In a systematic review performed to support the recent Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for the treatment of hepatitis C virus (HCV) in patients with kidney diseases (1), Balk and colleagues have summarized the safety and efficacy of direct-acting antivirals (DAAs) used to treat HCV in patients with chronic kidney disease (CKD). The authors analyzed all available studies in patients with pre-dialysis CKD (stage 4/5), patients with kidney failure receiving dialysis, and kidney transplant recipients (KTRs), focusing on a sustained virologic response at 12 weeks (SVR12) and clinically significant adverse events (those leading to hospitalization or treatment discontinuation) (1).
Overwhelmingly, DAAs were highly effective and had low adverse event rates across all three patient groups (Table 1). The authors found no direct evidence of clinically meaningful differences between DAA regimens; they also noted that current first-line treatment recommendations favored using pan-genotypic DAA regimens, including sofosbuvir and velpatasvir (EpclusaTM) or glecaprevir and pibrentasvir (MavyretTM). Importantly, knowledge of drug-drug interactions between DAAs and immunosuppressive agents is important for treating KTRs. Both sofosbuvir/velpatasvir and glecaprevir/pibrentasvir can be co-administered with tacrolimus, but levels need to be closely monitored, as both DAAs and improvements in liver function induced by DAAs can impact tacrolimus levels. Patients taking glecaprevir/pibrentasvir should not take >100 mg of cyclosporin per day due to drug-drug interactions. Patients taking sirolimus should have drug levels monitored if taking glecaprevir/pibrentasvir due to a drug-drug interactions; there is no interaction between sofosbuvir/velpatasvir and sirolimus. Finally, although no major safety concerns emerged in the kidney failure population, very few patients receiving peritoneal dialysis were studied (35 of the 3817 with kidney failure).
Summary of efficacy and safety of DAA usage by kidney disease group
The comparable safety of sofosbuvir-based therapies and their expanded approval in kidney failure increase the opportunity for DAA treatment in many lower- and middle-income countries, where sofosbuvir-based therapies may be the only accessible therapy (2), and in patients with advanced cirrhosis who cannot tolerate protease inhibitor-based therapy (glecaprevir).
HCV infection is associated with more rapid progression of CKD (3), and nephrologists should be aware that DAAs produce high cure rates and are well tolerated. Currently approved pan-genotypic regimens are approved for all levels of kidney function. This systematic review compellingly indicates that DAA treatment for patients with CKD, kidney failure, and KTRs is safe and effective. Referring patients with HCV for DAA therapy is an important part of optimizing their health and survival.
References
- 1. ↑
Martin P, et al. Executive summary of the KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int 2022; 102:1228–1237. doi: 10.1016/j.kint.2022.07.012
- 2. ↑
Ali S, et al. Improving access to the treatment of hepatitis C in low- and middle-income countries: Evaluation of a patient assistance programme. Int J Clin Pharm 2021; 43:958–968. doi: 10.1007/s11096-020-01202-1
- 3. ↑
Molnar MZ, et al. Association of hepatitis C viral infection with incidence and progression of chronic kidney disease in a large cohort of US veterans. Hepatology 2015; 61:1495–1502. doi: 10.1002/hep.276640
