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New treatment for hepatitis C in chronic kidney disease, dialysis, and transplant
Fabrizio Fabrizi1, Paul Martin2, Piergiorgio Messa3
1Division of Nephrology and Dialysis, Maggiore Hospital and IRCCS Foundation, Milano, Italy; Division of Hepatology, School of Medicine, University of Miami, Miami, Florida, USA.
Insights
Direct-acting antivirals offer high efficacy for treating hepatitis C virus (HCV) in chronic kidney disease patients, improving survival. Further research is needed on safety and cost-effectiveness for widespread use.
Area of Science:
- Nephrology
- Hepatology
- Infectious Diseases
Background:
- Chronic hepatitis C (HCV) negatively impacts survival in dialysis and transplant patients.
- HCV infection is linked to an increased risk of developing chronic kidney disease (CKD).
- Previous interferon treatments showed limited efficacy and safety in CKD patients.
Purpose of the Study:
- To review the efficacy and safety of direct-acting antivirals (DAAs) for treating HCV in patients with CKD.
- To highlight the potential of DAAs in eradicating HCV in kidney disease populations.
- To address the knowledge gaps regarding DAA treatment in CKD patients.
Main Methods:
- Review of published data and ongoing clinical trials on DAAs for HCV in CKD patients.
- Analysis of efficacy (sustained virologic response rates) and safety profiles of DAA regimens.
- Consideration of specific DAA combinations like grazoprevir/elbasvir and sofosbuvir/simeprevir.
Main Results:
- Grazoprevir/elbasvir demonstrated excellent efficacy (94.3% SVR) and safety in CKD stages 4-5 with HCV genotype 1.
- Sofosbuvir/simeprevir showed an 89% viral response in a small cohort of end-stage renal disease patients.
- Ongoing trials are evaluating other DAA combinations, including sofosbuvir-based regimens.
Conclusions:
- Direct-acting antivirals represent a promising strategy for HCV eradication in kidney disease patients.
- Cost and potential adverse drug reactions with comorbidities remain significant considerations for DAA use in CKD.
- Further research is crucial to optimize DAA treatment protocols for this vulnerable population.
Abstract:
The evidence that chronic hepatitis C plays a detrimental role in survival among patients on maintenance dialysis or renal transplant recipients promotes the antiviral treatment of hepatitis C virus (HCV) among chronic kidney disease patients. Also, it seems that HCV infection is associated with an increased risk of developing chronic kidney disease in the adult general population. Interferon-based regimens have provided limited efficacy and safety among chronic kidney disease patients, whereas the advent of the new direct-acting antivirals for the treatment of hepatitis C (launched over the past 5 years) has given the opportunity to reach sustained virologic response rates of 90% for many patient groups. Unfortunately, poor information exists regarding the antiviral treatment of hepatitis C in the chronic kidney disease population. The first published data on the treatment of hepatitis C among patients with chronic kidney disease (stage 4-5) and HCV genotype 1 regard the grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor) combination; excellent efficacy (sustained viral response, 94.3%; 115/122) and safety have been achieved. Preliminary evidence on the combined treatment of sofosbuvir (NS5B inhibitor) and simeprevir (NS3/4A inhibitor) has given a viral response of 89%, but the size of the study group (n = 38 patients with end-stage renal disease) was small. Some phase 2 and 3 clinical trials based on other antiviral combinations (3D regimen, sofosbuvir/ledipasvir, or other sofosbuvir-containing approaches) are ongoing. Thus, the antiviral regimens based on direct-acting antivirals promise to play a pivotal role in the eradication of hepatitis C among kidney disease patients. Direct-acting antivirals are very expensive; in an era of cost containment this is a crucial point either in developed and developing countries. Adverse drug reactions resulting from concomitantly administered medications are another ongoing concern for patients undergoing HCV treatment, particularly for chronic kidney disease patients who have a heavy burden of comorbidities.
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