Therapy with DAAs in patients with chronic hepatitis C and advanced chronic kidney disease: Real-world experience of the German Hepatitis C Registry

Background and aims:

Real-world experience with direct antiviral agents (DAA) in patients with chronic hepatitis C virus (HCV) infection and a glomerular filtration rate (GFR) < 30 ml/min is limited to case series so far. The German Hepatitis C-Registry (DHC-R) is a prospective, multicentre real-world registry study for patients with chronic hepatitis C. We investigated the safety and effectiveness of novel DAAs in patients with impaired kidney function.

Methods:

The DHC-R comprises approximately 11,000 patients recruited by more than 250 centres. Patients are treated at the discretion of the physician. The present analysis is based on 5,833 patients with treatment initiation between February 2014 and September 2015.

Results:

Overall, antiviral therapy was associated with a GFR improvement in 330/4,527 (7.3%) individuals, a deterioration to GFR < 30 ml/min occurred in in 9/4483 (0.2%) patients. Only 46/5,833 (0.8%) patients initiated antiviral therapy with a baseline GFR of < 30 ml/min (87%/9%/4% HCV-genotype 1/3/4; 26% cirrhosis; 54% treatment-naïve, 43% interferon-experienced). They suffered significantly more frequently from hypertension, coronary heart disease and chronic heart failure than individuals with GFR > 30 ml/min. Treatment regimens were based on sofosbuvir (ribavirin n = 2, simeprevir n = 3, daclatasvir n = 5, ledipasvir n = 18; each ± ribavirin) or paritaprevir/r, ombitasvir ± dasabuvir ± ribavirin (n = 18). Adverse events did not occur more often in patients with GFR < 30 vs. > 30 ml/min (treatment without ribavirin: 58% vs. 50%; treatment with ribavirin 67% vs. 72%), however, serious adverse events were significantly more frequently in individuals with GFR < 30 ml/min (treatment without ribavirin: 13% vs. 3%, p = 0.02; treatment with ribavirin 33% vs. 5%, p < 0.001). Treatment discontinuation due to (serious) adverse events occurred more often in patients with GFR < 30 ml/min (6.5% vs. 1.1%; p = 0.02) and were associated with the use of ribavirin. Overall sustained virologic response rates (SVR12) did not differ significantly between cases with GFR < 30 vs. > 30 ml/min (91% vs. 97%).

Conclusions:

Adherence to treatment guidelines were very high in this large real world cohort as only few patients started sofosbuvir-based therapy with a baseline GFR of < 30 ml/min. However, safety and efficacy was good in selected patients with impaired kidney function but RBV was a main cause of treatment discontinuations. RBV-free treatment options like grazoprevir/elbasvir or glecaprevir/pibrentasvir will therefore be of major importance for these patients.