Direct-acting antivirals for the treatment of chronic hepatitis C in patients with chronic kidney disease.

All-oral, direct-acting antivirals (DAAs) have significantly improved the efficacy and safety of chronic hepatitis C (CHC) treatment but their effectiveness and safety among patients with chronic kidney disease (CKD) remains poorly understood. Our aim was to assess the efficacy and safety of DAAs for treatment of CKD patients. The National Library of Medicine through PubMed was searched for studies evaluating the efficacy of DAAs for the treatment of patients with CKD stages 4 or 5, as defined by the Kidney Disease Outcomes Quality Initiative guidelines [i.e. glomerular filtration rate (GFR) 15-29 ml/min per 1.73 m2 and GFR <15 ml/min per 1.73 m2, respectively, or hemodialysis or peritoneal dialysis]. Randomized clinical trials (RCTs) and relevant cohort studies were included if they were published in English and included sustained viral response after 12 weeks (SVR12) as a primary or secondary endpoint. After applying inclusion and exclusion criteria, eight studies (one RCT and seven cohort studies) following 350 patients were selected. For patients with CKD stage 4 or 5, ± hemodialysis, the overwhelming majority of DAA regimens were well-tolerated and resulted in SVR12 rates of 90-100%. Most studies were small, with the exception of one RCT evaluating elbasvir and grazoprevir. Overall, treatment of CHC in patients with CKD is highly effective with SVR12 rates similar to those seen in patients without CKD and with acceptable adverse event profiles. In patients with hepatitis C virus (HCV) genotype (GT) 1a, 1b or 4 and Stage 4 or 5 CKD, the best evidence available is for the use of elbasvir and grazoprevir. This combination as well as the combination of paritaprevir/ritonavir/ombitasvir/dasabuvir for HCV GT-1b are recommended. More studies are needed to assess efficacy and adverse effects of DAAs and their impact on CKD patients and to fully elucidate the effect of curing CHC on the natural history and sequelae of renal disease in CHC patients with CKD.