Evolution of Renal Function Under Direct-acting Antivirals Treatment for Chronic Hepatitis C

A Real-world Experience

Ming-Chao Tsai; Chun-Yen Lin; Chao-Hung Hung; Sheng-Nan Lu; Shui-Yi Tung; Rong-Nan Chien; Chih-Lang Lin; Jing-Houng Wang; Chen Chien-Hung; Kuo-Chin Chang; Tsung-Hui Hu; I-Shyan Sheen

Disclosures

J Viral Hepat. 2019;26(12):1404-1412. 

In This Article

Abstract and Introduction

Abstract

Renal toxicity of direct-acting antivirals (DAAs) in chronic hepatitis C (CHC) patients has not been well-characterized. The aim of this study was to assess renal safety of DAAs in an Asian CHC patient cohort. Data from CHC patients (n = 1536) treated with DAAs were used in this retrospective study. Serial estimated glomerular filtration rate (eGFR) at pretreatment (1-year prior to treatment), baseline, end of treatment (EOT), and 12 weeks after treatment (SVR12) was evaluated. While a significant decrease in eGFR from baseline to EOT (84.8 → 81.8 mL/min/1.73 m2, P < .001) was observed; subsequently, a slight rise at SVR12 (84.3 mL/min/1.73 m2) was also evident. Changes in eGFR after DAA treatment were similar to those seen in PrOD, DCV/ASV and GZP/EBV regimens, except in the SOF-based regimen wherein eGFR remained unchanged from EOT to SVR12, especially in liver transplant recipients. Multivariate analysis revealed that age >65 years (OR = 1.862, P = .011), baseline eGFR ≥ 60 mL/min/1.73 m2 (OR = 2.684, P = .023), and liver transplant (OR = 3.894, P = .001) were independent risk factors for deteriorating renal function. In conclusion, DAA treatment led to a significant decline in eGFR at EOT but was followed by a slight rise at 12 weeks after treatment. A similar trend was observed with PrOD, DCV/ASV and GZP/EBV, but not in SOF-based regimens. As age >65 years, baseline eGFR ≥ 60 mL/min/1.73 m2 and liver transplantation are significant risk factors for deterioration in renal function, we strongly advice close monitoring of renal function in these populations.

Introduction

Chronic hepatitis C virus (HCV) infection is a major healthcare problem that affects approximately 130–170 million people worldwide.[1] Treatment with antiviral drugs vastly reduces both morbidity and mortality and improves health-related quality of life in HCV patients. Over the past few years, treatment options for chronic HCV infection have evolved dramatically and the new direct-acting antiviral (DAA) treatments offer an unprecedented opportunity to cure HCV infection. In clinical trials, DAAs have been shown to eliminate and cure HCV in >95% of patients with shorter treatment durations and with minimal adverse events not only in naïve patients, but also in patients who had previously failed to respond or could not be treated with interferon.[2–4]

HCV mainly targets the liver and leads to cirrhosis, hepatocellular carcinoma and death. Additionally, it also targets the kidney via either an immune cascade or cytopathic effect.[5,6] Metabolism and excretion occur in the kidney and the liver. As such impaired function of these organs may result in altered drug concentration leading to toxicity and/or subtherapeutic drug levels. Theoretically, sofosbuvir is the only DAA that has significant renal elimination, as the other currently approved DAAs–simeprevir, ledipasvir, paritaprevir/ritonavir, ombitasvir, dasabuvir, daclatasvir, asunaprevir, grazoprevir and elbasvir–are not eliminated by the kidneys, and thus, do not need dose adjustment, even in chronic kidney disease (CKD) or haemodialysis patients.[7] Although DAAs have fewer side effects compared to pegylated interferon plus ribavirin therapy,[8] few studies have documented the renal safety of DAAs, especially in patients with CKD. To date, only 2 RCTs in patients with severe CKD have shown high SVR rates;[9,10] however, little data are available on the renal toxicity exerted by DAAs for use in standard clinical practice. Therefore, we aimed to evaluate changes in estimated glomerular filtration rate (eGFR) due to the currently recommended all-oral therapy against HCV infection in Taiwan under real-world conditions.

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