Mr. Smith, a 58-year-old man with stage 4 chronic kidney disease, was referred to your clinic for management of chronic hepatitis C virus (HCV) infection. He describes his struggle to cope with months of intermittent fevers, headaches, and myalgia from interferon therapy and concern that his kidney function has declined since starting treatment with ribavirin 1 year ago. With the current treatment options, patients like Mr. Smith have struggled to find a balance between management of chronic kidney disease and HCV infection.
Patients with HCV are at high risk for chronic kidney disease and progression to end-stage renal disease. However, the only approved treatment regimen for HCV, interferon with ribavirin, carries a high risk of renal and systemic toxicity. In fact, few alternatives are available for patients with advanced chronic kidney disease and HCV genotype 1 or 4 infection and no interferon/ribavirin-free treatment options exist for patients with HCV genotypes 2, 3, 5 or 6 infections.
This week in NEJM, Gane et al. address the unmet need for effective, kidney-sparing treatment for HCV infection in the EXPEDITION-4 trial. This phase 3 multicenter, open-label study evaluated the efficacy and safety of daily oral combination therapy with glecaprevir and pibrentasvir (300 mg/120 mg) for 12 weeks in 104 adults with chronic HCV infection (genotypes 1-6), limited or no prior HCV treatment, and stage 4 or 5 chronic kidney disease. The primary outcome was sustained virologic response at 12 weeks after the end of the 12-week treatment period.
Among the study participants, 85 were on hemodialysis and 19 were not. Glecaprevir/pibrentasvir treatment resulted in a sustained virologic response in 98% of patients (95% CI, 95-100) and no virologic treatment failures during the initial 12-week treatment period. Notably, there was no significant change in mean estimated glomerular filtration rate (GFR) after 36 weeks in patients who were not on dialysis (mean change, -0.4 mL/min/1.73m2; P=0.53). Further, no serious adverse events related to glecaprevir/pibrentasvir were reported. The most common adverse events (in ≥10% of patients) were pruritus, fatigue and nausea.
Coformulated glecaprevir/pibrentasvir appears to be a useful treatment option for patients with HCV and advanced chronic kidney disease given the sustained virologic response across a broad spectrum of HCV genotypes. These results offer an effective treatment regimen for HCV infection in this high-risk, previously untreated or poorly treated population. For a patient like Mr. Smith, this regimen could be a viable option for treatment of his HCV infection.
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Lisa is a 2017-2018 NEJM Editorial Fellow. An otolaryngologist-head and neck surgeon by training, she graduated from the University of Toronto Medical School and completed her residency training at the University of Ottawa. She has a Master's in Public Health from the Harvard T. H. Chan School of Public Health.