Chen-Hua Liu1, Mei-Hsuan Lee2, Jou-Wei Lin3, Chun-Jen Liu4, Tung-Hung Su5, Tai-Chung Tseng5, Pei-Jer Chen4, Ding-Shinn Chen6, Jia-Horng Kao7. 1. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Douliou, Taiwan. 2. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. 3. Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Douliou, Taiwan. 4. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. 5. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan. 6. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan. 7. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: kaojh@ntu.edu.tw.
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.
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.
Authors: Mark Sulkowski; Laura E Telep; Massimo Colombo; Francois Durand; K Rajender Reddy; Eric Lawitz; Marc Bourlière; Nelson Cheinquer; Stacey Scherbakovsky; Liyun Ni; Lindsey Force; Heribert Ramroth; Anuj Gaggar; Anand P Chokkalingam; Meghan E Sise Journal: Aliment Pharmacol Ther Date: 2022-03-02 Impact factor: 9.524