Effects of Sofosbuvir/Ledipasvir Therapy on Chronic Hepatitis C Virus Genotype 4, Infected Children of 3–6 Years of Age

Enas M. Kamal; Mortada El-Shabrawi; Hisham El-Khayat; Mostafa Yakoot; Yehia Sameh; Yasser Fouad; Dina Attia


Liver International. 2020;40(2):319-323. 

In This Article

Patients and Methods

Selection of Patients

This was a prospective, multicentre study. The study included 22 patients recruited from four clinical study sites: Faculty of Medicine of Cairo University, Faculty of Medicine, Beni-Suef University, Green Clinic Research Center and Minia Faculty of Medicine.

A total of 22 consecutive patients (mean age: 4.8 ± 0.9 years, male gender: n = 19 [86%] and weight: 14.5–23.4 kg) who fulfilled the inclusion criteria were included in this study.

Inclusion criteria were children aged between 3 and 6 years, with HCV RNA analysis by polymerase chain reaction (PCR) results of more than 1.000 IU/L.

Exclusion criteria were children older than 6 or younger than 3 years, viral load less than 1.000 IU/L, patients with associated comorbidities as hepatitis B virus infection, autoimmune hepatitis, Wilson's disease, any biliary disorder, haemolytic anaemia, or any malignancy or critical illness. Patients whom their parents refused to include them in the study. Four patients were excluded from the study; one patient with viral load lower than 1.000 IU/L, one patient had renal impairment and two patients, their parents refused to include them in the study.

All patients underwent laboratory assessment and transient elastography to evaluate their medical condition and advanced fibrosis and liver cirrhosis before the initiation of treatment. This study was performed in accordance with the Declaration of Helsinki after approval from the local ethical committee and written informed consent from patients' parents were obtained. All laboratory data and side effects were followed up on at Weeks 4, 8 and 12 and at 12 weeks after the end of treatment (sustained virologic response 12, SVR12). Parents were instructed to immediately contact their responsible doctor (who was required to always be available) if any serious side effects or other worrisome condition developed at any time during treatment.

Treatment Regimens

All patients received a combination of sofosbuvir 200 mg and ledipasvir 45 mg in a single oral daily dose if their weight was less than 35 kg. A generic form of the drug was provided by an Egyptian pharmaceutical company 'Pharco'. Parents were instructed about the method of intake and, in the case of difficult swallowing, that the tablet could be ground in juice, especially for intake by young children. Patients were randomly subdivided, according to a computer system, into two groups of treatment, an 8-week group (n = 11) and a 12-week group (n = 11).

Efficacy of the Treatment Regimens

Patients were followed up with using HCV RNA analysis for the assessment of response. The primary endpoint of this study was the loss of HCV RNA at the end of treatment (Weeks 8 and 12 for the 8- and 12-week groups, respectively). The secondary endpoint was the loss of HCV RNA at 12 weeks after the end of treatment (SVR12) for both groups. Virologic failure was defined as a reappearance of HCV RNA at any time point after disappearance during or after the end of treatment until SVR12.

Safety of the Treatment Regimens

All adverse effects were regularly recorded during treatment follow-up including at Weeks 4, 8 and 12 and at 12 weeks after the end of treatment. Serious side effects were defined as any hepatic decompensation, jaundice, ascites, lower limb oedema, hepatic encephalopathy, severe fatigue or loss of consciousness, severe diarrhoea or vomiting, bleeding from any of the body orifices, development of any extrahepatic malignancies, reduction in haemoglobin level below 10 g/dL and/or a requirement of hematopoietic factors, drop in the platelet count to below 50 × 103 mm/L or in the neutrophilic count to below 500 mm/L, drop in albumin level to less than 2.8 g/dL, and rise in bilirubin level to more than 1.5 mg/dL.

Laboratory Assessment

Routine laboratory tests performed at baseline (prior to treatment) and followed up at each visit (Weeks 4, 8, 12 and 12 weeks post-treatment included: haemoglobin level; total leucocytic count, neutrophilic count and platelet count; aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum bilirubin and albumin levels; international normalized ratio; and serum creatinine, alfa-fetoprotein level and hepatitis B virus surface antigen findings. During the follow-up visits, including at Weeks 4, 8 and 12 and at 12 weeks at the end of treatment, the laboratory data collected were haemoglobin level; total leucocytic count, neutrophilic count and platelet count; and aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum bilirubin and creatinine findings.

HCV Genotyping. HCV genotyping was done by direct sequencing of the 5' untranslated region (5'UTR) using RT-PCR-based assay (AmpliSens HCV-genotype-FRT PCR kit).

Statistical Analysis

Statistical analysis was performed using the Statistical Package for the Social Sciences version 22 software program (IBM Corp.). Quantitative values were expressed as means ± standard deviations. Qualitative data were expressed as proportions and percentages (with upper and lower confidence limits) were calculated the mean percent of response of all patients, patients in the 8-week group, and patients in the 12-week group, respectively.