Title: Efficacy and safety of glecaprevir and pibrentasvir in Japanese patients with hepatitis C
virus infection aged 75 years or older
Version: 1 Date: 12 Mar 2022
Reviewer's report:
Yuri Komaki et al. retrospectively compared the effectiveness and tolerance of glecaprevir/
pibrentasvir (GLE/PIB) in Japanese HCV patients with an age cutoff of 75 years. They
concluded that the overall performance of GLE/PIB in aged population was excellent and
comparable to non-aged group.
Major comment:
1. Please explain why patients with HCV genotype 3-6 infections were excluded from the
study, because GLE/PIB is an antiviral regimen with pangenotypic potency. In addition, why
patients with unknown HCV genotypes were included in the study, because they may have HCV
genotype 3-6 infections.
2. Although the authors claimed that patients with HCC were excluded from the study, patients
in Table 1 showed highly elevated AFP, which strongly suggested the presence of active HCC.
Furthermore, it was not clearly stated that patients with a history of HCC or active HCC were
excluded from the study. Please clarify these points.
3. The diagnosis of cirrhosis by laboratory tests in the section of “treatment regimen” was not
clear, and I assumed that it was diagnosed by FIB-4 index. Please explicate clearly and also
provide the cut-off value of FIB-4 in diagnosing cirrhosis. Table 1 should show the percentage
of patients with FIB-4 level with a cut-off value of FIB-4.
4. Section (follow-up): in patients who were treated with 8 weeks of GLE/PIB, no HCV RNA
test would present at on-treatment week 12. Please rewrite the description of the treatment and
follow-up programs with care.
5. It was unusual for patients who failed to NS3/NS5A agent should be treated with GLE/PIB
again since the package insert of GLE/PIB in the world recommended against the routine use
for such situation. One patient in the study who failed to DCV/ASV was retreated with GLE/
PIB and failed again, Please explicate the rationale of usage against global GLE/PIB package
insert. Please refer to Poordad, et al. (Hepatology 2018;67:1253-60) and discuss in detail about
why the authors treated such patient.
6. I was not clear about the adherence of GLE/PIB in two groups and how the adherence
would affect the responses. Please show the data. Please cite two related references and
discuss it (Brown A, et al. Liver Int 2020;40:778-86; Zamor PJ, et al. Am J Gastroenterol
2021;116:1896-904).
7. Please state clearly by a new Table about the clinical characteristics (baseline characteristics,
treatment duration, genotype etc…) of all the patients who failed to respond to GLE/PIB.
8. The authors nearly cited the papers from Japan and omitted global studies in the introduction.
Please be cautious about such presentation because the authors were prone to bias the literature
research. Please rewrite the introduction again and cite the paper as follows: Zeuzem S, et al.
N Engl J Med 2018;378:354-69; Brown Jr RS, et al. J Hepatol 2020;72:441-9; Asselah T, et
al. Clin Gastroenterol Hepatol 2018;16:417-26; Wyles D, et al. Hepatology 2018;67:514-23;
Asselah T, et al. Lancet Gastroenterol Hepatol 2019;4:45-51; Gane E, et al. N Engl J Med
2017;377:1448-55; Lawitz E. et al. Liver Int 2020;40:1032-41). Remove references No. 17, 18,
20 because they were not good representative studies.
Minor comment:
1. Numerous typos and grammatical errors are present in the manuscript. Please refer to English
editing to polish the text in the manuscript.
2. Several real-world studies which were relevant to the study should be cited in the
manuscript (Ogawa E, et al. Hepatol Res 2019;49:617-26; Naganuma A, et al. J Gastroenterol
2019;54:752-61; Sezaki H, et al. J Gastroenterol 2019;54:916-27; Liu CH, et al. Liver Int
2020;40:758-68).
Title: Efficacy and safety of glecaprevir and pibrentasvir in Japanese patients with hepatitis C
virus infection aged 75 years or older
Version: 1 Date: 12 Mar 2022
Reviewer's report:
Yuri Komaki et al. retrospectively compared the effectiveness and tolerance of glecaprevir/
pibrentasvir (GLE/PIB) in Japanese HCV patients with an age cutoff of 75 years. They
concluded that the overall performance of GLE/PIB in aged population was excellent and
comparable to non-aged group.
Major comment:
1. Please explain why patients with HCV genotype 3-6 infections were excluded from the
study, because GLE/PIB is an antiviral regimen with pangenotypic potency. In addition, why
patients with unknown HCV genotypes were included in the study, because they may have HCV
genotype 3-6 infections.
2. Although the authors claimed that patients with HCC were excluded from the study, patients
in Table 1 showed highly elevated AFP, which strongly suggested the presence of active HCC.
Furthermore, it was not clearly stated that patients with a history of HCC or active HCC were
excluded from the study. Please clarify these points.
3. The diagnosis of cirrhosis by laboratory tests in the section of “treatment regimen” was not
clear, and I assumed that it was diagnosed by FIB-4 index. Please explicate clearly and also
provide the cut-off value of FIB-4 in diagnosing cirrhosis. Table 1 should show the percentage
of patients with FIB-4 level with a cut-off value of FIB-4.
4. Section (follow-up): in patients who were treated with 8 weeks of GLE/PIB, no HCV RNA
test would present at on-treatment week 12. Please rewrite the description of the treatment and
follow-up programs with care.
5. It was unusual for patients who failed to NS3/NS5A agent should be treated with GLE/PIB
again since the package insert of GLE/PIB in the world recommended against the routine use
for such situation. One patient in the study who failed to DCV/ASV was retreated with GLE/
PIB and failed again, Please explicate the rationale of usage against global GLE/PIB package
insert. Please refer to Poordad, et al. (Hepatology 2018;67:1253-60) and discuss in detail about
why the authors treated such patient.
6. I was not clear about the adherence of GLE/PIB in two groups and how the adherence
would affect the responses. Please show the data. Please cite two related references and
discuss it (Brown A, et al. Liver Int 2020;40:778-86; Zamor PJ, et al. Am J Gastroenterol
2021;116:1896-904).
7. Please state clearly by a new Table about the clinical characteristics (baseline characteristics,
treatment duration, genotype etc…) of all the patients who failed to respond to GLE/PIB.
8. The authors nearly cited the papers from Japan and omitted global studies in the introduction.
Please be cautious about such presentation because the authors were prone to bias the literature
research. Please rewrite the introduction again and cite the paper as follows: Zeuzem S, et al.
N Engl J Med 2018;378:354-69; Brown Jr RS, et al. J Hepatol 2020;72:441-9; Asselah T, et
al. Clin Gastroenterol Hepatol 2018;16:417-26; Wyles D, et al. Hepatology 2018;67:514-23;
Asselah T, et al. Lancet Gastroenterol Hepatol 2019;4:45-51; Gane E, et al. N Engl J Med
2017;377:1448-55; Lawitz E. et al. Liver Int 2020;40:1032-41). Remove references No. 17, 18,
20 because they were not good representative studies.
Minor comment:
1. Numerous typos and grammatical errors are present in the manuscript. Please refer to English
editing to polish the text in the manuscript.
2. Several real-world studies which were relevant to the study should be cited in the
manuscript (Ogawa E, et al. Hepatol Res 2019;49:617-26; Naganuma A, et al. J Gastroenterol
2019;54:752-61; Sezaki H, et al. J Gastroenterol 2019;54:916-27; Liu CH, et al. Liver Int
2020;40:758-68).
Please review this paper.
user
Title: Efficacy and safety of glecaprevir and pibrentasvir in Japanese patients with hepatitis C
virus infection aged 75 years or older
Version: 1 Date: 12 Mar 2022
Reviewer's report:
Yuri Komaki et al. retrospectively compared the effectiveness and tolerance of glecaprevir/
pibrentasvir (GLE/PIB) in Japanese HCV patients with an age cutoff of 75 years. They
concluded that the overall performance of GLE/PIB in aged population was excellent and
comparable to non-aged group.
Major comment:
1. Please explain why patients with HCV genotype 3-6 infections were excluded from the
study, because GLE/PIB is an antiviral regimen with pangenotypic potency. In addition, why
patients with unknown HCV genotypes were included in the study, because they may have HCV
genotype 3-6 infections.
2. Although the authors claimed that patients with HCC were excluded from the study, patients
in Table 1 showed highly elevated AFP, which strongly suggested the presence of active HCC.
Furthermore, it was not clearly stated that patients with a history of HCC or active HCC were
excluded from the study. Please clarify these points.
3. The diagnosis of cirrhosis by laboratory tests in the section of “treatment regimen” was not
clear, and I assumed that it was diagnosed by FIB-4 index. Please explicate clearly and also
provide the cut-off value of FIB-4 in diagnosing cirrhosis. Table 1 should show the percentage
of patients with FIB-4 level with a cut-off value of FIB-4.
4. Section (follow-up): in patients who were treated with 8 weeks of GLE/PIB, no HCV RNA
test would present at on-treatment week 12. Please rewrite the description of the treatment and
follow-up programs with care.
5. It was unusual for patients who failed to NS3/NS5A agent should be treated with GLE/PIB
again since the package insert of GLE/PIB in the world recommended against the routine use
for such situation. One patient in the study who failed to DCV/ASV was retreated with GLE/
PIB and failed again, Please explicate the rationale of usage against global GLE/PIB package
insert. Please refer to Poordad, et al. (Hepatology 2018;67:1253-60) and discuss in detail about
why the authors treated such patient.
6. I was not clear about the adherence of GLE/PIB in two groups and how the adherence
would affect the responses. Please show the data. Please cite two related references and
discuss it (Brown A, et al. Liver Int 2020;40:778-86; Zamor PJ, et al. Am J Gastroenterol
2021;116:1896-904).
7. Please state clearly by a new Table about the clinical characteristics (baseline characteristics,
treatment duration, genotype etc…) of all the patients who failed to respond to GLE/PIB.
8. The authors nearly cited the papers from Japan and omitted global studies in the introduction.
Please be cautious about such presentation because the authors were prone to bias the literature
research. Please rewrite the introduction again and cite the paper as follows: Zeuzem S, et al.
N Engl J Med 2018;378:354-69; Brown Jr RS, et al. J Hepatol 2020;72:441-9; Asselah T, et
al. Clin Gastroenterol Hepatol 2018;16:417-26; Wyles D, et al. Hepatology 2018;67:514-23;
Asselah T, et al. Lancet Gastroenterol Hepatol 2019;4:45-51; Gane E, et al. N Engl J Med
2017;377:1448-55; Lawitz E. et al. Liver Int 2020;40:1032-41). Remove references No. 17, 18,
20 because they were not good representative studies.
Minor comment:
1. Numerous typos and grammatical errors are present in the manuscript. Please refer to English
editing to polish the text in the manuscript.
2. Several real-world studies which were relevant to the study should be cited in the
manuscript (Ogawa E, et al. Hepatol Res 2019;49:617-26; Naganuma A, et al. J Gastroenterol
2019;54:752-61; Sezaki H, et al. J Gastroenterol 2019;54:916-27; Liu CH, et al. Liver Int
2020;40:758-68).
assistant