A research group from Hokkaido University in Japan found that standard treatment for those with genotype 1 HCV should likely be switched from interferon (INF)-based therapies to INF-free direct-acting antiviral (DAA) therapies.
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According to the research team, infection with HCV can result in glomerulonephritis, and can even lead to end-stage renal disease. In addition, there is a high rate of HCV infection in patients who suffer from end-stage renal dysfunction, even in those who are receiving hemodialysis treatment. Even so, patients with HCV infection on hemodialysis, face a significantly worse prognosis than those who are not on the treatment. INF-based therapy has been the standard treatment for patients with severe renal dysfunction with HCV; however, the research team from Hokkaido University in Japan believe that increased rates of sustained viral response (SVR) are yet to be achieved through this standard therapy.
Trials of DAA-based therapies, which are INF-free, have shown significant improvements in SVR; however, one drawback, according to the authors, is that patients with severe renal dysfunction are largely excluded from such trials. Recent studies have shown that INF-free therapies are safe and efficient for patients with severe renal dysfunction. This review focused on both traditional and novel treatments for patients with both severe renal dysfunction and HCV infection.
Previous to the development of DAAs, the recommended HCV treatment for patients with renal dysfunction consisted of pegylated (PEG)-INF therapy. However, for those with severe renal dysfunction, hemodialysis cannot remove INF from the blood, due to its high molecular weight. The research group looked at studies that examined both PEG-INF monotherapy and INF combined with ribavirin (RBV). In both types of treatment, the kidneys were unable to eliminate the substances in patients with severe renal dysfunction, so they were determined unsatisfactorily safe or efficient.
The authors noted that for patients receiving hemodialysis as well as DAA therapy, clinicians must pay special attention to drug-drug interactions and exercise caution. They reviewed studies investigating the use of grazoprevir and elbasvir combination therapy, paritaprevir (PTV)/ritonavir, ombitasvir (OBV), and dasabuvir (DSV) with or without RBV, asunaprevir (ASV) and daclatasvir (DCV) combination therapy, and sofosbuvir-based therapy.
Adminsitration of grazoprevir and elbasvir combination therapy in patients with renal dysfunction is safe and effective, as is PTV/ritonavir/OBV with or without DSV, according to the report. The team described DCV/ASV as being “highly effective and safe for patients with severe renal dysfunction.” Sofosbuvir is effective and has a high genetic barrier; however, the research group stated that data regarding use of sofosbuvir in patients with severe renal dysfunction is still pending.
“If a good prognosis is expected, dialysis patients with genotype 1 HCV infection should be considered for DAAs therapy,” the team concluded, but added that in cases other than genotype 1 HCV, “waiting for the next generation DAAs would be the optimal treatment option.” Clinical trials for those next generation DAAs are currently underway.
