Effects of sofosbuvir/ledipasvir therapy on chronic hepatitis C virus genotype 4, infected children of 3-6 years of age.

BACKGROUND & AIMS: Treatment of children aged 3-6 genotype 4 is still limited by the interferon side effects. We aimed in this study to evaluate the effectiveness and safety of sofosbuvir/ledipasvir in children (3-6 years) genotype 4 chronic HCV-infected patients. METHODS: In total, 22 consecutive chronic HCV-infected patients (mean age 4.8 ± 0.9years, 19 males) were included in this prospective study. All patients received sofosbuvir 200 mg/ledipasvir 45 mg in a single oral daily dose. Patients were randomly subdivided into two groups according the duration of treatment into 8 and 12 weeks. All the clinical and laboratory data were collected. All the side effects were recorded from the patients or their parents. Follow-up were made at Week 4, 8 and 12 and 12 weeks after the end of treatment (SVR12). RESULTS: The overall SVR12 rate was 100%. At Week 4, 9/11 patients in the 12-week group (81.8%; 95% CI: 52.3%-94.7%) achieved virologic negativity, vs 10/11 (90.9%; 95% CI: 62.3%-98.4%) in the 8-week group. At Week 8, 10/11 (90.8%; 95% CI: 62.3%-98.4%) in the 12-week group vs 11/11 (100%; 95% CI: 74.1%-100%) in the 8-week group were virologically negative. The reported side effects were cough, abdominal pain, nausea, vomiting and diarrhoea especially early in the treatment. The main complaint was difficulty in swallowing the tablets in the youngest patient at the beginning of the course of treatment. All patients were compliant to treatment. CONCLUSION: Sofosbuvir/ledipasvir combination is safe and tolerable in the chronic infected HCV genotype 4 infected children (3-6 years). The 8-week treatment duration is similarly effective as the 12-week duration.

Retreatment of chronic hepatitis C virus genotype-4 patients after non-structural protein 5A inhibitors' failure: efficacy and safety of different regimens.

BACKGROUND: Nonstructural protein 5A (NS5A) is an important regimen for the treatment of chronic hepatitis C virus (HCV) genotype-4 infected patients. Retreatments for NS5A virologic failure are limited. The aim of this study is to provide real-life data regarding the effectiveness and safety of retreatment with different regimens after NS5A regimen virologic failure in GT4 patients. PATIENTS AND METHODS: A total of 524 HCV patients (mean age 48 ± 11 years, 71% males), with virologic failure to sofosbuvir+daclatasvir, n = 450 and sofosbuvir/ledipasvir, n = 74 were included in this study. Patients were retreated with sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin, n = 278 and sofosbuvir + simeprevir + daclatasvir + ribavirin, n = 246. Response was evaluated 12 weeks after the end of treatment (SVR12). RESULTS: Overall, SVR12 was 95.2% [95% confidence interval (CI) 93.3%-97.1%]. In sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin and sofosbuvir + simeprevir + daclatasvir + ribavirin, SVR12s were 94.9% (95% CI 92.5%-97.4%) and 95.5% (95% CI 92.8%-98%), respectively. In liver cirrhosis patients, SVR12s were 96.4% (95% CI 90.7%-100%) and 98% (95% CI 94.9%-100%), respectively. Relapse in the sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin was n = 14 patients, and n = 11 patients in sofosbuvir + simeprevir + daclatasvir + ribavirin. Three patients developed hepatic encephalopathy, haematemesis, lower limb oedema, and one patient died in the SOF + OBV/PTV/RTV + RIB. In the sofosbuvir + simeprevir + daclatasvir + ribavirin, three patients developed hepatocellular carcinoma and one patient died. No treatment discontinuation due to anaemia. CONCLUSION: Salvage treatment for NS5A-treatment failure is effective and well tolerated in genotype-4 patients, in both noncirrhotic and compensated cirrhotic groups.

Effectiveness of 8-week sofosbuvir/ledipasvir in the adolescent chronic hepatitis C-infected patients.

BACKGROUND: The sustained virological response (SVR) rate for the 12-week sofosbuvir (SOF)/ledipasvir (LVD) treatment of adolescent genotype-4 patients is high. The aim of this study is to evaluate 8 versus 12-week treatment efficacy and safety in adolescent genotype-4 patients. PATIENTS AND METHODS: In total, 157 chronic hepatitis C-infected adolescent patients (mean age 14±2 years, 62% males) were included in this study. All patients received a morning dose of SOF (400 mg)/LVD (90 mg) as a single tablet for 8 and 12 weeks. Laboratory and biochemical monitoring were performed at weeks 4 and 8, end of treatment (8/12) and 12 weeks after the end of treatment (SVR12). RESULTS: In total, SVR12 was 98% [95% confidence interval (CI): 96-100] for all treated patients. For patients treated for 12 weeks, SVR12 was 97.6% (95% CI: 96-101) (82/84 patients), and 98.6% (95% CI: 93-101) (72/73) patients for those treated for 8 weeks. For both regimens, no serious adverse effects, treatment discontinuation or cases of death were detected. The main adverse effects for the 8-week patient group were fatigue (2.8%), headache (1.4%), nausea (1.4%) and epigastric tenderness (1.4%). For the 12-week-treated group, adverse events were epigastric tenderness (1.2%), nausea (1.2%), diarrhoea (2.4%) and rash (2.4%). Three patients were lost to follow-up: two were in the 12-week treatment group and one was in the 8-week group. All of them reached end of treatment but were lost before SVR12. No relapsers were observed in either group. CONCLUSION: Eight weeks of treatment of SOF/LVD combination is equally effective and safe as 12 weeks in adolescent genotype-4 patients.