The guidance for nephrologists regarding managing Hepatitis C in the CKD (dialysis and non-dialysis) comes from KDIGO, which suggested use of interferon or pegylated interferon with or without ribavarin (based on degree of kidney dysfunction). These therapies are associated with treatment-limiting toxic effects (they can cause or aggravate fatal or life-threatening autoimmune disorders, neuropsychiatric and ischemic disorders, and hemolytic anemia) as well as have sub-optimum efficacy. The most recent meta-analysis reported an overall estimate of sustained viral remission (SVR) in about one in three patients when treated for 16–48 weeks, whereas about 20–25% of patients did not complete the treatment due to adverse events. In addition, the longer treatment durations has meant patients being taken off the transplant waiting list while on therapy, adding to the dilemma about whether or not to treat. Notably, the use of interferon post kidney transplant is not recommended due to the increased risk of rejection.
This all changed with the introduction of direct acting antiretroviral (DAA) agents. This has opened a new paradigm in the management of Hepatitis C in the general population with SVR rates >90%, few adverse effects with the duration of therapy being as short as 8–12 weeks. However, the renal elimination (>80%) of sofosbuvir (which has been the most common drug used in the general population clinical trials) means this drug has to be used with caution in patients with kidney dysfunction (especially with one trial showing increased adverse events). Additionally, one of the trials which used sofosbuvir in a reduced dose in CKD population showed reduction in efficacy with SVR rates of only 40%.
This brings us to the C-Surfer Study. The C-Surfer Study, a randomized, parallel-group, multicenter, placebo-controlled Phase II/III trial, evaluated theefficacy and safety of grazoprevir and elbasvir (GZR/EBR) in HCV genotype 1–infected patients with Stage 4 or 5 CKD including patients on dialysis (N = 224). Patients were randomized to receive either immediate or deferred treatment with GZR/EBR (100/50 mg) once daily for 12 weeks. Patients randomized to the deferred treatment arm first received 12 weeks of placebo before starting GZR/EBR.
- The majority of patients were treatment naïve (80%)
- 6% were cirrhotic
- 81% had Stage 5 CKD
- 76% were on dialysis.
- SVR12 in all subjects (now including both the immediate and deferred treatment arms) who received GZR/EBR was 94.6 %
- immediate treatment group 94.3% [115/122]
- Deferred treatment group after placebo95% [96/101]).
- Only 12 subjects failed to attain SVR12
- virologic relapse was seen in 3 patients
- 1 patient stopping the regime for adverse events.
Post by Praveen Malavade, Nephrology Fellow, University of Ottawa