ledipasvir and Renal-Insufficiency

Treatment of Hepatitis C virus (HCV) in patients with severe renal insufficiency is cumbersome as sofosbuvir is mainly excreted by the kidneys. There is paucity of data on the use of sofosbuvir and NS5A inhibitors in these patients. We hereby report our experience of treating chronic hepatitis C in patients with severe renal insufficiency with full dose sofosbuvir and NS5A inhibitors. Forty-seven patients with severe renal insufficiency (on dialysis n = 39, predialysis n = 8) with HCV infection were treated between December 2015-August 2017 with full dose sofosbuvir with ledipasvir or daclatasvir for 12/24 weeks depending on the genotype and the presence or absence of cirrhosis. The distribution of HCV genotype was genotype 1 in 32 (68.1%), genotype 3 in 13 (27.7%) and 4 in 2 (4.3%) patients. Among 12 (25.5%) patients with cirrhosis, 7 (14.9%) were decompensated with ascites. All patients had end of treatment response, and sustained viral response at 12 weeks was achieved in 45 (95.7%) patients. There was significant improvement in liver stiffness at 3 months after treatment (8.8 (3.8-42) to 7.1 (3.3-24.1) kPa; (P = 0.047)). There was no change in haemoglobin and eGFR with treatment in predialysis group (haemoglobin- 10.2 ± 1.5 g/dL vs 9.6 ± 1.3 g/dL, P = 0.44; eGFR- 19.8 ± 9.4 mL/min vs 17.9 ± 8.5 mL/min, P = 0.67). Therapy was very well accepted. Full dose sofosbuvir with NS5A inhibitors is a well tolerated and effective therapy for HCV infection in severe renal insufficiency.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Benzimidazoles; Carbamates; Female; Fluorenes; Genotype; Glomerular Filtration Rate; Hepacivirus; Hepatitis C, Chronic; Humans; Imidazoles; Male; Middle Aged; Pyrrolidines; Renal Insufficiency; Sofosbuvir; Treatment Outcome; Valine; Viral Nonstructural Proteins; Young Adult

DAA-based regimens for chronic hepatitis C infection encourage treatment of "difficult-to-treat" cohorts. This study investigated efficacy and safety of DAA-based regimens in HCV patients on dialysis or postkidney or liver/kidney transplantation. Twenty-five patients treated with DAA combinations were evaluated: 10 were on dialysis (eight: hemodialysis, two: peritoneal dialysis), eight were kidney transplant recipients, and seven were liver/kidney transplant recipients. Except for one patient treated with daclatasvir ([DCV]/60 mg/QD)/simeprevir ([SMV]/150 mg/QD), the others received sofosbuvir-based regimens ([SOF];400 mg/QD) combined with SMV:eight, DCV:13 or either ledipasvir ([LDV]90 mg/QD), ribavirin ([RBV];weight based) or pegylated interferon/RBV. HCV-RNA was determined by Abbott RealTime (LLOQ]:12 IU/ml) or Roche AmpliPrep/COBAS TaqMan assay (LLOQ:15 IU/ml); treatment response evaluated every 4 weeks, at the end of treatment, and 4 and 12 weeks thereafter. Twenty-four (96%) patients achieved SVR 12/24 (ITT-analysis). Mean treatment duration was 15.1 ± 5.1 weeks (±SD), and two patients terminated prematurely - both reached SVR12. Six patients were hospitalized due to complications of underlying disease. One patient achieved SVR24 but was re-infected (week 27). Kidney function remained stable; serum creatinine increased in only one patient - SOF was reduced to 400 mg/48 h. Treatment with DAA combinations in renally impaired HCV patients is highly effective and well tolerated. These findings call for further controlled trials and data from real-life cohorts.

Topics: Adult; Aged; Antiviral Agents; Benzimidazoles; Carbamates; Cohort Studies; Drug Therapy, Combination; Female; Fluorenes; Hepacivirus; Hepatitis C, Chronic; Humans; Imidazoles; Immunosuppressive Agents; Kidney; Kidney Function Tests; Kidney Transplantation; Liver; Liver Transplantation; Male; Middle Aged; Postoperative Period; Preoperative Period; Pyrrolidines; Renal Dialysis; Renal Insufficiency; RNA, Viral; Simeprevir; Sofosbuvir; Valine