Effect of Renal Dysfunction on DAA Regimens With Ribavirin in HCV

Patients with chronic hepatitis C virus (HCV) and renal dysfunction may be a difficult-to-treat population when considering ribavirin combination regimens, even in the era of interferon-free direct acting antiviral (DAA) therapy, according to retrospective study results published in Hepatology Research.¹

IFN-free DAA regimens demonstrate high safety and tolerability, even in patients with renal impairment,^2-7 but it is unclear how renal impairment affects these treatment regimens. Therefore, researchers in Japan investigated the effect of renal impairment on the tolerability and virologic efficacy of IFN-free ribavirin-DAA regimens in 189 patients with chronic HCV infection by comparing the incidence of ribavirin-induced anemia, ribavirin dose reduction, and virologic efficacy to baseline renal function as defined by the estimated glomerular filtration rate (eGFR).¹ 

Treatments included a 12-week regimen of sofosbuvir (400 mg) once daily and ribavirin, and a 16-week regimen of ombitasvir, paritaprevir, and ritonavir (25/150/100 mg, respectively) once daily and ribavirin. In both regimens, the dose of ribavirin was adjusted based on patient body weight and was administered twice daily. The researchers found that patients with renal dysfunction (eGFR=30-59 mL/min/1.73 m2) had a higher rate of ribavirin dose reduction and more marked decreases in ribavirin levels. The sustained virologic response rate was significantly lower in patients who required a ribavirin dose reduction than in patients who did not (P <.0001). However, there were no statistically significant differences in sustained virologic response rates according to renal function overall.

The study authors concluded that, “Baseline renal dysfunction may unfavorably affect the outcomes of [ribavirin]-DAA in patients with chronic HCV infection due to the increased risk of RBV dose reduction, even in the era of IFN-free DAA regimens.”¹

References

1. Nakashima M, Toyoda H, Tada T, et al. Influence of renal dysfunction on dose reduction and virological efficacy of regimens combining ribavirin and all–oral direct acting antivirals in patients with chronic hepatitis C virus infection [published online January 10, 2019]. Hepatol Res. doi:10.1111/hepr.13311
2. Toyoda H, Kumada T, Tada T, et al. Efficacy and tolerability of an IFN-free regimen with DCV/ASV for elderly patients infected with HCV genotype 1B. J Hepatol. 2017;66:521-527.
3. Ogawa E, Furusyo N, Yamashita N, et al. Effectiveness and safety of daclatasvir plus asunaprevir for patients with hepatitis C virus genotype 1b aged 75 years and over with or without cirrhosis. Hepatol Res. 2017;47(3):E120-E131.
4. Akuta N, Sezaki H, Suzuki F, et al. Favorable efficacy of daclatasvir plus asunaprevir in treatment of elderly Japanese patients infected with HCV genotype 1b aged 70 and older. J Med Virol. 2017;89:91-98.
5. Ishigami M, Hayashi K, Honda T, et al. Daclatasvir and asunaprevir treatment in patients with severe liver fibrosis by hepatitis C virus genotype 1b infection: real-world data. J Gastroenterol Hepatol. 2017;32:1879-1886.
6. Suda G, Nagasaka A, Yamamoto Y, et al. Safety and efficacy of daclatasvir and asunaprevir in hepatitis C virus infected patients with renal impairment. Hepatol Res. 2017;47:1127-1136.
7. Arai T, Atsukawa M, Tsubota A, et al. Efficacy and safety of ombitasvir/paritaprevir/ritonavir therapy for genotype 1b chronic hepatitis C patients complicated with chronic kidney disease. Hepatol Res. 2018;48:549-555.