potent and effective with less drug resistance for the
treatment of CHB, the majority of CHB patients require long-term treatment to
maintain on-treatment viral suppression. Previous pivotal trials showed that
HBeAg-positive or –negative CHB patients treated with LdT had a significantly
greater reduction of serum HBV DNA level than those treated with LAM.
Nevertheless, like LAM, virological response to LdT decreases over time due to
the emergence of drug resistance to LdT. In this sub-study of GLOBE trial, Hsu
et al. investigated the results of 4-year LdT treatment in Taiwanese patients.
They found that the long-term efficacy of LdT in Taiwanese patients was
consistent with the GLOBE study. They also found a reduction of HBV DNA
levels > 5 log 10 copies/ml at week 24 could predict favorable outcomes in
patients with high baseline HBV DNA levels. Although their data are interesting
and potentially important, the major limitations include small patient number and
the lack of multivariate analysis to determine the predictors of treatment
outcomes. In addition, several issues are worthy of attention.
Specific Comments:
1. The major limitations are small patient number and the lack of multivariate
analysis to determine factors predictive of treatment outcomes. These flaws
make their conclusions less convincing.
2. In HBV DNA kinetics study, the baseline HBV DNA level of patients with HBV
DNA reduction # 5 log10 copies/ml at week 24 was lower than those with HBV
DNA reduction > 5 log10copies/ml at week 24. It is thus interesting to know which
is the predictor of favorable treatment outcome, baseline HBV DNA, or HBV DNA
reduction > 5 log10copies/ml at week 24, or undetectable HBV DNA at week 24?
To this end, multivariate analysis should be performed to answer this important
issue.
3. In this study, Taiwanese patients seemed to have a lower cumulative HBeAg
seroconversion rate as well as the proportion of patients achieved undetectable
HBV DNA at Year 4 and bear a higher genotypic resistance rate than those in the
extension 2303 study. The authors might have a good explanation for the
discrepant results.
4. In this study, HBsAg kinetics during treatment was only analyzed in 6
HBeAg-positive patients. Because of small patient number, it is premature to
conclude that most Taiwanese patients had a rapid decline in HBsAg levels
during LdT treatment.
5. High HBsAg loss or seroconversion rate was observed in patients with a rapid
decline in HBsAg level from baseline to week 24. The authors should provide the
overall HBsAg loss/seroconversion rate in all Taiwanese patients. In addition, the
incidence of HBsAg loss or seroconversion in these patients is much higher than
previously reported data. Therefore, the authors should provide the data of HBV
DNA levels at the time of HBsAg loss.
6. The association of HBV genotype with response or resistance to NAs remains
unclear. Thus, the impact of HBV genotype on the response or resistance to LdT
therapy in Taiwanese patients needs to be addressed.
7. In Table 1, the authors should provide the P value of comparison between
patients with HBV DNA reduction # or > 5 log10copies/ml at week 24 in the HBV
DNA kinetics study.
8. In Table 4, the title describes “….telbivudine treatment in HBeAg-positive
Taiwanese patients….”. However, this table also includes HBeAg-negative
patients.
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests'
Reviewer's report
Title:Efficacy of telbivudine in Taiwanese chronic hepatitis B patients compared
with GLOBE extension study and predicting treatment outcome by HBV DNA
kinetics at Week 24
Version: 1Date:6 July 2012
Reviewer: Jia-Horng Kao
Reviewer's report:
General Comments:
At present, there are two major categories of chronic hepatitis B (CHB) therapy:
standard or pegylated interferon alpha and nucleos(t)ide analogues (NAs),
including lamivudine (LAM), telbivudine (LdT), entecavir (ETV), adefovir dipivoxil
(ADV) and tenofovir disoproxil furamate (TDF). Although the new generation NAs
such as ETV and TDF are potent and effective with less drug resistance for the
treatment of CHB, the majority of CHB patients require long-term treatment to
maintain on-treatment viral suppression. Previous pivotal trials showed that
HBeAg-positive or –negative CHB patients treated with LdT had a significantly
greater reduction of serum HBV DNA level than those treated with LAM.
Nevertheless, like LAM, virological response to LdT decreases over time due to
the emergence of drug resistance to LdT. In this sub-study of GLOBE trial, Hsu
et al. investigated the results of 4-year LdT treatment in Taiwanese patients.
They found that the long-term efficacy of LdT in Taiwanese patients was
consistent with the GLOBE study. They also found a reduction of HBV DNA
levels > 5 log 10 copies/ml at week 24 could predict favorable outcomes in
patients with high baseline HBV DNA levels. Although their data are interesting
and potentially important, the major limitations include small patient number and
the lack of multivariate analysis to determine the predictors of treatment
outcomes. In addition, several issues are worthy of attention.
Specific Comments:
1. The major limitations are small patient number and the lack of multivariate
analysis to determine factors predictive of treatment outcomes. These flaws
make their conclusions less convincing.
2. In HBV DNA kinetics study, the baseline HBV DNA level of patients with HBV
DNA reduction # 5 log10 copies/ml at week 24 was lower than those with HBV
DNA reduction > 5 log10copies/ml at week 24. It is thus interesting to know which
is the predictor of favorable treatment outcome, baseline HBV DNA, or HBV DNA
reduction > 5 log10copies/ml at week 24, or undetectable HBV DNA at week 24?
To this end, multivariate analysis should be performed to answer this important
issue.
3. In this study, Taiwanese patients seemed to have a lower cumulative HBeAg
seroconversion rate as well as the proportion of patients achieved undetectable
HBV DNA at Year 4 and bear a higher genotypic resistance rate than those in the
extension 2303 study. The authors might have a good explanation for the
discrepant results.
4. In this study, HBsAg kinetics during treatment was only analyzed in 6
HBeAg-positive patients. Because of small patient number, it is premature to
conclude that most Taiwanese patients had a rapid decline in HBsAg levels
during LdT treatment.
5. High HBsAg loss or seroconversion rate was observed in patients with a rapid
decline in HBsAg level from baseline to week 24. The authors should provide the
overall HBsAg loss/seroconversion rate in all Taiwanese patients. In addition, the
incidence of HBsAg loss or seroconversion in these patients is much higher than
previously reported data. Therefore, the authors should provide the data of HBV
DNA levels at the time of HBsAg loss.
6. The association of HBV genotype with response or resistance to NAs remains
unclear. Thus, the impact of HBV genotype on the response or resistance to LdT
therapy in Taiwanese patients needs to be addressed.
7. In Table 1, the authors should provide the P value of comparison between
patients with HBV DNA reduction # or > 5 log10copies/ml at week 24 in the HBV
DNA kinetics study.
8. In Table 4, the title describes “….telbivudine treatment in HBeAg-positive
Taiwanese patients….”. However, this table also includes HBeAg-negative
patients.
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests'
Please review this paper.
user
Reviewer's report
Title:Efficacy of telbivudine in Taiwanese chronic hepatitis B patients compared
with GLOBE extension study and predicting treatment outcome by HBV DNA
kinetics at Week 24
Version: 1Date:6 July 2012
Reviewer: Jia-Horng Kao
Reviewer's report:
General Comments:
At present, there are two major categories of chronic hepatitis B (CHB) therapy:
standard or pegylated interferon alpha and nucleos(t)ide analogues (NAs),
including lamivudine (LAM), telbivudine (LdT), entecavir (ETV), adefovir dipivoxil
(ADV) and tenofovir disoproxil furamate (TDF). Although the new generation NAs
such as ETV and TDF are potent and effective with less drug resistance for the
treatment of CHB, the majority of CHB patients require long-term treatment to
maintain on-treatment viral suppression. Previous pivotal trials showed that
HBeAg-positive or –negative CHB patients treated with LdT had a significantly
greater reduction of serum HBV DNA level than those treated with LAM.
Nevertheless, like LAM, virological response to LdT decreases over time due to
the emergence of drug resistance to LdT. In this sub-study of GLOBE trial, Hsu
et al. investigated the results of 4-year LdT treatment in Taiwanese patients.
They found that the long-term efficacy of LdT in Taiwanese patients was
consistent with the GLOBE study. They also found a reduction of HBV DNA
levels > 5 log 10 copies/ml at week 24 could predict favorable outcomes in
patients with high baseline HBV DNA levels. Although their data are interesting
and potentially important, the major limitations include small patient number and
the lack of multivariate analysis to determine the predictors of treatment
outcomes. In addition, several issues are worthy of attention.
Specific Comments:
1. The major limitations are small patient number and the lack of multivariate
analysis to determine factors predictive of treatment outcomes. These flaws
make their conclusions less convincing.
2. In HBV DNA kinetics study, the baseline HBV DNA level of patients with HBV
DNA reduction # 5 log10 copies/ml at week 24 was lower than those with HBV
DNA reduction > 5 log10copies/ml at week 24. It is thus interesting to know which
is the predictor of favorable treatment outcome, baseline HBV DNA, or HBV DNA
reduction > 5 log10copies/ml at week 24, or undetectable HBV DNA at week 24?
To this end, multivariate analysis should be performed to answer this important
issue.
3. In this study, Taiwanese patients seemed to have a lower cumulative HBeAg
seroconversion rate as well as the proportion of patients achieved undetectable
HBV DNA at Year 4 and bear a higher genotypic resistance rate than those in the
extension 2303 study. The authors might have a good explanation for the
discrepant results.
4. In this study, HBsAg kinetics during treatment was only analyzed in 6
HBeAg-positive patients. Because of small patient number, it is premature to
conclude that most Taiwanese patients had a rapid decline in HBsAg levels
during LdT treatment.
5. High HBsAg loss or seroconversion rate was observed in patients with a rapid
decline in HBsAg level from baseline to week 24. The authors should provide the
overall HBsAg loss/seroconversion rate in all Taiwanese patients. In addition, the
incidence of HBsAg loss or seroconversion in these patients is much higher than
previously reported data. Therefore, the authors should provide the data of HBV
DNA levels at the time of HBsAg loss.
6. The association of HBV genotype with response or resistance to NAs remains
unclear. Thus, the impact of HBV genotype on the response or resistance to LdT
therapy in Taiwanese patients needs to be addressed.
7. In Table 1, the authors should provide the P value of comparison between
patients with HBV DNA reduction # or > 5 log10copies/ml at week 24 in the HBV
DNA kinetics study.
8. In Table 4, the title describes “….telbivudine treatment in HBeAg-positive
Taiwanese patients….”. However, this table also includes HBeAg-negative
patients.
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests'
assistant