Sofosbuvir‐based regimens for the treatment of chronic hepatitis C in severe renal dysfunction

Abstract

Sofosbuvir (SOF) is a nonstructural 5B polymerase inhibitor with activity in all hepatitis C virus (HCV) genotypes and is the backbone of many anti‐HCV drug regimens. SOF is converted into inactive metabolites that undergo renal excretion. Patients with an estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73 m2 may experience increased drug exposure and thus potential toxicities along with decreased efficacy due to dose reduction or drug discontinuation. This is a single‐center study evaluating safety and effectiveness of SOF‐based regimens in patients with severe renal dysfunction, defined as eGFR <30 mL/minute/1.73 m2, including those receiving concurrent hemodialysis. Data were collected from patients with HCV and severe renal dysfunction who started full‐dose (400 mg) SOF‐based antiviral therapy ± ribavirin between April 2014 and February 2016. Medical records were reviewed for demographics, medical history, laboratory, radiologic imaging, echocardiography, transplant status, and liver pathologic findings. Twenty‐nine patients were identified; 12 had cirrhosis and 4 of those had decompensated cirrhosis. Fourteen patients had undergone transplantation of liver and/or kidney and were on calcineurin inhibitors, with 42% requiring dose increases or decreases while on therapy. All patients attained viral suppression on treatment, and 97% had a sustained viral response at 12 weeks posttreatment. There were no early treatment discontinuations. One death occurred posttreatment from a non‐ST elevation myocardial infarction in a patient with a history of coronary artery disease and ischemic cardiomyopathy. Conclusion: SOF‐based regimens appear safe in a broad range of patients with severe renal dysfunction, including those with decompensated cirrhosis and liver transplant. To confirm these retrospective findings, prospective studies that include SOF and SOF metabolite measurements coupled with prospective serial monitoring of electrocardiograms and echocardiograms are needed. (Hepatology Communications 2017;1:248‐255)

Sofosbuvir‐containing regimens are safe and effective in the treatment of HCV patients with moderate to severe renal impairment

“…This high SVR rate may be related to the observation that SOF produces similar concentrations of active intracellular metabolites independent of renal function . Similarly, high SVR rates were reported by Cox‐North et al who studied the safety and effectiveness of full dose SOF in 29 patients with severe renal dysfunction . Borgia et al also reported a high SVR rate of 95% in his phase II study on 59 patients with chronic HCV and ESRD undergoing haemodialysis or peritoneal dialysis who received open‐label full dose sofosbuvir/velpatasvir for 12 weeks .…”

“…In real‐life experience, there are reports of deterioration of renal function on SOF‐based therapy . On the other hand, several studies have demonstrated the safety of sofosbuvir in patients with severe CKD …”

“…Though smaller doses of the drug (200 mg/d or 400 mg on alternate day) were used by some investigators, several authors showed lower SVR rates with such doses . On the other hand, high efficacy and safety of full dose SOF‐containing regimens in patients with severe renal impairment were also demonstrated by many investigators …”

Human Immunodeficiency Virus-Hepatitis C Virus Coinfection: A Review on Necessity of Dietary Compounds for Antiretroviral Therapy

“…The use of anti-HCV PI drugs, boceprevir, and telaprevir in coinfected persons seems to illustrate a greater antiviral efficacy within the HIV/HCV coinfected population [43]. Different combination regimens reduce the risk of liver-related complications, sustained virological rates between 27% and 44% [5,44]. There is no cure for the HIV which causes AIDS, but a combination of drugs can keep the virus away from replicating and damaging the immune system [33].…”

Editorial: is sofosbuvir‐based therapy suitable for patients with advanced chronic kidney disease?

“…Another analysis reported the results of patients with eGFR <30 mL/min/1.7 m 2 who received SOF. All patients completed treatment, 97% achieved SVR, with 90% having unchanged renal function, four patients had improved renal function, with two discontinuing haemodialysis …”