title: Safety and efficacy of sofosbuvir-containing regimens in hepatitis C-infected patients with impaired renal function.
abstract: Renal clearance is the major elimination pathway for sofosbuvir (SOF). We assessed the safety and efficacy of SOF-containing regimens in patients with varying baseline estimated glomerular filtration rate (eGFR).
  
  
  
  HCV-TARGET database is a multicentre, longitudinal 'real-world' treatment cohort.
  
  
  
  A total of 1789 patients [genotypes 1 (72%), 2 (17%) 3 (9%), 4-6 (2%)] had baseline eGFR determination: 73 with eGFR≤45 (18 with eGFR≤30, 5 on dialysis) were compared to 1716 with eGFR>45 ml/min/1.73 m(2) . Patients with baseline eGFR≤45 vs. >45 differed in being female (55% vs. 36%), age ≥65 years (24% vs. 16%), Black race (22% vs. 12%), having cirrhosis with decompensation (73% vs. 24%) and being post-transplant (49% vs. 10%), all P < 0.05. All patients with eGFR≤45 were treated with SOF 400 mg/day (including those on haemodialysis) and had median starting ribavirin (RBV) dose of 800 mg (IQR: 400-1200). Sustained virologic response (SVR) frequencies were similar across eGFR groups, ranging from 82-83%. Patients with eGFR ≤45 more frequently experienced anaemia, worsening renal function and serious AEs (all P < 0.05), and these associations persisted when limiting analysis to RBV-free regimens. Patients with baseline eGFR≤30 and eGFR 31-45 had similar frequencies of efficacy and safety outcomes.
  
  
  
  Sustained viral clearance was achieved in 83% of patients with renal impairment (eGFR ≤45 ml/min/1.73 m(2) ) treated with SOF-containing regimens. However, these patients had higher rates of anaemia, worsening renal dysfunction and serious adverse events regardless of use of RBV. Patient with renal impairment require close monitoring and should be treated by providers extensively experienced with SOF-containing regimens.
authors.affiliation: University of California San Francisco, San Francisco, CA, USA.
authors.forename: Varun
authors.initials: V
authors.lastname: Saxena
authors.affiliation: Saint Louis University School of Medicine, St Louis, MO, USA.
authors.forename: Farrukh M
authors.initials: FM
authors.lastname: Koraishy
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Meghan E
authors.initials: ME
authors.lastname: Sise
authors.affiliation: Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Lim
authors.affiliation: University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Chung
authors.affiliation: Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Annmarie
authors.initials: A
authors.lastname: Liapakis
authors.affiliation: University of Florida, Gainesville, FL, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Nelson
authors.affiliation: University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Fried
authors.affiliation: University of California San Francisco, San Francisco, CA, USA.
authors.forename: Norah A
authors.initials: NA
authors.lastname: Terrault
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016208:Databases, Factual; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D005919:Glomerular Filtration Rate; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009656:North America; D012044:Regression Analysis; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology* / Q000628:therapy; D000069616:Simeprevir / Q000008:administration & dosage / Q000009:adverse effects; D000069474:Sofosbuvir / Q000008:administration & dosage* / Q000009:adverse effects; D000072230:Sustained Virologic Response; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D000069616:Simeprevir; D000069474:Sofosbuvir
keywords: decompensated cirrhosis; haemodialysis; liver transplantation; sustained virologic response