The results of real-world practice with glecaprevir/pibrentasvir for the treatment of chronic hepatitis C virus infection genotypes 1 and 3 in adolescents aged 12 to 17 years in the Moscow region

Abstract

Rationale: The first direct anti-viral agents (DAVA) for the treatment of adolescents with chronic hepatitis C virus (HCV) infection have been approved quite recently, i. e. in 2017 worldwide and in 2019 in Russia. Currently, only few adolescents are treated worldwide, their proportion in the Russian Federation not exceeding 9 to 15%. The results of real-world practice with various DAVA regiments in adolescents aged 12 to 17 years could be useful to choose the strategies for local healthcare bodies. Aim: To evaluate the efficacy and safety of the fixed combination of glecaprevir and pibrentasvir (GLE/PIB) in adolescents aged 12 to 17 years with HCV infection genotypes (GT) 1 and 3 in the Moscow region. Materials and methods: We retrospectively analyzed the results of treatment of 32 adolescents (gender ratio 1:1) who were treated for HCV infection (GT1, 49.9% of the cases, GT3, 53.1%; F1 fibrosis according to the METAVIR scale, 37.5% of the patients, F2, 9.4%) with GLE/PIB during 2019 to 2022 within the Program of State-guaranteed free medical care to the citizens of the Moscow region. The treatment course lasted for 8 weeks in 31 treatment-nave patients and 16 weeks in one patient who had failed on interferon treatment. The information was extracted from medical files of the patients treated on the outpatient basis and from discharge letters from the day care unit. Concomitant diseases were diagnosed in 75% of the adolescents. Results: At week 4 of GLE/PIB treatment, HCV RNA was undetectable in 90.6% (95% confidence interval (CI) 75.098.0) of the patients, and alanine aminotransferase activity reached the reference interval in all patients (100%). The rate of sustained viral response at 12 week of therapy was 96.9% (95% CI 83.899.9), including 100% (95% CI 78.2100) in the GT1 patients and 94.1% (95% CI 71.399.9) in the GT3 patients. At week 24 after the GLE/PIB treatment had been finished, the rate of liver fibrosis according to METAVIR decreased from 46.9% to 12.5% (p 0.001). The lack of response to GLE/PIB in one patient with GT1 HCV appeared to be due to missed doses of the drug. GLE/PIB-related adverse events (headache, fatigue, nausea, and diarrhea) were rare and were recorded in 9.4% (95% CI 1.925.0) of the patients, whereas unrelated adverse events (acute respiratory infection symptoms) in 15.6% (95% CI 5.332.8) of the patients. All adverse events were mild, occurred at 23 weeks of the treatment and did not require additional pharmacological intervention. Conclusion: The results obtained indicate a high efficacy and safety profile of GLE/PIB for the treatment of chronic HCV infection in adolescents aged 12 to 17 years. They can be used by local healthcare authorities to choose the treatment regimens effective for all genotypes and most suitable for children.