Direct-acting Antivirals for Hepatitis C Virus in Patients on Maintenance Dialysis

Abstract

The frequency of hepatitis C virus (HCV) infection remains high in patients with chronic kidney disease (CKD) and plays a detrimental role in mortality in this population. According to the latest survey, the adjusted hazard ratio for HCV-positive versus HCV-negative patients on long-term dialysis was 1.12 (95% CI, 1.05 to 1.20) and 1.10 (95% CI, 0.98 to 1.22) for all-cause and cardiovascular mortality, respectively. An impairment on quality of life has also been documented in HCV-infected patients undergoing regular dialysis. Most clinicians have been so far reluctant to treat hepatitis C in patients with advanced CKD, due to concerns regarding low efficacy and safety of interferon-based regimens. The advent of all-oral, direct-acting antivirals (DAAs) has revolutionized treatment paradigms for HCV, including patients with other comorbidities such as CKD. Two combinations of DAAs have been recently approved for the treatment of HCV in advanced CKD: elbasvir/grazoprevir (evaluated in 1 randomized controlled trial) and ombitasvir/paritaprevir/ritonavir/dasabuvir with or without ribavirin (examined in some observational, single-arm studies). These antiviral combinations have provided high safety and efficacy (SVR12 rates >90%) in HCV-infected patients with stage 4-5 CKD. Sofosbuvir, a nucleotide analogue inhibitor of the HCV NS5B polymerase, is the cornerstone of most anti-HCV current regimens but is not currently recommended for patients with severe renal insufficiency (eGFR <30 mL/min per 1.73 m2). However, several small-sized studies have been published on the safety and efficacy of sofosbuvir-based regimens for patients with hepatitis C on maintenance dialysis; overall, the viral response was satisfactory (SVR12 rates ranging between 58% and 100%) with a few drug-related drop-outs. Studies are in progress to assess whether ribavirin-free antiviral combinations with novel DAAs are a viable option for patients with severe renal impairment and chronic HCV infection.

Treatment Outcomes for Patients Undergoing Hemodialysis with Chronic Hepatitis C on the Sofosbuvir and Daclatasvir Regimen

“…These studies did not use DAC as the second drug. The treatment outcome for HCV GT-3 was better than GT-1; the SVR achieved for GT-1 was similar to that reported for the region [14-15], whereby worsening CKD is associated with lower SVRs and viral elimination.…”

Prevalence of resistance-associated substitutions to direct-acting antiviral agents in hemodialysis and renal transplant patients infected with hepatitis C virus

“…These treatments became promising for both HD patients and RTx recipients, showing high sustained virological response (SVR) rates without considerably increasing adverse effects or renal graft rejection. 11 – 14 …”

Hepatitis C Treatment of Renal Transplant and Chronic Kidney Disease Patients: Efficacy and Safety of Direct-Acting Antiviral Regimens Containing Sofosbuvir

“…The treatment of hepatitis C in patients with CKD has been a challenge over the years; however, the arrival of DAAs has substantially increased the likelihood of cure in this group, with SRV rates similar to those observed in the general population (13)(14)(15) . Regarding the use of SOF, rates ranging from 67% to 87% have been reported for dialysis patients, which can reach 89.4% in stage 4 and 5 CKD but with some patients using half the recommended dose (200 mg/day), a fact that could lead to a decrease in the response.…”