Real life efficacy of ledipasvir/sofosbuvir in hepatitis C genotype 4-infected patients with advanced liver fibrosis and decompensated cirrhosis.

Limited clinical trial data has shown high efficacy of co-formulated ledipasvir/sofosbuvir (LDV/SOF) in the treatment of hepatitis C virus (HCV) genotype (GT)-4 infected cirrhotic patients. We assessed real-world safety and efficacy of LDV/SOF with or without ribavirin (RBV) in GT4-infected patients with compensated and decompensated cirrhosis. PATIENTS & METHODS: This observational cohort (n = 213) included GT4 treatment-naïve (59.6%) and -experienced (40.4%) patients with advanced fibrosis (F3, Metavir; n = 30), compensated (F4, n = 135) and decompensated cirrhosis (n = 48) treated for 12 (n = 202) or 24 weeks (n = 11) with LDV/SOF. RBV was dosed by physician discretion between 600-1200 mg daily. Patients with prior DAA failure were excluded from the analysis. The primary efficacy endpoint was sustained virologic response 12 weeks after treatment (SVR12) on an intention-to-treat analysis, and occurrence of serious adverse events (SAEs). RESULTS: The mean age of the overall cohort was 59.6 ±â€¯12.1 years and 125 (58.7) were female. Overall, 197 (92.5%) of the patients achieved SVR12, including 93.3% of F3 fibrosis, 93.3% of compensated cirrhotics and 89.6% of the decompensated cirrhotics (P = 0.686). Addition of RBV (68.5%) did not enhance efficacy (91.8% vs. 94.0% without RBV, P = 0.563), including in F3 fibrosis, compensated and decompensated cirrhosis (P > 0.05, for all). There was no difference in SVR12 rates with 24 and 12 weeks therapy (90.9% and 92.6%, respectively; P = 0.586). Treatment failure (n = 16) was mostly related to relapse (n = 11), while on-treatment death (n = 3) and breakthrough (n = 2) comprised a minority. SAEs occurred in 9 (4.2%) patients requiring early treatment discontinuation in 4 (3 on-treatment deaths and 1 pregnancy). CONCLUSION: LDV/SOF therapy yielded high SVR12 rates in both compensated and decompensated cirrhotic GT4 patients. The addition of RBV to this regimen did not improve efficacy. The safety profile of this regimen was comparable with that reported for other HCV genotypes.

High Efficacy of ombitasvir/paritaprevir/ritonavir plus dasabuvir in hepatitis C genotypes 4 and 1-infected patients with severe chronic kidney disease.

BACKGROUND & AIMS: Limited data have shown high efficacy of co-formulated ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) in the treatment of hepatitis C virus (HCV) genotype (GT)-4, and combined with dasabuvir (DSV) in GT1 patients, with chronic kidney disease (CKD) stages 4-5 (<30 mL/min/1.73 m2 ). We assessed real-world safety and efficacy of OBV/PTV/r ± DSV in GT1- and 4-infected patients. METHODS: In this observational cohort (n = 67), we enrolled stages 4-5 CKD treatment-naïve or Peginterferon/RBV-experienced GT4-infected patients (n = 32) treated for 12-24 weeks with OBV/PTV/r ± RBV, and plus DSV in GT1 patients (n = 35, including 3 with GT1/4 co-infection). RBV was dosed by physician discretion between 200 mg weekly and 200 mg daily. Primary endpoints were SVR12, calculated on intention-to-treat (ITT) basis, and occurrence of serious adverse events. RESULTS: The mean age of the cohort was 45.7 ± 12.7 years, 50.7% were females, 20.9% had cirrhosis, 35.8% were treatment-experienced and 97% were on haemodialysis. Three patients (F4) received 24-week treatment, 2 with GT4, and 1 with GT1a; and 19.4% were treated without RBV, including 9 GT1, and 4 GT4. Overall, 65 (97.1%) patients achieved SVR12, including 100% of those with a post-treatment follow-up (modified ITT analysis). Of the two patients without SVR12, one died from sepsis-related complications and the other from a myocardial infarction 2 weeks after completing therapy. Grades 3-4 anaemia occurred in 8.9%. CONCLUSION: A 12-week regimen of OBV/PTV/r ± DSV with or without RBV is highly effective with a favourable safety profile amongst GT4 and GT1 patients with CKD stages 4-5. SVR12 rates were high regardless of patient characteristics.