Durability of Response in Children Treated With Pegylated Interferon alfa‐2a ± Ribavirin for Chronic Hepatitis C

Abstract

Objectives:No long-term data have been published on the durability of response following pegylated interferon (PegIFN) treatment in children with chronic hepatitis C (CHC). This prospective, multi-center, long-term follow-up (LTFU) study aimed to assess long-term durability of sustained virological response (SVR), long-term safety and tolerability, and the association between IL28B genotype and treatment response, in children previously treated with PegIFN alfa-2a ± ribavirin (RBV) in the PEDS-C trial.Methods: Ninety-three patients were assessed for enrollment and 38 enrolled in the study.Patients attended two study visits: 5 (mean 5.6; range 4.1 -6.6) and 6 (6.6; 5.1 -7.7) years after treatment cessation. Standardized medical history, physical examination and laboratory testing were done at these visits. Reminder telephone calls were conducted at 4 and 8 months after the initial visit. Results:The LTFU cohort was representative of the original PEDS-C cohort as both baseline and treatment characteristics were comparable. Of the 38 participants, 21 achieved SVR (responders) during the PEDS-C trial and 17 had not (non-responders). All 21 responders maintained undetectable HCV RNA during the LTFU (4.4 -7.0 years after achieving SVR) in contrast to the non-responders who demonstrated persistent viremia. IL28B CC genotype was associated with SVR (67%, vs. 30% in non-CC, p=0.028). Conclusion:Long-term durability of SVR is excellent following PegIFN alfa-2a treatment in children with CHC; SVR is higher in those with IL28B CC vs non-CC.Keywords: pediatric viral hepatitis; antiviral therapy; PEDS C study; long term follow up Copyright © ESPGHAN and NASPGHAN. All rights reserved.

The safety and effectiveness of ledipasvir−sofosbuvir in adolescents 12‐17 years old with hepatitis C virus genotype 1 infection

“…Despite well‐established guidelines for treating HCV in adults, there is no universal consensus on when or if to treat chronic HCV infection in children. Treatment of pediatric patients has been controversial as the current standard of care, pegylated interferon and weight‐based ribavirin, is associated with significant side effects, including growth impairment, and poor tolerability …”

“…Treatment of pediatric patients has been controversial as the current standard of care, pegylated interferon and weight-based ribavirin, is associated with significant side effects, including growth impairment, and poor tolerability. (10)(11)(12) In adults, all-oral, direct-acting HCV regimens offer the benefits of greater tolerability, improved response rates, fewer adverse events, easier administration, and shorter duration relative to pegylated interferon and ribavirin. (23) Multiple direct-acting HCV regimens are available for adults with HCV genotype 1 infection.…”

“…(3)(4)(5) Some children with chronic HCV may progress to develop hepatocellular carcinoma (6,7) or end-stage liver disease requiring liver transplantation. (8,9) In addition, because of side effects, poor tolerability, and the relatively low likelihood of success associated with pegylated interferon and ribavirin treatment, (10)(11)(12) it has been suggested that most children with chronic HCV infection should defer treatment until interferon-free regimens are available. (2) The prevalence of HCV in children varies globally, with estimates of 0.05%-0.36% in the United States and Europe (13) and up to 5.8% in regions of Africa.…”

Sofosbuvir and ribavirin in adolescents 12‐17 years old with hepatitis C virus genotype 2 or 3 infection

“…In pooled data from five studies, 93% of 73 children with HCV genotype 2 or 3 achieved sustained virologic response with 24 weeks of peginterferon and ribavirin . Response is durable, as indicated by a follow‐up study of 21 responders 4‐7 years after treatment . However, because of the potential for tolerability issues and growth impairment with peginterferon and ribavirin, there is no universal consensus on when or if to treat chronic HCV infection in children with these agents.…”

Hepatitis C virus infection in children and adolescents

“…Several studies have suggested that certain factors may predict a more favorable response to PEG‐IFN/RBV therapy, including host characteristics, such as the interleukin 28B polymorphisms, having genotype 2 or 3, and mode of transmission (iatrogenic versus vertical transmission) 114, 119, 120, 121, 122. Ultimately, the current standard of care in the treatment of HCV‐infected children with IFN and RBV regimens with their well‐documented toxicities, inconvenient modes of administration (subcutaneous IFN injections), longer durations of treatment, and poor overall efficacy often leaves pediatric hepatologists searching for alternatives.…”