bms-790052 and Renal-Insufficiency

Sofosbuvir is not recommended in persons with estimated glomerular filtration rate (eGFR) <30 mL/min. We report the results of treatment with an off-label 8-week regimen of daclatasvir and half-dose sofosbuvir in patients with acute infection with hepatitis C virus ( HCV) and eGFR <30 mL/min.. Clinic records were searched to identify treatment-naïve, noncirrhotic adults with acute hepatitis C (HCV viremia and a ≥10-fold elevation of serum alanine aminotransferase activity) and eGFR <30 mL/min, who had been treated with a sofosbuvir-based regimen. Treatment response was assessed using serum HCV RNA testing at 4 weeks of treatment, end of the 8-week treatment and 12 weeks after stopping treatment.. Of the 31 patients with acute hepatitis C, 27 [median age (range): 36 (18-74) years; 20 (74%) male] were started on treatment with 200 mg sofosbuvir and 60 mg daclatasvir daily for 8 weeks, irrespective of HCV genotype. All the 27 completed the planned 8-week treatment. One patient died 10 weeks after completing the treatment of an unrelated cause. All the 27 patients had undetectable HCV RNA after 4 weeks of and at the end of treatment. At 12 weeks after completion of treatment, only one tested HCV RNA positive and 25 were negative, with sustained virological response rate of 25/27 (92.6%) and 25/26 (96.2%) on intention-to-treat and per-protocol basis, respectively.. Eight-week course of daclatasvir and half-dose sofosbuvir is effective for acute hepatitis C in patients with eGFR <30 mL/min and could be a useful alternative to costly, kidney-safe anti-HCV oral drugs in resource-constrained settings.

Topics: Adolescent; Adult; Aged; Antiviral Agents; Carbamates; Drug Therapy, Combination; Female; Genotype; Hepacivirus; Hepatitis C; Humans; Imidazoles; Male; Middle Aged; Pyrrolidines; Renal Insufficiency; Sofosbuvir; Treatment Outcome; Valine; Young Adult

Many of the treatment regimens available for hepatitis C include sofosbuvir. Unfortunately, sofosbuvir has not been recommended for use in patients with severe renal impairment leaving these group of patients with very few options. Nevertheless, there are many reports in which these patients have been treated with sofosbuvir-containing regiments without important adverse events. This study aims at determining the safety and effectiveness of a sofosbuvir-based treatment in patients with severe renal impairment, including those on hemodialysis.. We enrolled subjects with hepatitis C and estimated glomerular filtration rate under ml/min/1.73m. A total of 103 patients were enrolled from 13 centers. Seventy-five patients were on hemodialysis. Thirty-nine had cirrhosis and eight were decompensated. Fifty-three were Genotype 1, and 27 Genotype 3. Twenty-seven patients had history of previous failed interferon-based treatment. Three patients died in which cause of death was not related to treatment. Six patients were lost to follow-up. The remaining 94 patients all achieved SVR. No adverse events leading to discontinuation of medicine was observed.. The combination of sofosbuvir and daclatasvir is an effective and safe treatment for patients infected with all genotypes of hepatitis C who have severe renal impairment, including patients on hemodialysis.

Topics: Antiviral Agents; Carbamates; Drug Therapy, Combination; Female; Hepatitis C; Humans; Imidazoles; Liver Cirrhosis; Male; Pyrrolidines; Renal Dialysis; Renal Insufficiency; Safety; Severity of Illness Index; Sofosbuvir; Sustained Virologic Response; Treatment Outcome; Valine

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

Topics: Antiviral Agents; Carbamates; Chemical and Drug Induced Liver Injury; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Genotype; Hepacivirus; Hepatitis C, Chronic; Hospitals, University; Humans; Imidazoles; Isoquinolines; Japan; Pyrrolidines; Renal Insufficiency; Sulfonamides; Treatment Outcome; Valine

HCV infection in chronic hemodialysis patients is high, has a poor prognosis and high risk of renal graft failure, and requires nosocomial infection control measures. However, options of anti-HCV therapy in such patients are limited and unsatisfactory. In this study, we report effectiveness and safety of HCV-NS5A-inhibitor daclatasvir (DCV) and protease-inhibitor asunaprevir (ASV) combination therapy for hemodialysis patients with HCV infection.. This study was registered at the UMIN Clinical Trials Registry as UMIN000016355. Thirty-four dialysis patients were treated with DCV/ASV combination therapy between January 2015 and November 2015. Of those, 21 patients who were followed more than 12 weeks after treatment ended were included. We evaluated the 12-week sustained virologic response (SVR12) and adverse events during treatment.. Of the 21 patients, four had compensated liver cirrhosis and three had resistance-associated variant of NS5A (NS5A RAVs)-Y93H at baseline. Overall, total of 95.5 % (20/21) of the patients achieved SVR12. Of note, all patients with cirrhosis or NS5A RAVs achieved SVR12. One relapser patient at 4 weeks post-treatment had NS3 D168E RAVs at baseline. A total of 20 patients (95.5 %) completed the 24-week therapy. One patient discontinued treatment at week 12 due to ALT elevations and achieved SVR12.. DAV and ASV combination therapy for chronic hemodialysis patients with HCV infection was highly effective and well tolerated, even in elderly patients and patients with liver cirrhosis and NS5A-RAVs.

Topics: Aged; Antiviral Agents; Carbamates; Drug Therapy, Combination; Female; Hepatitis C, Chronic; Humans; Imidazoles; Isoquinolines; Male; Middle Aged; Prospective Studies; Pyrrolidines; Renal Dialysis; Renal Insufficiency; Sulfonamides; Valine

Topics: Anti-HIV Agents; Antiviral Agents; Area Under Curve; Carbamates; Coinfection; Darunavir; Diuretics; Drug Interactions; Hepatitis C, Chronic; HIV Infections; Humans; Imidazoles; Male; Middle Aged; Nitriles; Pyridazines; Pyrimidines; Pyrrolidines; Renal Insufficiency; Ritonavir; Treatment Outcome; Valine

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