The 2008 KDIGO guideline on the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD) was the very first guideline produced by KDIGO. Since then, there have been dramatic changes in the field of antiviral treatments, which prompted a timely reassessment and publication of this guideline update in 2018 (1). The purpose of this short review is to summarize the key recommendations from this important guidance document.
As in the previous guideline edition, Chapter 1 addresses the detection and evaluation of HCV in CKD. It should be stressed that the guideline now recommends that all patients be screened once for HCV at the time of initial CKD evaluation. This new recommendation is based on multiple large observational studies that have consistently identified HCV positivity as a risk factor for adverse clinical outcomes, independently of classic CKD and cardiovascular risk factors. These adverse outcomes include CKD onset, rapid CKD progression, and development of ESKD and cardiovascular complications.
Recent evidence further shows that in patients with various causes of CKD, including diabetic nephropathy or nephrosclerosis, and thus not just HCV-associated membranoproliferative glomerulonephritis, HCV treatment is associated with delayed onset of CKD (2) and cardiovascular complications. The cost of a single immunoassay for HCV thus appears small in comparison with the potential clinical benefit(s). A second key change in this chapter is the recommendation to start investigating HCV-positive patients via non-invasive means such as transient elastography (e.g., FibroScan) and/or biochemical indexes. These have indeed been shown, even in late CKD patients including candidates for kidney transplantation, to accurately quantify noninvasively the extent of liver fibrosis. Thus, a liver biopsy is now required only if there is a high suspicion of another cause of liver disease than HCV, and/or if noninvasive results are discordant (1).
Chapter 2 addresses HCV antiviral treatments, also known as direct-acting antiviral agents (DAAs), which can effectively cure HCV infections in more than 95% of cases over a course of 12 weeks. DAA treatments thus now become the rule rather than the exception in CKD patients as well, if life expectancy is reasonable (no uniform minimum threshold can be proposed, although a life expectancy of at least 12 months appears reasonable). As highlighted in Figure 1, certain DAA regimens can be used even in patients with an eGFR <30 mL/min per 1.73 m2. Similarly, prevalent kidney transplant recipients can also be treated effectively and safely with DAA regimens (Figure 2), with careful attention to the level of immunosuppressive agents during DAA treatment so as to minimize the risk of drug–drug interactions.
Chapter 3 deals with the prevention of nosocomial HCV transmission within hemodialysis units. This risk remains significant, as shown by a very recent Dialysis Outcomes and Practice Patterns Study report (3). Thus, the guideline still recommends meticulous attention to hygienic precautions and regular auditing of infection control procedures. Also, in line with the 2008 KDIGO guideline and the recommendations by the United States Centers for Disease Control and Prevention, the guideline still does not advocate the use of dedicated dialysis machines for HCV-positive patients or the isolation of HCV-positive patients in a specific ward. These are indeed unnecessary and may tend to reduce the attention devoted to proper infection control practices.
Chapter 4 addresses the management of HCV before and after kidney transplantation. The key point here is that as a result of the ongoing opioid epidemic, there is currently a significant number of HCV-positive organs available for transplantation, whose acceptance by HCV positive recipients may markedly shorten their waiting time for a graft. This calls for a collaboration with transplantation centers in decisions about the timing of HCV treatment in potential candidates for a kidney transplant.
The decision to treat HCV before versus after kidney transplantation will therefore be dependent on the severity of liver disease (which may prompt a simultaneous kidney-liver transplantation in cases of decompensated cirrhosis) but will also be markedly influenced by the expected waiting time for a kidney graft, as detailed in Figure 3. Interestingly, recent evidence shows that HCV-negative recipients who are willing to accept HCV-positive organs may also undergo transplantation much more rapidly than otherwise and have good outcomes. However, given the unknown long-term safety of this approach, the KDIGO Work Group thought that this practice should remain strictly investigational pending further studies.
Chapter 5 discusses the management and treatment of HCV-associated glomerulonephritis. In patients with rapidly progressive glomerulonephritis, severe cryoglobulinemia or nephrotic syndrome, the guideline now recommends immunosuppressive treatment with rituximab in addition to DAA treatment. This recommendation is based on two randomized controlled trials, admittedly relatively small, demonstrating the efficacy and superiority of rituximab over alternative regimens (5).
Over the past decade, remarkable progress has been achieved in the management of HCV. The shift from weaker guideline statements a decade ago to the present strong recommendations on HCV treatment can be attributed to the arrival of these highly effective and well-tolerated DAA regimens. As such, this is the right time for nephrologists to greatly reduce the burden of HCV in CKD patients in line with the World Health Organization’s commitment to eliminate viral hepatitis as a significant public health problem by 2030 (6).
KDIGO 2018 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int Suppl 2018; 8:91–165.
Park H, et al. Chronic hepatitis C virus (HCV) increases the risk of chronic kidney disease (CKD) while effective HCV treatment decreases the incidence of CKD. Hepatology 2018; 67:492–504.
Jadoul M, et al. Prevalence, incidence, and risk factors for hepatitis C virus infection in hemodialysis patients. Kidney Int 2019; 95:939–947.
De Vita S, et al. A randomized controlled trial of rituximab for the treatment of severe cryoglobulinemic vasculitis. Arthritis Rheum 2012; 64:843–853.