Evolution of eGFR in chronic HCV patients receiving sofosbuvir-based or sofosbuvir-free direct-acting antivirals
Journal
Journal of Hepatology
Journal Volume
72
Journal Issue
5
Pages
839-846
Date Issued
2020
Author(s)
Abstract
Background & Aims: Data regarding the nephrotoxicity of sofosbuvir (SOF) remain controversial. We compared the evolution of estimated glomerular filtration rate (eGFR) in patients with chronic HCV infection receiving SOF-based or SOF-free direct-acting antivirals (DAAs). Methods: A total of 481 patients with compensated liver diseases and eGFR ?30 ml/min/1.73m2, receiving SOF-based (n = 308) or SOF-free (n = 173) DAAs for 12 weeks, were prospectively enrolled. The eGFR was assessed from baseline to off-treatment week 24 using the chronic kidney disease (CKD)-epidemiology collaboration equation. Differences in the evolution of eGFR between regimens were compared by a generalized linear mixed-effects model. Multivariate analysis was performed for factors affecting eGFR evolution. Results: Patients receiving SOF-based DAAs experienced a significant on-treatment decline in eGFR (adjusted slope coefficient difference: ?1.24 ml/min/1.73m2/month; 95% CI ?1.35 to ?1.13; p <0.001) and a significant off-treatment improvement (adjusted slope coefficient difference: 0.14 ml/min/1.73m2/month; 95% CI 0.08 to 0.21; p = 0.004) compared to patients receiving SOF-free DAAs. Multivariate analysis showed age per 1-year increase (adjusted slope coefficient difference: ?0.05 ml/min/1.73m2/month; 95% CI ?0.05 to ?0.04; p <0.001), SOF-based DAAs (adjusted slope coefficient difference: ?0.33 ml/min/1.73m2/month; 95% CI ?0.49 to ?0.17; p <0.001), and CKD stage (adjusted slope coefficient difference: ?1.44 ml/min/1.73m2/month; 95% CI ?1.58 to ?1.30; p <0.001 for stage 3 vs. 1, and ?3.59 ml/min/1.73m2/month; 95% CI ?3.88 to ?3.30; p <0.001 for stage 2 vs. 1) were independent factors affecting eGFR evolution from baseline to off-treatment week 24. Conclusions: Patients receiving SOF-based DAAs exhibited a quadratic trend, with eGFR worsening on treatment and improving off treatment. Increasing age, SOF-based DAAs, and more advanced baseline CKD stage are independently associated with a decline in eGFR in patients with HCV receiving DAAs. Lay summary: While the efficacy of sofosbuvir for the treatment of hepatitis C virus is clear, data regarding its possible nephrotoxicity are controversial. Herein, we showed that sofosbuvir worsened on-treatment kidney function but led to an off-treatment improvement. Our findings suggest that treating physicians should be alert to risk factors for kidney dysfunction before initiating direct-acting antiviral treatment for patients with hepatitis C virus infection. Clinical trial number: NCT04047680 ? 2019 European Association for the Study of the Liver
SDGs
Other Subjects
alanine aminotransferase; antivirus agent; aspartate aminotransferase; bilirubin; creatinine; ribavirin; serum albumin; sofosbuvir; antivirus agent; hepatitis C antibody; ribavirin; sofosbuvir; virus RNA; adult; Article; chronic hepatitis C; clinical assessment; comparative study; controlled study; disease association; epidemiological data; estimated glomerular filtration rate; female; human; kidney function; liver disease; major clinical study; male; middle aged; nephrotoxicity; priority journal; prospective study; treatment indication; aged; blood; chronic hepatitis C; combination drug therapy; drug effect; genetics; genotype; glomerulus filtration rate; Hepacivirus; immunology; kidney failure; procedures; sustained virologic response; virology; Adult; Aged; Antiviral Agents; Drug Therapy, Combination; Female; Genotype; Glomerular Filtration Rate; Hepacivirus; Hepatitis C Antibodies; Hepatitis C, Chronic; Humans; Male; Middle Aged; Prospective Studies; Renal Insufficiency; Ribavirin; RNA, Viral; Sofosbuvir; Sustained Virologic Response
Publisher
Elsevier B.V.
Type
journal article