Reviewer's report
Title:Early virological response is a predictor of treatment response in
sofosbuvir-based combination therapy of chronic hepatitis c in a multi-center
"real-life" cohort
Version:1Date:7 May 2015
Reviewer: Christoph Höner zu Siederdissen
Reviewer's report:
The authors assessed the safety and efficacy of Peg-IFN/RBV/SOF and
SOF/RBV in 118 patients from 4 sites with various genotypes in a real-world
scenario. They found the SVR12 rates to be slightly lower in comparison with
phase 3 trials and identified the early treatment response as a potential predictor
for the treatment response in HCV genotype 1. The manuscript is well written
and helps to assess the value of the novel DAA therapies in clinical practice.
Some issues should be addressed:
Major Compulsory Revisions
Methods:
a) The selection process to include patients into the study should be described
more precisely. Were patients included on a consecutive basis between January
and June 2014? Were any patients excluded from entering the study? The
inclusion/exclusion criteria should be stated.
b) Were patients with decompensated cirrhosis included?
c) The sensitivity of quantification of HCV RNA differs between different tests (J
Clin Microbiol. 2015 Sarrazin et al., J Clin Virol. 2014 Schønning K et al and
others). It should be mentioned which test was used for HCV RNA quantification
and if the same test was used in all 4 centers.
Results:
d) Did some patients switch from Peg-IFN/RBV/SOF to SOF/RBV or had to
reduce the dosage of Peg-IFN due to side effects? If these events occurred,
were they more prominent in the group with later relapse?
Discussion:
e) The authors propose that the early virological response is a predictor for
treatment response (line 221,...).. The authors should discuss, if different assays
may have an influence on the predictive value of the early treatment response.
f) The finding that treatment experienced genotype 3 infected patients with
cirrhosis have SVR rates above the results in the phase 2/3 studies
(VALENCE/LONESTAR) with SOF/RBV should be discussed in more detail,
especially as the findings of the phase 2/3 studies could be reproduced in
recenet trials (BOSON study). What factors may have contributed to the
favorable results in the present cohort?
Minor Essential Revisions
Discussion: The authors compare their findings with results from the phase 2/3
studies of the antiviral regimens and discuss discrepancies. Some minor
adjustments to the discussion section should be made:
a) With current therapies SVR (SOF/LDV or PTV/r/OBV/DSV) rates in HCV
genotype 1 are > 95% (including treatment experienced patients and patients
with cirrhosis), thus, genotype 3 infected patients or special populations (renal
insufficiency, decompensated cirrhosis) are considered difficult-to-treat patients.
The statement from line 185 - 187 should be adjusted accordingly.
b) The predictive value of early treatment response as a predictor for SVR was
not stated as the primary goal of this manuscript. Furthermore the manuscript is
based on retrospective data, thus the title may be misleading and should be
rephrased to be more cautious (i.e. Early treatment response as a predictor
......... / may predict........)
Discretionary Revisions
a) Methods: SVR12 is generally accepted as an endpoint. The sentence in line
93 can be omitted.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Reviewer's report
Title:Early virological response is a predictor of treatment response in
sofosbuvir-based combination therapy of chronic hepatitis c in a multi-center
"real-life" cohort
Version:1Date:7 May 2015
Reviewer: Christoph Höner zu Siederdissen
Reviewer's report:
The authors assessed the safety and efficacy of Peg-IFN/RBV/SOF and
SOF/RBV in 118 patients from 4 sites with various genotypes in a real-world
scenario. They found the SVR12 rates to be slightly lower in comparison with
phase 3 trials and identified the early treatment response as a potential predictor
for the treatment response in HCV genotype 1. The manuscript is well written
and helps to assess the value of the novel DAA therapies in clinical practice.
Some issues should be addressed:
Major Compulsory Revisions
Methods:
a) The selection process to include patients into the study should be described
more precisely. Were patients included on a consecutive basis between January
and June 2014? Were any patients excluded from entering the study? The
inclusion/exclusion criteria should be stated.
b) Were patients with decompensated cirrhosis included?
c) The sensitivity of quantification of HCV RNA differs between different tests (J
Clin Microbiol. 2015 Sarrazin et al., J Clin Virol. 2014 Schønning K et al and
others). It should be mentioned which test was used for HCV RNA quantification
and if the same test was used in all 4 centers.
Results:
d) Did some patients switch from Peg-IFN/RBV/SOF to SOF/RBV or had to
reduce the dosage of Peg-IFN due to side effects? If these events occurred,
were they more prominent in the group with later relapse?
Discussion:
e) The authors propose that the early virological response is a predictor for
treatment response (line 221,...).. The authors should discuss, if different assays
may have an influence on the predictive value of the early treatment response.
f) The finding that treatment experienced genotype 3 infected patients with
cirrhosis have SVR rates above the results in the phase 2/3 studies
(VALENCE/LONESTAR) with SOF/RBV should be discussed in more detail,
especially as the findings of the phase 2/3 studies could be reproduced in
recenet trials (BOSON study). What factors may have contributed to the
favorable results in the present cohort?
Minor Essential Revisions
Discussion: The authors compare their findings with results from the phase 2/3
studies of the antiviral regimens and discuss discrepancies. Some minor
adjustments to the discussion section should be made:
a) With current therapies SVR (SOF/LDV or PTV/r/OBV/DSV) rates in HCV
genotype 1 are > 95% (including treatment experienced patients and patients
with cirrhosis), thus, genotype 3 infected patients or special populations (renal
insufficiency, decompensated cirrhosis) are considered difficult-to-treat patients.
The statement from line 185 - 187 should be adjusted accordingly.
b) The predictive value of early treatment response as a predictor for SVR was
not stated as the primary goal of this manuscript. Furthermore the manuscript is
based on retrospective data, thus the title may be misleading and should be
rephrased to be more cautious (i.e. Early treatment response as a predictor
......... / may predict........)
Discretionary Revisions
a) Methods: SVR12 is generally accepted as an endpoint. The sentence in line
93 can be omitted.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Please review this paper.
user
Reviewer's report
Title:Early virological response is a predictor of treatment response in
sofosbuvir-based combination therapy of chronic hepatitis c in a multi-center
"real-life" cohort
Version:1Date:7 May 2015
Reviewer: Christoph Höner zu Siederdissen
Reviewer's report:
The authors assessed the safety and efficacy of Peg-IFN/RBV/SOF and
SOF/RBV in 118 patients from 4 sites with various genotypes in a real-world
scenario. They found the SVR12 rates to be slightly lower in comparison with
phase 3 trials and identified the early treatment response as a potential predictor
for the treatment response in HCV genotype 1. The manuscript is well written
and helps to assess the value of the novel DAA therapies in clinical practice.
Some issues should be addressed:
Major Compulsory Revisions
Methods:
a) The selection process to include patients into the study should be described
more precisely. Were patients included on a consecutive basis between January
and June 2014? Were any patients excluded from entering the study? The
inclusion/exclusion criteria should be stated.
b) Were patients with decompensated cirrhosis included?
c) The sensitivity of quantification of HCV RNA differs between different tests (J
Clin Microbiol. 2015 Sarrazin et al., J Clin Virol. 2014 Schønning K et al and
others). It should be mentioned which test was used for HCV RNA quantification
and if the same test was used in all 4 centers.
Results:
d) Did some patients switch from Peg-IFN/RBV/SOF to SOF/RBV or had to
reduce the dosage of Peg-IFN due to side effects? If these events occurred,
were they more prominent in the group with later relapse?
Discussion:
e) The authors propose that the early virological response is a predictor for
treatment response (line 221,...).. The authors should discuss, if different assays
may have an influence on the predictive value of the early treatment response.
f) The finding that treatment experienced genotype 3 infected patients with
cirrhosis have SVR rates above the results in the phase 2/3 studies
(VALENCE/LONESTAR) with SOF/RBV should be discussed in more detail,
especially as the findings of the phase 2/3 studies could be reproduced in
recenet trials (BOSON study). What factors may have contributed to the
favorable results in the present cohort?
Minor Essential Revisions
Discussion: The authors compare their findings with results from the phase 2/3
studies of the antiviral regimens and discuss discrepancies. Some minor
adjustments to the discussion section should be made:
a) With current therapies SVR (SOF/LDV or PTV/r/OBV/DSV) rates in HCV
genotype 1 are > 95% (including treatment experienced patients and patients
with cirrhosis), thus, genotype 3 infected patients or special populations (renal
insufficiency, decompensated cirrhosis) are considered difficult-to-treat patients.
The statement from line 185 - 187 should be adjusted accordingly.
b) The predictive value of early treatment response as a predictor for SVR was
not stated as the primary goal of this manuscript. Furthermore the manuscript is
based on retrospective data, thus the title may be misleading and should be
rephrased to be more cautious (i.e. Early treatment response as a predictor
......... / may predict........)
Discretionary Revisions
a) Methods: SVR12 is generally accepted as an endpoint. The sentence in line
93 can be omitted.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests.
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