Craig E. Gordon, MD, MS; Marina C. Berenguer, MD; Wahid Doss, MD; Fabrizio Fabrizi, MD; Jacques Izopet, PharmD, PhD; Vivekanand Jha, MBBS, MD, DM; Nassim Kamar, MD, PhD; Bertram L. Kasiske, MD; Ching-Lung Lai, MD; José M. Morales, MD, PhD; Priti R. Patel, MD, MPH; Stanislas Pol, MD, MPH; Marcelo O. Silva, MD; Ethan M. Balk, MD, MPH; Amy Earley, BS; Mengyang Di, MD, PhD; Michael Cheung, MA; Michel Jadoul, MD*; Paul Martin, MD*
Note: The development of this guideline is strictly funded by KDIGO, and neither KDIGO nor its guideline work group members sought or received monies or fees from corporate or commercial entities in connection with this work.
Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Acknowledgment: The authors thank the KDIGO cochairs, David C. Wheeler and Wolfgang C. Winkelmayer, for their invaluable guidance. They also acknowledge all who provided feedback during the stakeholder review of the draft guideline.
Financial Support: This guideline is supported by KDIGO; no funding is accepted for the development of specific guidelines.
Disclosures: Dr. Gordon reports personal fees from AbbVie and Alexion outside the submitted work. Dr. Berenguer reports grants from Gilead and personal fees from AbbVie outside the submitted work. Dr. Fabrizi reports personal fees from AbbVie and MSD during the conduct of the study. Dr. Jha reports grants from Baxter Healthcare and GlaxoSmithKline, personal fees from NephroPlus, and advisory board membership at Zydus Cadilla and Biocon outside the submitted work. Dr. Kamar reports personal fees from MSD, Gilead, and AbbVie during the conduct of the study and personal fees from AbbVie, Amgen, Astellas, Chiesi, Fresenius, Gilead, Medical Care, Merck Sharp and Dohme, Neovii, Novartis, Roche, Sanofi, and Shire outside the submitted work. Dr. Lai reports personal fees from Gilead Sciences and AbbVie outside the submitted work. Dr. Pol reports personal fees from Gilead and Janssen, grants from Roche, and grants and personal fees from MSD and AbbVie during the conduct of the study. Dr. Silva reports grants, personal fees, and nonfinancial support from AbbVie, MSD, Gilead, and BMS during the conduct of the study. Dr. Jadoul reports personal fees from Astellas, GlaxoSmithKline, Vifor FMC Renal Pharma, AbbVie, Amgen, Menarini, and Nipro; grants from Alexion, Janssen-Cilag, Otsuka, and Roche; and grants and personal fees from Merck (MSD) outside the submitted work. Dr. Martin has served as a consultant for AbbVie, Merck, and Gilead. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-1539.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Catharine B. Stack, PhD, MS, Deputy Editor, Statistics, reports that she has stock holdings in Pfizer, Johnson & Johnson, and Colgate-Palmolive. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Corresponding Author: Craig Gordon, MD, MS, Division of Nephrology, Tufts Medical Center, 800 Washington Street, Box #391, Boston, MA 02111; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Gordon: Division of Nephrology, Tufts Medical Center, 800 Washington Street, Box #391, Boston, MA 02111.
Dr. Berenguer: Department of Gastroenterology, Hepatology and Liver Transplantation Unit, Hospital Universitari i Politecnic La Fe, Avenida Fernando Abril Martorell, 106, 46026 Valencia, Spain.
Dr. Doss: 12 Sarah El Gezira Street, Zamalek, Cairo 11211, Egypt.
Dr. Fabrizi: Divisione Nefrologica, Ospedale Maggiore, Padiglione Croff, Via Commenda 15, 20122 Milan, Italy.
Dr. Izopet: Laboratoire de virologie, Centre national de référence du virus de l'hépatite E, CHU Toulouse, Hôpital Purpan, 31300 Toulouse, France.
Dr. Jha: The George Institute for Global Health, 310–11 Splendor Forum, Jasola, New Delhi 110025, India.
Dr. Kamar: Department of Nephrology and Organ Transplantation, CHU Rangueil, TSA 50032, Cedex 9, Toulouse 31059, France.
Dr. Kasiske: Hennepin Healthcare Research Institute, Scientific Registry of Transplant Recipients, 701 Park Avenue, Suite S4.100, Minneapolis, MN 55415.
Dr. Lai: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road 102, Pokfulam, Hong Kong.
Dr. Morales: Healthcare Research Institute, Hospital 12 de Octubre, 28041 Madrid, Spain.
Dr. Patel: Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333.
Dr. Pol: Département d'Hépatologie, Hôpital Cochin, APHP, INSERM U1223, UMS-20, Institut Pasteur, Université Paris Descartes, Paris, France.
Dr. Silva: Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Avenida Juan D. Perón 1500, B1629AHJ Pilar, Provincia de Buenos Aires, Buenos Aires, Argentina.
Drs. Balk and Di: Center for Evidence Synthesis in Health, Box G-S121-8, Brown University School of Public Health, Providence, RI 02912.
Ms. Earley and Mr. Cheung: KDIGO, Avenue Louise 65, Suite 11, 1050 Brussels, Belgium.
Dr. Jadoul: Department of Nephrology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Avenue Hippocrate 10, 1200 Bruxelles, Belgium.
Dr. Martin: Division of Gastroenterology and Hepatology, University of Miami, Miller School of Medicine, 1120 Northwest 14th Street, Room 1115, Miami, FL 33136.
Author Contributions: Conception and design: F. Fabrizi, J. Izopet, B.L. Kasiske, C.L. Lai, J.M. Morales, S. Pol, E.M. Balk, A. Earley, M. Jadoul, P. Martin.
Analysis and interpretation of the data: M.C. Berenguer, F. Fabrizi, J. Izopet, V. Jha, N. Kamar, B.L. Kasiske, C.L. Lai, J.M. Morales, P.R. Patel, S. Pol, M.O. Silva, E.M. Balk, A. Earley, M. Di.
Drafting of the article: C.E. Gordon, F. Fabrizi, V. Jha, C.L. Lai, J.M. Morales, P.R. Patel, S. Pol, M.O. Silva, A. Earley.
Critical revision for important intellectual content: C.E. Gordon, M.C. Berenguer, W. Doss, F. Fabrizi, J. Izopet, V. Jha, N. Kamar, C.L. Lai, J.M. Morales, P.R. Patel, S. Pol, M.O. Silva, E.M. Balk, A. Earley, M. Di, M. Jadoul, P. Martin.
Final approval of the article: C.E. Gordon, M. Berenguer, W. Doss, F. Fabrizi, J. Izopet, V. Jha, N. Kamar, B.L. Kasiske, C.L. Lai, J.M. Morales, P.R. Patel, S. Pol, M.O. Silva, E.M. Balk, A. Earley, M. Di, M. Cheung, M. Jadoul, P. Martin.
Provision of study materials or patients: C.L. Lai, E.M. Balk.
Statistical expertise: E.M. Balk.
Administrative, technical, or logistic support: C.E. Gordon, A. Earley, M. Cheung.
Collection and assembly of data: F. Fabrizi, B.L. Kasiske, C.L. Lai, J.M. Morales, P.R. Patel, M.O. Silva, E.M. Balk, A. Earley, M. Di, M. Jadoul.
The Kidney Disease: Improving Global Outcomes (KDIGO) 2018 clinical practice guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in chronic kidney disease (CKD) is an extensive update of KDIGO's 2008 guideline on HCV infection in CKD. This update reflects the major advances since the introduction of direct-acting antivirals (DAAs) in the management of HCV infection in the CKD population.
The KDIGO work group tasked with developing the HCV and CKD guideline defined the scope of the guideline, gathered evidence, determined topics for systematic review, and graded the quality of evidence previously summarized by the evidence review team. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to appraise the quality of evidence and rate the strength of the recommendations. Searches of the English-language literature were conducted through May 2017 and were supplemented with targeted searches for studies of DAA treatment and with abstracts from nephrology, hepatology, and transplantation conferences. A review process involving many stakeholders, subject matter experts, and industry and national organizations informed the guideline's final modification.
The updated guideline comprises 66 recommendations. This synopsis focuses on 32 key recommendations pertinent to the prevention, diagnosis, treatment, and management of HCV infection in adult CKD populations.
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 albumin–creatinine 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.).
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
Appendix Table 3. Research Questions Addressing the Systematic Update of Selected Recommendations
Table 1. AASLD/IDSA Guidelines for 1-Time HCV Testing With a Focus on Recommendations Relevant to CKD Populations*
Treatment scheme for CKD GFR categories G1 to G5D.
Recommendation grades (1 or 2) and strength of evidence (A to D) are provided for each recommended treatment regimen and HCV genotype. Sofosbuvir/velpatasvir-based regimens are not shown here because they were not formally reviewed by the evidence review team at the time of guideline publication. However, these regimens may be considered in patients with CKD G1 to G3b given their availability in certain jurisdictions. + = positive results; CKD = chronic kidney disease; DAA = direct-acting antiviral; GFR = glomerular filtration rate; HCV = hepatitis C virus; NAT = nucleic acid testing.
Table 2. HCV Treatment Regimens for Patients With CKD and for Kidney Transplant Recipients*
Treatment scheme for kidney transplant recipients.
Recommendation grade (1 or 2) and strength of evidence (A to D) are provided for each recommended treatment regimen and HCV genotype. Sofosbuvir/velpatasvir-based regimens are not shown here because they were not formally reviewed by the evidence review team at the time of guideline publication. However, these regimens may be considered in kidney transplant recipients with a GFR ≥30 mL/min/1.73 m2 given their availability in certain jurisdictions. + = positive results; CKD = chronic kidney disease (T suffix in GFR categories [e.g., G1T] denotes transplant recipient); GFR = glomerular filtration rate; HCV = hepatitis C virus; NAT = nucleic acid testing.
University hospital, 80000 Amiens, France. email@example.com
October 24, 2019
Clinical Practice Guideline about Hepatitis C Virus Infection in Chronic Kidney Disease: cure and care!
The 2018 Clinical Practice Guideline about Hepatitis C Virus Infection in Chronic Kidney Disease deserved comment.(1)First, care for comorbid conditions should have required a special consideration with at least a recommendation. Innes et colleagues showed robust evidence that more than half the excess mortality risk for individuals with chronic hepatitis C in the US is due to health risk behaviours rather than chronic hepatitis C, (2) Multi-factorial life-style interventions by trained professionals have sustained beneficial effects over the long term,(3) they are too rarely provided by healthcare schemes, in contrast to costly pills. Second, considering the price of hepatitis C direct-acting antivirals and mind lines, a recommendation should have highlighted there are enough data now supporting the equal efficacy of originator and generic therapies.(4-5)Third, among the 32 key recommendations, 18 are graded 1A and only three graded 2. This deserved kudos as too frequently clinical guideline are an acknowledgment of ignorance, useless for clinical practice as recommendations about patient with Barrett's esophagus which are only based on weak evidence or expert opinion .(6-7) Last, the end of the literature searching for the last update of the guideline and for the last standard check should be provided. 1 Gordon CE, Berenguer MC, Doss W et al. 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. Ann Intern Med 2019. Online Sep 24. doi: 10.7326/M19-1539.2 Innes H, McAuley A, Alavi M, Valerio H, Goldberg D, Hutchinson SJ. The contribution of health risk behaviours to excess mortality in American adults with chronic hepatitis C: a populationcohort-study. Hepatology 2018;67:97–107. 3 Baumann S, Toft U, Aadahl M, Jørgensen T, Pisinger C. The long-term effect of a population-based life-style intervention on smoking and alcohol consumption. The Inter99 Study--a randomized controlled trial. Addiction 2015;110:1853-60.4 Hill A, Tahat L, Mohammed MK, et al. Bioequivalent pharmacokinetics for generic and originator hepatitis C direct-acting antivirals. J Virus Erad 2018; 4: 128–31.5 Gupta S, Rout G, Patel AH, et al. Efficacy of generic oral directly acting agents in patients with hepatitis C virus infection. J Viral Hepat 2018; 25: 771–78.6 Shaheen NJ, Falk GW, Iyer PG, Gerson LB. ACG Clinical Guideline: Diagnosis and management of Barrett's Esophagus. Am J Gastroenterol 2016;111:30-50.7 Braillon A. Screening and surveillance for Barrett’s esophagus: When will we reach the horizon? Am J Gastroenterol 2016 ;111:899-900.
Craig E Gordon, Michel Jadoul, Paul Martin
Tufts Medical Center, Universite Catholique de Louvain, University of Miami
November 18, 2019
We appreciate your thoughtful comments. We agree that the consideration of comorbidities has a key role in the management of HCV. Although there is no specific guideline statement addressing this issue independently, it is among the considerations recommended in the selection of HCV treatment regimen in guideline statements 2.1.2 and 2.4.2-- arguably 2 of the most important statements in the entire guideline. We agree also that the development of generic DAA therapies may be an important contribution given their lower cost; however, we hesitated to comment on these in this manuscript or in the original guidelines due to the lack of evidence in CKD populations. We appreciate your comments regarding the fairly high quality of evidence in the field of HCV treatment and we hope in the future even more evidence will be available. Finally, we realized we omitted the literature search cutoff dates in the text of this brief summary but the information is so noted in the original guideline document with the last search conducted in May 2017 and articles supplemented by the Work Group through July 2018.Craig E Gordon, Michel Jadoul, Paul MartinDr. Gordon: Division of Nephrology,Tufts Medical Center,800 Washington Street, Box #391, Boston, MA 02111.Dr. Jadoul: Department of Nephrology, Cliniques Universitaires Saint-Luc, Universite´ Catholique de Louvain, Avenue Hippocrate 10, 1200 Bruxelles, Belgium.Dr. Martin: Division of Gastroenterology and Hepatology, University of Miami, Miller School of Medicine, 1120 Northwest 14th Street, Room 1115, Miami, FL 33136.
University Hospital, 80000 Amiens. France
December 17, 2019
Thanks to Craig E Gordon, Michel Jadoul, Paul Martin
For their response to my comment. The Journal must be commended for providing a tool which allows to nurture scientific debate. Sadly, too many authors do not care about it yet.
Gordon CE, Berenguer MC, Doss W, et al. 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. Ann Intern Med. 2019;171:496–504. [Epub ahead of print 24 September 2019]. doi: https://doi.org/10.7326/M19-1539
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Published: Ann Intern Med. 2019;171(7):496-504.
Published at www.annals.org on 24 September 2019
Chronic Kidney Disease, Gastroenterology/Hepatology, Guidelines, Infectious Disease, Nephrology.
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