Direct-acting antiviral therapy slows kidney function decline in patients with Hepatitis C virus infection and chronic kidney disease

Abstract

Hepatitis C virus (HCV) infection is common and can accelerate chronic kidney disease (CKD) progression. Direct-acting antiviral (DAA) therapies against hepatitis C have consistently shown rates of sustained viral remission. However, the effect on kidney function is unknown. In a retrospective observational cohort study of HCV-infected patients receiving DAA therapies from 2013 to 2017, the slopes of estimated glomerular filtration rate (eGFR) decline were compared in the three years before DAA therapy to the slope after therapy. Pre-and post-treatment albuminuria values were also compared. In all, 1,178 patients were included; mean age of 56, 64% male, 71% white, 21% were diabetic, and 42% with cirrhosis. In patients with eGFR less than 60ml/min per 1.73m 2 , the annual decline in eGFR in the three years prior to treatment was −5.98 ml/min per year (95% confidence interval −7.30 to −4.67) and improved to −1.32 ml/min per year (95% confidence interval −4.50 to 1.88) after DAA therapy. In patients with eGFR greater than 60ml/min per 1.73m 2 the annual decline in eGFR in the three years prior to treatment was −1.43 ml/min per year (95% confidence interval −1.78 to −1.08) and after DAA therapy was −2.32 ml/min per year (95% confidence interval −3.36 to −1.03). Albuminuria improved significantly in patients without diabetes, but not in those with diabetes. Predictors of eGFR improvement included having CKD at baseline and being non-diabetic. Events of acute kidney injury were rare, occurring in 29 patients, and unrelated to antiviral therapy in 76% of cases. Thus, DAA therapy for HCVs infection may slow CKD progression.

Low Complement C4 Predicts Improvement of Kidney Function After Direct‐Acting Antiviral Therapy for Hepatitis C Virus

“…We validated that low C4 status was associated with improvement in eGFR after DAA therapy in a large, real-world cohort of DAA-treated patients in our health care network. (12) Low serum level of complement C4 is a marker of immune complex disease; it is consumed by activation of complement by the classical pathway. This can be trigged by cryoglobulinemia, which may be high grade or low grade and may or may not be associated with other symptoms of mixed cryoglobulinemic syndrome.…”

“…The details of the overall cohort of DAA-treated patients have been previously published. (12) DAA therapy was prescribed at the discretion of the treating physician; treatment regimens depended on the genotype, presence of cirrhosis, and prior treatment experience. We obtained patient laboratory data from the Research Patient Data Registry at Partners Healthcare System.…”

“…(14) We compared the average eGFR before and after DAAs in all patients who had baseline complement C4 levels measured before initiating DAA therapy. (12) Low C4 was again defined as less than 12 mg/dL, per the reference range of our laboratory. Baseline characteristics of the cohort were described using mean ± SD, median and interquartile range (IQR), or percent.…”

“…We identified 125 patients with CKD who received DAAs during the study period. (12) Sixty patients with CKD had complement C4 level measured before beginning DAA therapy. Ten were excluded because they lacked follow-up serum creatinine Fig.…”

“…(7)(8)(9) We have recently shown that DAA therapy may improve kidney function (estimated glomerular filtration rate [eGFR] and proteinuria) in patients with CKD. (10)(11)(12) However, the mechanism by which DAAs improve kidney disease and proteinuria is unclear. The aim of this study was to characterize changes in kidney function during DAA therapy, and to determine whether any baseline characteristics could predict which patients had improvement in kidney function markers during DAA therapy.…”