Skip to main content

Real-world efficacy and safety of glecaprevir/pibrentasvir in Japanese adolescents with chronic hepatitis C: a prospective multicenter study



Part 1 of the DORA study, a 2019 international clinical trial of glecaprevir and pibrentasvir (G/P) treatment in adolescents with chronic hepatitis C virus (HCV) infection, demonstrated high efficacy and safety. However, few reports have considered real-world experience with G/P treatment in adolescents with chronic HCV. The present prospective multicenter study assessed real-world efficacy and safety of G/P treatment in Japanese adolescents with chronic HCV.


Subjects between 12 and 17 years old who were treatment-naïve or previously managed with interferon-based regimens were prospectively enrolled and treated with G/P (300 mg/120 mg) once daily for 8 or 12 weeks. The primary efficacy endpoint was sustained virologic response at 12 weeks after treatment completion (SVR12). Adverse effects and laboratory abnormalities were assessed.


Twenty-five Japanese patients (15 female) were enrolled from 13 pediatric centers in Japan. Median age was 13 years (range 12–17). Numbers of patients with genotypes 1b, 2a, 2b, and 2b/1b were 6, 12, 6, and 1, respectively. Twenty-two were treatment-naïve, while three had experienced interferon-based treatments. All patients completed G/P treatment (24 for 8 weeks and 1 for 12). Twenty-four achieved SVR12 (96%). Most adverse events were mild. None were serious. G/P significantly decreased serum alanine aminotransferase, γ‐glutamyltransferase, and Wisteria floribunda agglutinin-positive Mac-2-binding protein concentrations. No negative effects on growth or maturation were apparent at 12 weeks.


Under real-world conditions, G/P treatment of Japanese adolescents with chronic HCV was highly efficacious and well tolerated.

This is a preview of subscription content, access via your institution.

Fig. 1



Adverse event


Alanine aminotransferase


Aspartate aminotransferase-to-platelet ratio index


Body mass index


Direct-acting antiviral




Glecaprevir and pibrentasvir


Hepatocellular carcinoma


Hepatitis C virus


Human immunodeficiency virus-1




Wisteria floribunda Agglutinin-positive Mac-2-binding protein




Resistance-associated substitution




Sustained virologic response at posttreatment week 12


  1. Polaris Observatory HCV Collaborators. Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study. Lancet Gastroenterol Hepatol. 2022;7:396–415.

    Article  Google Scholar 

  2. Schmelzer J, Dugan E, Blach S, et al. Global prevalence of hepatitis C virus in children in 2018: a modelling study. Lancet Gastroenterol Hepatol. 2020;5:374–92.

    Article  PubMed  Google Scholar 

  3. Tanaka J, Kurisu A, Ohara M, et al. Burden of chronic hepatitis B and C infections in 2015 and future trends in Japan: a simulation study. Lancet Reg Health West Pac. 2022;22:100428.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Mizuochi T, Takano T, Yanagi T, et al. Epidemiologic features of 348 children with hepatitis C virus infection over a 30-year period: a nationwide survey in Japan. J Gastroenterol. 2018;53:419–26.

    Article  PubMed  Google Scholar 

  5. Jonas MM, Rhee S, Kelly DA, et al. Pharmacokinetics, safety, and efficacy of glecaprevir/pibrentasvir in children with chronic HCV: part 2 of the DORA study. Hepatology. 2021;74:19–27.

    Article  CAS  PubMed  Google Scholar 

  6. Indolfi G, Fischler B, Gonzalez-Peralta RP, et al. Comparison of recommendations for treatment of chronic hepatitis C virus infection in children and adolescents: a position paper of the federation of international societies of pediatric gastroenterology, hepatology, and nutrition. J Pediatr Gastroenterol Nutr. 2020;70:711–7.

    Article  PubMed  Google Scholar 

  7. Indolfi G, Hierro L, Dezsofi A, et al. Treatment of chronic hepatitis c virus infection in children: a position paper by the hepatology committee of european society of paediatric gastroenterology, hepatology and nutrition. J Pediatr Gastroenterol Nutr. 2018;66:505–15.

    Article  PubMed  Google Scholar 

  8. Jonas MM, Squires RH, Rhee SM, et al. Pharmacokinetics, safety, and efficacy of glecaprevir/pibrentasvir in adolescents with chronic hepatitis C virus: part 1 of the DORA study. Hepatology. 2020;71:456–62.

    Article  CAS  PubMed  Google Scholar 

  9. Lampertico P, Carrión JA, Curry M, et al. Real-world effectiveness and safety of glecaprevir/pibrentasvir for the treatment of patients with chronic HCV infection: a meta-analysis. J Hepatol. 2020;72:1112–21.

    Article  CAS  PubMed  Google Scholar 

  10. Hayes CN, Imamura M, Tanaka J, et al. Road to elimination of HCV: clinical challenges in HCV management. Liver Int. 2022;42:1935–44.

    Article  PubMed  Google Scholar 

  11. Miura M, Maekawa S, Kadokura M, et al. Analysis of viral amino acids sequences and the IL28B SNP influencing the development of hepatocellular carcinoma in chronic hepatitis C. Hepatol Int. 2012;6:386–96.

    Article  PubMed  Google Scholar 

  12. Miura M, Maekawa S, Sato M, et al. Deep sequencing analysis of variants resistant to the non-structural 5A inhibitor daclatasvir in patients with genotype 1b hepatitis C virus infection. Hepatol Res. 2014;44:E360–7.

    Article  CAS  PubMed  Google Scholar 

  13. Isojima T, Kato N, Ito Y, et al. Growth standard charts for Japanese children with mean and standard deviation (SD) values based on the year 2000 national survey. Clin Pediatr Endocrinol. 2016;25:71–6.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Balistreri WF, Murray KF, Rosenthal P, et al. The safety and effectiveness of ledipasvir-sofosbuvir in adolescents 12–17 years old with hepatitis C virus genotype 1 infection. Hepatology. 2017;66:371–8.

    Article  CAS  PubMed  Google Scholar 

  15. Schwarz KB, Rosenthal P, Murray KF, et al. Ledipasvir-sofosbuvir for 12 weeks in Children 3 to <6 Years old with chronic hepatitis C. Hepatology. 2020;71:422–30.

    Article  CAS  PubMed  Google Scholar 

  16. Serranti D, Nebbia G, Cananzi M, et al. Efficacy of sofosbuvir/ledipasvir in adolescents with chronic hepatitis C genotypes 1, 3, and 4: A real-world study. J Pediatr Gastroenterol Nutr. 2021;72:95–100.

    Article  CAS  PubMed  Google Scholar 

  17. Uemura H, Uchida Y, Kouyama JI, et al. NS5A-P32 deletion as a factor involved in virologic failure in patients receiving glecaprevir and pibrentasvir. J Gastroenterol. 2019;54:459–70.

    Article  CAS  PubMed  Google Scholar 

  18. Singh AD, Maitra S, Singh N, et al. Systematic review with meta-analysis: impact of baseline resistance-associated substitutions on the efficacy of glecaprevir/pibrentasvir among chronic hepatitis C patients. Aliment Pharmacol Ther. 2020;51:490–504.

    Article  CAS  PubMed  Google Scholar 

  19. Sarrazin C. Treatment failure with DAA therapy: importance of resistance. J Hepatol. 2021;74:1472–82.

    Article  CAS  PubMed  Google Scholar 

  20. Izumi N, Takehara T, Chayama K, et al. Sofosbuvir-velpatasvir plus ribavirin in Japanese patients with genotype 1 or 2 hepatitis C who failed direct-acting antivirals. Hepatol Int. 2018;12:356–67.

    Article  PubMed  Google Scholar 

  21. Sezaki H, Suzuki F, Hosaka T, et al. Initial- and re-treatment effectiveness of glecaprevir and pibrentasvir for Japanese patients with chronic hepatitis C virus-genotype 1/2/3 infections. J Gastroenterol. 2019;54:916–27.

    Article  CAS  PubMed  Google Scholar 

  22. Tacke F, Klinker H, Boeker KHW, et al. Elevated liver enzymes predict morbidity and mortality despite antiviral cure in patients with chronic hepatitis C: data from the german hepatitis C-registry. Hepatol Commun. 2022.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Singh S, Facciorusso A, Loomba R, et al. Magnitude and kinetics of decrease in liver stiffness after antiviral therapy in patients with chronic hepatitis C: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2018;16:27-38.e4.

    Article  PubMed  Google Scholar 

  24. Ura K, Furusyo N, Ogawa E, et al. Serum WFA(+) -M2BP is a non-invasive liver fibrosis marker that can predict the efficacy of direct-acting anti-viral-based triple therapy for chronic hepatitis C. Aliment Pharmacol Ther. 2016;43:114–24.

    Article  CAS  PubMed  Google Scholar 

  25. Tajiri H, Suzuki M, Bessho K, et al. The role of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein in the assessment of fibrosis in children with chronic hepatitis C. Sci Rep. 2022;12:11205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Jonas MM, Balistreri W, Gonzalez-Peralta RP, et al. Pegylated interferon for chronic hepatitis C in children affects growth and body composition: results from the pediatric study of hepatitis C (PEDS-C) trial. Hepatology. 2012;56:523–31.

    Article  CAS  PubMed  Google Scholar 

Download references


The authors thank Shintaro Ogawa at the Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences for assisting with RASs analysis. We also thank all participating patients, their families, and their physicians for collaborating in data collection.


This work was supported by the Research Program on Hepatitis from the Japanese Agency for Medical Research and Development, AMED (22fk0210068h0003 and 22fk0210103).

Author information

Authors and Affiliations



Conceptualization: TM. Formal analysis and investigation: TM and YT. Resources: all authors. Supervision: YY and HT. Funding acquisition: TM, YT, and HT. Writing-original draft: TM. Writing-review and editing: all authors. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Tatsuki Mizuochi.

Ethics declarations

Conflict of interest

Tatsuki Mizuochi reports personal fees from AbbVie GK. Yasuhito Tanaka reports personal fees from Gilead Sciences Inc., Fujirebio Inc., and AbbVie GK; research grants from Gilead Sciences, Inc., Fujirebio Inc., AbbVie GK, and Board of Trustees of the Leland Stanford Junior University.

Ethics approval and consent to participate

This study protocol complied with the ethical guidelines of the Declaration of Helsinki and was approved by the Ethics Committee of Kurume University and its counterparts at other participating centers.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 23 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mizuochi, T., Iwama, I., Inui, A. et al. Real-world efficacy and safety of glecaprevir/pibrentasvir in Japanese adolescents with chronic hepatitis C: a prospective multicenter study. J Gastroenterol 58, 405–412 (2023).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: