Introduction to hepatitis C virus infection in patients with kidney disease: A roadmap for nephrologists

Abstract

In the nearly three decades that have followed the discovery of hepatitis C virus (HCV), numerous studies have described the far‐ reaching impact of this global health issue. It was not long after the identification of HCV as the cause of what was previously referred to as non‐A, non‐B hepatitis that it was shown to have a significantly higher prevalence in ESRD patients than the general population. Furthermore, HCV was unequivocally demonstrated to be both a cause and consequence of kidney disease. An extensive literature is now available that describes in detail the impact of HCV infection in patients with CKD, ESRD, and postkidney transplantation. Unfortunately, there were no well‐tolerated and effective treatment options for HCV‐infected patients with kidney disease during the interferon era. However, the availability of direct‐acting antiviral (DAA) agents that deliver cure rates routinely exceeding 90% in patients with CKD/ESRD and posttransplantation accompanied by excellent safety profiles has now focused the decision process onto which patients should receive treatment and what is the optimal time to initiate therapy. In this context, the current issue of Seminars in Dialysis is both timely and comprehensive and offers the reader a complete overview of HCV infection in patients with kidney disease. In the first article of this special edition, Fabrizi and colleagues provide a global perspective of the epidemiology of HCV infection in patients with advanced stage CKD/ESRD. They highlight that HCV hemodialysis prevalence rates have declined in Western Europe since the 1990s in concert with effective screening of blood products and implementation of universal precautions. However, HCV infection remains prevalent across the globe in the dialysis population and outbreaks continue to occur within dialysis facilities. The next contribution, by Cacoub and Comarmond, describes the extensive extrahepatic manifestations of HCV infection. In addition to being a cause of immune‐complex forms of kidney disease, they summarize the data associating HCV infection with an increased incidence of adverse cardiovascular outcomes, diabetes mellitus, and non‐Hodgkins lymphoma. In their paper, Hanson and Sise review the evidence that links HCV infection as both a cause of kidney disease while also accelerating the progression of preexisting CKD of other etiologies. Cottone and Bhamidimarri follow with a paper that provides an excellent guide to the assessment of chronic HCV infection in patients with advanced CKD. Besides providing very helpful information regarding interpretation of biochemical, virological, and radiological studies in the CKD population, they focus on the emergence of noninvasive testing as an alternative to liver biopsy in HCV‐infected patients. Nguyen, et al summarize the available data relevant to the important issue of transmission of disease within dialysis clinics. They point out that this continues to be an ongoing public health issue and is often the consequence of a breakdown in universal precautions. In the next paper in this issue, Bruchfeld and Lindahl elegantly discuss the clinical trials that have examined DAA therapy in patients with advanced CKD. Their review encompasses both randomized trials and real‐world experience and underscores the excellent efficacy and safety profiles of several of the DAA therapies in patients with impaired kidney function. This segues into the next article, by Cohen and Liapakis, who provide detailed insight into the pharmacokinetics of the DAA therapies, as well as important drug‐drug interactions to be cognizant of when treating patients with abnormal kidney function, including those on dialysis and/or on chronic transplant immunosuppression. Pagan and Roth extensively review the data on DAA treatment in ESRD patients. They give particular attention to the timing and choice of DAA therapy in patients on dialysis and how this might impact outcomes. Sawinski provides an overview of the important issue of HCV/ HIV co‐infection and how this has an adverse impact on patient outcomes. In their review, Wong and Bloom summarize the important information relating to HCV infection in the kidney transplant candidate and recipient. This is of particular importance as it relates to the timing of therapy and when it might be in the patient s best interest to delay DAA treatment until after transplantation. The very timely topic of transplanting kidneys from HCV‐infected donors into uninfected recipients is reviewed in the paper from Goldberg and Reese. An unfortunate consequence of the ongoing opioid epidemic in the United States is that many kidneys have become available from HCV‐infected donors. It is incumbent on the transplant community to determine how best to utilize these organs in a way that is safe for the patient and allows us to decrease the discard rate of these organs. In the concluding manuscript of this issue, Gordon, et al. succinctly summarize the 2018 Kidney Disease Improving Global Outcomes (KDIGO) Guidelines of Hepatitis C virus infection in patients with chronic kidney disease. In summary, although traditionally thought of predominantly in the context of liver disease, it is abundantly clear that HCV affects multiple systems and kidneys are not spared. Advancement in understanding the epidemiology of HCV, coupled with increasingly sensitive diagnostic testing has helped to shed light on the fact that HCV infection is an important cause of morbidity and mortality across the entire spectrum of patients with kidney disease, especially those DOI: 10.1111/sdi.12775