Safety and Efficacy of Combined Sofosbuvir/Daclatasvir Treatment of Children and Adolescents With Chronic Hepatitis C Genotype 4

Tawhida Y. Abdel Ghaffar; Suzan El Naghi; Manal Abdel Gawad; Sarah Helmy; Aisha Abdel Ghaffar; Medhat Yousef; Mohamad Moafy

Disclosures

J Viral Hepat. 2019;26(2):263-270. 

In This Article

Abstract and Introduction

Abstract

Direct-acting antivirals have become available for treating chronic HCV (hepatitis C virus) infection in adults and, recently, in children at least 12 years old. Our aim was to investigate the safety and efficacy of combined sofosbuvir (SOF)/daclatasvir (DCV) for HCV Genotype 4 in children aged 8 to 18 years or weighing 17 kg or more. A total of 40 chronic HCV-infected, treatment-naïve children with well compensated livers were recruited from two sites. Patients received combined therapy of SOF (400 mg/d for patients weighing greater than 45 kg; 200 mg/d for patients weighing 17 to 45 kg) and DCV (60 mg/d for patients weighing greater than 45 kg; 30 mg/d for patients weighing 17 to 45 kg) for 12 weeks. They were followed up regularly by clinical examination and laboratory tests during treatment (weekly in the first month then monthly to the end of treatment), every 3 months for 6 months post-treatment, and at 48 weeks post-treatment. In our cohort, which included 45% of children below the age of 12 years (72.5% genotype 4 and 27.5% mixed genotype 4 and 1), end of treatment response (ETR) was 97.5%. Sustained virologic response for weeks 12 and 24 post-treatment (SVR12 and SVR24) were 97.5% and 95%, respectively, on an intention to treat basis, and 100% and 100% for those who completed the study protocol. Observed side effects were mild and none required drug cessation. Combined SOF/DCV was found to be effective and safe for treating HCV Genotype 4-infected children, 8 years of age and above.

Introduction

Viral hepatitis is estimated as the 7th leading cause of global mortality, with about 50% of these deaths caused by HCV and its complications.[1] Egypt was estimated to have the highest HCV prevalence rate in the world in 2013 and 5th highest number of HCV-infected individuals in 2017.[2,3] With a prevalence rate of 14.7% and treatment costs amounting to around 1.4% of the gross national product, the burden of HCV infection in Egypt is substantial.[4,5]

The prevalence of HCV infection in children is up to 0.4% in the United States and Europe and up to 6% in resource-limited countries, or 11 million infections worldwide.[6] All six HCV genotypes are implicated in paediatric populations.[7] Though comprehensive epidemiological reports on the global genotype distribution in children and adolescents are lacking, reported paediatric populations tend to demonstrate similar regional distribution patterns as those of adults.[7]

HCV GT-4 represents 12%-15% (15–18 million) of the total global chronic HCV infection.[8] Its distribution has traditionally been restricted to Egypt, Central Africa and the Middle East regions,[9] though recently it has also been found in the Caribbean and India.[3] GT-4, and subtype 4a in particular, dominates the HCV epidemic in Egypt,[9,10] with most (>90%) isolates belonging to GT-4 (the remaining belonging to GT-1).[11]

Besides a wide range of side effects (bone marrow suppression with reduced cell counts, effects on growth, neurological disturbances and depression, among others), interferon (IFN)-containing regimens, the standard of HCV treatment before the era of DAAs, had success rates of only 50% in HCV GT-4 infected children.[12–14] Over the past few years, IFN-sparing regimens for treating chronic HCV have become available.[15] They are characterized by high rates of SVR, short duration of treatment, increased tolerability, as well as room to tailor treatment according to the patients' individual needs due to the presence of multiple agents that can interrupt several stages of the HCV lifecycle.[16] Recently, the US Food and Drug Administration and the European Medicines Agency have both approved the use of sofosbuvir and the fixed-dose combination of sofosbuvir/ledipasvir for adolescents of 12 years of age and older, and this has been recommended by the recent EASL and AASLD HCV treatment guidelines.[17–19]

SOF is a pangenotypic nucleotide analogue prodrug inhibitor of HCV NS5B polymerase.[20] SOF was approved for use under the brand name of Sovaldi in December 2013.[21] DCV, like ledipasvir, is an HCV NS5A replication complex inhibitor.[20] DCV was first approved in July 2013, originally only for GT-3.[21] The combined sofosbuvir/daclatasvir regimen has been recommended by EASL as a treatment of chronic HCV GT-4 infection in adults.[18] Previous studies revealed high efficacy of combined SOF/DCV in adults across different genotypes and subpopulations.[22–26] Several studies carried out in Egyptian adults with HCV infection showed similar results.[27–32]

The aim of this study was to investigate the safety and efficacy of combined therapy with SOF and DCV in HCV GT-4 chronic infection in children aged 8 to 18 years or weighing 17 kg or more.

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