Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C Virus Infection in Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2018 Clinical Practice Guideline

Abstract

The first clinical practice guideline published by Kidney Disease: Improving Global Outcomes (KDIGO) was its 2008 guideline on the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD) (1, 2). In the subsequent 10 years, the development of direct-acting antivirals (DAAs), which enabled a greater than 95% rate of viral eradication in CKD populations infected with HCV, prompted KDIGO to update its 2008 guideline (3, 4). The guideline s overall objective is to inform the management of HCV infection, including the use of DAAs in adults with CKD. Its target audience includes nephrologists, transplant physicians, hepatologists, infectious disease specialists, primary care physicians, and other practitioners caring for adults with HCV infection and CKD worldwide. Like the original 2008 HCV and CKD guideline, recommendations are divided into 5 chapters addressing the detection and evaluation of HCV in CKD, treatment of HCV infection in patients with CKD, prevention of HCV transmission in hemodialysis units, management of HCV-infected patients before and after kidney transplantation, and diagnosis and management of kidney diseases associated with HCV infection. Within the guideline, recommendations for clinical practice, implementation, and future research are highlighted. The guideline seeks to provide comprehensive guidance encompassing all aspects of managing HCV infection in CKD populations (Appendix Figure) and considers implementation across international settings where HCV and CKD are encountered. The complete version is available at www.kdigo.org and includes 66 recommendations. This synopsis focuses on 32 key recommendations relevant to clinical practice regarding HCV infection in patients with CKD. The major topics of the remaining 34 recommendations include the prevention of HCV transmission in hemodialysis units, CKD testing in HCV-infected patients, performance characteristics of noninvasive tests of hepatic fibrosis, and decisions regarding liverkidney versus kidney-only transplantation. Appendix Figure. Prognosis of CKD, by categories of GFR and albuminuria. Chronic kidney disease is defined as abnormalities of kidney structure or function that are present for >3 months and have health implications. It is classified on the basis of cause, GFR category (G1 to G5), and albuminuria category (A1 to A3 [presented as albumincreatinine ratios]). Green means low risk (no CKD if no other markers of kidney disease), yellow means moderately increased risk, orange means high risk, and red means very high risk. The suffix D denotes dialysis (for example, CKD G5D refers to a patient with CKD stage G5 who is receiving dialysis). CKD = chronic kidney disease; GFR = glomerular filtration rate; KDIGO = Kidney Disease: Improving Global Outcomes. (Reproduced with permission of KDIGO.). Guideline Development Process, Evidence Grading, and Stakeholder Consultation The work group consisted of an international body of clinicians and researchers, including nephrologists, hepatologists, virologists, a representative from the Centers for Disease Control and Prevention (CDC), and a professional evidence review team. The work group formulated the scope of the guideline and graded evidence on the basis of the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system (5) in accordance with KDIGO s usual practice (Appendix Tables 1 and 2). Appendix Table 1. GRADE Criteria Used for Grading the Strength of a Recommendation* Appendix Table 2. GRADE Criteria Used for Grading the Overall Quality of Evidence In brief, the process involved reviewing the 2008 KDIGO guideline on HCV and CKD, as well as other HCV guidelines (American Association for the Study of Liver Diseases and Infectious Diseases Society of America [AASLD/IDSA], European Association for the Study of the Liver, and Japanese Society for Dialysis Therapy) that had sections related to CKD (68), and then developing research questions for each of the chapters. On the basis of specific research questions identified by the work group, the evidence review team conducted systematic reviews on 7 topics: HCV treatment in CKD populations (chapters 2, 4, and 5), pretransplant noninvasive testing for hepatic fibrosis (chapter 1), outcome of isolation of HCV-infected patients in hemodialysis units (chapter 3), outcomes with early versus late kidney transplantation for HCV-infected patients on the waitlist (chapter 4), transplantation of kidneys from HCV-infected donors to HCV-infected recipients (chapter 4), predictors of CKD progression associated with HCV (chapter 1), and relationships between HCV and graft loss and mortality in kidney transplant recipients (chapter 4). The search parameters are presented in Appendix Table 3. The formal literature search identified 125 eligible studies, which were summarized and assessed for quality by using the GRADE methodology (5). The work group then developed guideline statements rated as strong (level 1) or weak (level 2) on the basis of the strength of evidence from the systematic review as well as other evidence from non-CKD populations. In accordance with GRADE, the strength of the evidence supporting each guideline statement was rated from high (A) to very low (D). Guideline statements providing general guidance, and therefore not based on systematic evidence review, were labeled nongraded. Appendix Table 3. Research Questions Addressing the Systematic Update of Selected Recommendations The guideline statements and supporting text subsequently underwent external stakeholder review by individuals and organizations worldwide with expertise in the field. The final document incorporated comments and suggestions from the external review where appropriate. Chapter 1: Recommendations Related to the Detection and Evaluation of HCV in CKD 1.1.1. We recommend screening all patients for HCV infection at the time of initial evaluation of CKD (1C). 1.1.1.1. We recommend using an immunoassay followed by nucleic acid testing (NAT) if immunoassay is positive (1A). Hepatitis C virus infection is more prevalent among persons with CKD than it is in the general population. Approximately 5% of patients receiving incident dialysis have HCV-positive results on enzyme-linked immunosorbent assay (EIA) (9), compared with an estimated 1% of the general U.S. population (10). Recent studies implicated HCV infection as an independent risk factor for faster rates of CKD progression (11), related in part to the association of HCV with several glomerulonephritides but probably also independent of this connection. The AASLD/IDSA and CDC recommend 1-time HCV testing for the 1945 to 1965 birth cohort because of a higher prevalence of the virus in this group (6, 12). In addition, the AASLD/IDSA and CDC recommend HCV testing for high-risk patients, including those who have ever required long-term hemodialysis, have used injection or intranasal drugs, received a solid organ transplant before July 1992, have HIV infection, or were ever incarcerated (6) (Table 1). The recommendation to screen all patients for HCV at the time of initial CKD evaluation is based on these guideline recommendations, the higher prevalence of HCV infection among patients with CKD, and the more rapid CKD progression seen in patients with CKD and HCV infection compared with uninfected patients (13). Future studies should determine the degree of clinical benefit of this strategy of HCV testing in patients with CKD. Repeated HCV testing is prudent for patients who may be continuously exposed to HCV, such as through ongoing drug use or long-term hemodialysis. Decisions regarding the benefit of HCV screening in patients with CKD may be informed by a recent report describing a slower decrease in glomerular filtration rate (GFR) after versus before successful HCV treatment in patients with an estimated GFR less than 60 mL/min/1.73 m2 (14). Table 1. AASLD/IDSA Guidelines for 1-Time HCV Testing With a Focus on Recommendations Relevant to CKD Populations* Recommendations Related to HCV Testing in Patients With End-Stage Kidney Disease 1.1.2. We recommend screening all patients for HCV infection upon initiation of in-center hemodialysis or upon transfer from another dialysis facility or modality (1A). 1.1.2.1. We recommend using NAT alone or an immunoassay followed by NAT if immunoassay is positive (1A). 1.1.3. We suggest screening all patients for HCV infection upon initiation of peritoneal dialysis or home hemodialysis (2D). 1.1.4. We recommend screening all patients for HCV infection at the time of evaluation for kidney transplantation (1A). The prevalence of HCV in the hemodialysis population exceeds that of the general population, with approximately 10% of patients in the recent DOPPS (Dialysis Outcomes and Practice Patterns Study) analyses having positive results on EIA, also known as anti-HCV or HCV antibody testing (9, 15). The high HCV prevalence occurs as a result of the high prevalence of HCV on initiation of dialysis (9) as well as nosocomial transmission within hemodialysis units. Testing for HCV before the start of in-center hemodialysis (including a transition from another dialysis method) and upon transfer between hemodialysis facilities provides the opportunity to identify patients potentially exposed to HCV at the previous facility. Acute HCV infection in hemodialysis units is identified by monitoring liver biochemical test results for increases above baseline, which may suggest acute HCV infection and prompt testing for HCV viremia several months before EIA testing shows positive results. The recommendation for HCV testing in patients receiving peritoneal dialysis or home hemodialysis is based on limited evidence; nevertheless, it is a prudent approach. Testing for HCV is recommended for kidney transplant candidates to determine who is at risk for progressive hepatic disease and might benefit from an H