HEPATITIS C VIRUS INFECTION IN PATIENTS WITH KIDNEY DISEASE: A ROADMAP FOR NEPHROLOGISTS Guest Editors: Roy D. Bloom and David Roth Treating hepatitis C virus in dialysis patients: How, when, and why? Javier Pagan 1 | Marco Ladino 1,2 | David Roth 1 1 Katz Family Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, Florida 2 Nephrology Section, Miami Veterans Administration Healthcare System, Miami, Florida Correspondence David Roth, Katz Family Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, FL. Email: d.roth@miami.edu Abstract The identification of hepatitis C virus (HCV) occurred in 1989, and soon thereafter, it was recognized that there was a higher prevalence of anti‐HCV seropositivity in patients with end‐stage renal disease (ESRD) when compared to the general popula- tion. Multiple extrahepatic manifestations have been associated with HCV infection in patients with ESRD; these include an increased prevalence and risk of cardiovas- cular complications, insulin resistance, diabetes mellitus, and lymphoproliferative dis- orders. Infection with HCV has also been associated with an increased relative risk of mortality in the ESRD patient when contrasted to those patients without infec- tion. The availability of second‐generation direct‐acting antiviral agents has revolu- tionized the treatment of HCV in both the general population as well as those patients with advanced chronic kidney disease and receiving dialysis. These new treatment protocols are very well tolerated with limited side effects and manageable drug‐drug interactions while achieving remarkable sustained viral response rates. It is important that nephrologists become familiar with the differing strategies available for HCV‐infected ESRD patients so that the appropriate decision of when and who to treat can be made for each patient. 1 | INTRODUCTION Estimates are that hepatitis C virus (HCV) infection affects approxi- mately 150‐170 million people globally. 1 The prevalence of HCV infection in patients with end‐stage renal disease (ESRD) has been demonstrated to exceed that of the general population and HCV infection has been associated with a higher morbidity and mortality because of both the hepatic and extrahepatic manifestations of the disease. 2 The virus exhibits a tropism for B‐lymphocytes, and as a consequence, the infection has been associated with an increased incidence of B‐cell non‐Hodgkin lymphoma, mixed cryoglobulinemia, immune complex deposition disease, and several autoimmune condi- tions. In addition, infected patients have a higher incidence of adverse cardiovascular events, type 2 diabetes mellitus, and insulin resistance. 1,3 As a result, infection with HCV is accompanied by worsened clinical outcomes in ESRD patients regardless of the dialy- sis modality being offered to the patient (Figure 1). 3,4 It has been estimated that HCV infection is present in approxi- mately 5%‐10% of the US dialysis population. 1 In a meta‐analysis of ESRD patients, HCV infection was associated with a relative risk of mortality of 1.34 (95% CI 1.25‐1.47), with both cirrhosis and hepato- cellular carcinoma being more frequent causes of death. 5 In a sepa- rate analysis, HCV‐infected ESRD patients demonstrated an increased risk for both liver and cardiovascular disease‐related mor- tality when compared to uninfected patients. 6 ESRD patients with chronic HCV infection and a viral load > 2 × 10 6 IU/mL have a higher prevalence of coronary artery calcium and arterial plaque for- mation with subclinical cardiovascular disease. 7 Accelerated athero- genesis in HCV‐infected patients has been attributed to activation of the systemic inflammatory response. 8 Data from the Dialysis Outcomes and Practice Patterns Study corroborated the increased mortality risk accompanying HCV infec- tion 9 while also demonstrating that disappointing few HCV‐positive DOI: 10.1111/sdi.12764 Seminars in Dialysis. 2018;1–7. wileyonlinelibrary.com/journal/sdi © 2018 Wiley Periodicals, Inc. | 1