Evolution of renal function under direct-acting antivirals treatment for chronic hepatitis C: A real-world experience
Ming-Chao Tsai
Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taiwan
Search for more papers by this authorChun-Yen Lin
Division of Hepato-Gastroenterology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
Search for more papers by this authorChao-Hung Hung
Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Division of Hepato-Gastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
Search for more papers by this authorSheng-Nan Lu
Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Division of Hepato-Gastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
Search for more papers by this authorShui-Yi Tung
Division of Hepato-Gastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
Search for more papers by this authorRong-Nan Chien
Division of Hepato-Gastroenterology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
Search for more papers by this authorChih-Lang Lin
Division of Hepato-Gastroenterology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
Search for more papers by this authorJing-Houng Wang
Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Search for more papers by this authorChen Chien-Hung
Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Search for more papers by this authorKuo-Chin Chang
Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Search for more papers by this authorCorresponding Author
Tsung-Hui Hu
Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Correspondence
Tsung-Hui Hu, Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Kaohsiung, Taiwan.
Email: [email protected]
I-Shyan Sheen, Division of Hepato-Gastroenterology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.
Email: [email protected]
Search for more papers by this authorCorresponding Author
I-Shyan Sheen
Division of Hepato-Gastroenterology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
Correspondence
Tsung-Hui Hu, Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Kaohsiung, Taiwan.
Email: [email protected]
I-Shyan Sheen, Division of Hepato-Gastroenterology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.
Email: [email protected]
Search for more papers by this authorMing-Chao Tsai
Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taiwan
Search for more papers by this authorChun-Yen Lin
Division of Hepato-Gastroenterology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
Search for more papers by this authorChao-Hung Hung
Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Division of Hepato-Gastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
Search for more papers by this authorSheng-Nan Lu
Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Division of Hepato-Gastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
Search for more papers by this authorShui-Yi Tung
Division of Hepato-Gastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
Search for more papers by this authorRong-Nan Chien
Division of Hepato-Gastroenterology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
Search for more papers by this authorChih-Lang Lin
Division of Hepato-Gastroenterology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
Search for more papers by this authorJing-Houng Wang
Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Search for more papers by this authorChen Chien-Hung
Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Search for more papers by this authorKuo-Chin Chang
Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Search for more papers by this authorCorresponding Author
Tsung-Hui Hu
Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Correspondence
Tsung-Hui Hu, Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Kaohsiung, Taiwan.
Email: [email protected]
I-Shyan Sheen, Division of Hepato-Gastroenterology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.
Email: [email protected]
Search for more papers by this authorCorresponding Author
I-Shyan Sheen
Division of Hepato-Gastroenterology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
Correspondence
Tsung-Hui Hu, Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Kaohsiung, Taiwan.
Email: [email protected]
I-Shyan Sheen, Division of Hepato-Gastroenterology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.
Email: [email protected]
Search for more papers by this authorAbstract
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.
CONFLICTS OF INTEREST
All authors declare no relevant conflicts of interest.
REFERENCES
- 1Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis. 2005; 5(9): 558-567.
- 2Foster GR, Afdhal N, Roberts SK, et al. Sofosbuvir and velpatasvir for HCV genotype 2 and 3 infection. N Engl J Med. 2015; 373(27): 2608-2617.
- 3Kowdley KV, Gordon SC, Reddy KR, et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014; 370(20): 1879-1888.
- 4Nelson DR, Cooper JN, Lalezari JP, et al. All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study. Hepatology. 2015; 61(4): 1127-1135.
- 5Wornle M, Schmid H, Banas B, et al. Novel role of toll-like receptor 3 in hepatitis C-associated glomerulonephritis. Am J Pathol. 2006; 168(2): 370-385.
- 6Fabrizi F, Plaisier E, Saadoun D, Martin P, Messa P, Cacoub P. Hepatitis C virus infection, mixed cryoglobulinemia, and kidney disease. Am J Kidney Dis. 2013; 61(4): 623-637.
- 7Kwo PY, Badshah MB. New hepatitis C virus therapies: drug classes and metabolism, drug interactions relevant in the transplant settings, drug options in decompensated cirrhosis, and drug options in end-stage renal disease. Curr Opin Organ Transplant. 2015; 20(3): 235-241.
- 8Gutierrez JA, Lawitz EJ, Poordad F. Interferon-free, direct-acting antiviral therapy for chronic hepatitis C. J Viral Hepat. 2015; 22(11): 861-870.
- 9Pockros PJ, Reddy KR, Mantry PS, et al. Efficacy of direct-acting antiviral combination for patients with hepatitis C virus genotype 1 infection and severe renal impairment or end-stage renal disease. Gastroenterology. 2016; 150(7): 1590-1598.
- 10Roth D, Nelson DR, Bruchfeld A, et al. Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4–5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet. 2015; 386(10003): 1537-1545.
- 11Levey AS, Coresh J, Greene T, et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006; 145(4): 247-254.
- 12Xie D, Joffe MM, Brunelli SM, et al. A comparison of change in measured and estimated glomerular filtration rate in patients with nondiabetic kidney disease. Clin J Am Soc Nephrol. 2008; 3(5): 1332-1338.
- 13Stevens PE, Levin A; Kidney disease: improving global outcomes chronic kidney disease guideline development Work Group Members. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013; 158(11): 825-830.
- 14Summary of recommendation statements. Kidney Int Suppl (2011). 2013; 3(1): 5-14.
- 15Han WK, Wagener G, Zhu Y, Wang S, Lee HT. Urinary biomarkers in the early detection of acute kidney injury after cardiac surgery. Clin J Am Soc Nephrol. 2009; 4(5): 873-882.
- 16Haase M, Bellomo R, Devarajan P, et al. Novel biomarkers early predict the severity of acute kidney injury after cardiac surgery in adults. Ann Thorac Surg. 2009; 88(1): 124-130.
- 17Hsu YC, Lin JT, Ho HJ, et al. Antiviral treatment for hepatitis C virus infection is associated with improved renal and cardiovascular outcomes in diabetic patients. Hepatology. 2014; 59(4): 1293-1302.
- 18Hsu YC, Ho HJ, Huang YT, et al. Association between antiviral treatment and extrahepatic outcomes in patients with hepatitis C virus infection. Gut. 2015; 64(3): 495-503.
- 19Chen YC, Hwang SJ, Li CY, Wu CP, Lin LC. A Taiwanese nationwide cohort study shows interferon-based therapy for chronic hepatitis C reduces the risk of chronic kidney disease. Medicine (Baltimore). 2015; 94(32):e1334.
- 20Feng B, Eknoyan G, Guo ZS, et al. Effect of interferon-alpha-based antiviral therapy on hepatitis C virus-associated glomerulonephritis: a meta-analysis. Nephrol Dial Transplant. 2012; 27(2): 640-646.
- 21Park H, Chen C, Wang W, Henry L, Cook RL, Nelson DR. Chronic hepatitis C virus (HCV) increases the risk of chronic kidney disease (CKD) while effective HCV treatment decreases the incidence of CKD. Hepatology. 2018; 67(2): 492-504.
- 22Butt AA, Ren Y, Marks K, Shaikh OS, Sherman KE; ERCHIVES study. Do directly acting antiviral agents for HCV increase the risk of hepatic decompensation and decline in renal function? Results from ERCHIVES. Aliment Pharmacol Ther. 2017; 45(1): 150-159.
- 23Alvarez-Ossorio MJ, Sarmento E, Granados R, et al. Impact of interferon-free regimens on the glomerular filtration rate during treatment of chronic hepatitis C in a real-life cohort. J Viral Hepat. 2018.
- 24Saxena V, Koraishy FM, Sise ME, et al. Safety and efficacy of sofosbuvir-containing regimens in hepatitis C-infected patients with impaired renal function. Liver Int. 2016; 36(6): 807-816.
- 25Stevens LA, Coresh J, Greene T, Levey AS. Assessing kidney function–measured and estimated glomerular filtration rate. N Engl J Med. 2006; 354(23): 2473-2483.
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