2018 Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C in Chronic Kidney Disease Guideline Implementation: Asia Summit Conference Report

Abstract

In 2018, Kidney Disease: Improving Global Outcomes (KDIGO) published a clinical practice guideline on the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in chronic kidney disease (CKD). The guideline synthesized recent advances, especially in HCV therapeutics and diagnostics, and provided clinical recommendations and suggestions to aid healthcare providers and improve care for CKD patients with HCV. To gain insight into the extent that the 2018 guideline has been adopted in Asia, KDIGO convened an HCV Implementation Summit in Hong Kong. Participants included nephrologists, hepatologists, and nurse consultants from 8 Southeast Asian countries or regions with comparable high-to-middle economic ranking by the World Bank: mainland China, Hong Kong, Japan, Malaysia, Singapore, South Korea, Taiwan, and Thailand. Through presentations and discussions, meeting participants described regional practice patterns related to the KDIGO HCV in CKD guideline, identified barriers to implementing the guideline, and developed strategies for overcoming the barriers in Asia and around the world. In 2018, Kidney Disease: Improving Global Outcomes (KDIGO) published a clinical practice guideline on the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in chronic kidney disease (CKD). The guideline synthesized recent advances, especially in HCV therapeutics and diagnostics, and provided clinical recommendations and suggestions to aid healthcare providers and improve care for CKD patients with HCV. To gain insight into the extent that the 2018 guideline has been adopted in Asia, KDIGO convened an HCV Implementation Summit in Hong Kong. Participants included nephrologists, hepatologists, and nurse consultants from 8 Southeast Asian countries or regions with comparable high-to-middle economic ranking by the World Bank: mainland China, Hong Kong, Japan, Malaysia, Singapore, South Korea, Taiwan, and Thailand. Through presentations and discussions, meeting participants described regional practice patterns related to the KDIGO HCV in CKD guideline, identified barriers to implementing the guideline, and developed strategies for overcoming the barriers in Asia and around the world. People with CKD have an elevated risk of developing chronic HCV infection.1Fabrizi F. Verdesca S. Messa P. et al.Hepatitis C virus infection increases the risk of developing chronic kidney disease: a systematic review and meta-analysis.Dig Dis Sci. 2015; 60: 3801-3813Crossref PubMed Scopus (74) Google Scholar, 2Zhang H. Xu H. Wu R. et al.Association of hepatitis C and B virus infection with CKD and impact of hepatitis C treatment on CKD.Sci Rep. 2019; 9: 1910Crossref PubMed Scopus (6) Google Scholar, 3Goel A. Bhadauria D.S. Aggarwal R. Hepatitis C virus infection and chronic renal disease: a review.Indian J Gastroenterol. 2018; 37: 492-503Crossref PubMed Scopus (5) Google Scholar, 4Chen Y.C. Chiou W.Y. Hung S.K. et al.Hepatitis C virus itself is a causal risk factor for chronic kidney disease beyond traditional risk factors: a 6-year nationwide cohort study across Taiwan.BMC Nephrol. 2013; 14: 187Crossref PubMed Scopus (31) Google Scholar Chronic HCV infection in the setting of CKD can accelerate decline of kidney function, increase the risk of kidney failure,5Lee J.J. Lin M.Y. Chang J.S. et al.Hepatitis C virus infection increases risk of developing end-stage renal disease using competing risk analysis.PLoS One. 2014; 9e100790Crossref PubMed Scopus (87) Google Scholar, 6Molnar M.Z. Alhourani H.M. Wall B.M. et al.Association of hepatitis C viral infection with incidence and progression of chronic kidney disease in a large cohort of US veterans.Hepatology. 2015; 61: 1495-1502Crossref PubMed Scopus (122) Google Scholar, 7Park H. Adeyemi A. Henry L. et al.A meta-analytic assessment of the risk of chronic kidney disease in patients with chronic hepatitis C virus infection.J Viral Hepat. 2015; 22: 897-905Crossref PubMed Scopus (63) Google Scholar, 8Park H. Chen C. Wang W. 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: 492-504Crossref PubMed Scopus (41) Google Scholar and increase the likelihood of mortality in dialysis patients.9Fabrizi F. Takkouche B. Lunghi G. et al.The impact of hepatitis C virus infection on survival in dialysis patients: meta-analysis of observational studies.J Viral Hepat. 2007; 14: 697-703PubMed Google Scholar Fortunately, effective treatment for HCV decreases the incidence of CKD8Park H. Chen C. Wang W. 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: 492-504Crossref PubMed Scopus (41) Google Scholar and improves kidney and cardiovascular outcomes in patients with diabetes.10Hsu Y.C. Lin J.T. Ho H.J. et al.Antiviral treatment for hepatitis C virus infection is associated with improved renal and cardiovascular outcomes in diabetic patients.Hepatology. 2014; 59: 1293-1302Crossref PubMed Scopus (194) Google Scholar In 2008, KDIGO published the first comprehensive clinical practice guideline on the diagnosis, prevention, and treatment of HCV in CKD.11Kidney Disease: Improving Global Outcomes HCV Work GroupKDIGO Clinical Practice Guidelines for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease.Kidney Int Suppl. 2008; : S1-S99Google Scholar At that time, treatment options for HCV in CKD G4 and G5 were limited to interferon with or without ribavirin. Because both interferon and ribavirin are eliminated by the kidney, dose reductions are necessary in patients with advanced CKD. Additionally, interferon and ribavirin have poor efficacy and tolerability, especially in patients undergoing dialysis.9Fabrizi F. Takkouche B. Lunghi G. et al.The impact of hepatitis C virus infection on survival in dialysis patients: meta-analysis of observational studies.J Viral Hepat. 2007; 14: 697-703PubMed Google Scholar In the past decade, oral antiviral therapies that directly target HCV replication have become available, with high efficacy rates and good tolerability profiles. Several regimens without interferon and ribavirin have been approved for use in patients with HCV infection and an estimated glomerular filtration rate <30 ml/min per 1.73 m2, including those on dialysis.12European Association for the Study of the LiverEASL recommendations on treatment of hepatitis C 2018.J Hepatol. 2018; 69: 461-511Abstract Full Text Full Text PDF PubMed Scopus (987) Google Scholar,13American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD/IDSA)HCV guidance: recommendations for testing, managing, and treating hepatitis C.https://www.hcvguidelines.org/Date accessed: July 17, 2019Google Scholar Diagnostic methods for determining severity of liver disease have also expanded, and the extent of liver fibrosis can now be assessed using non-invasive measures such as transient elastography.12European Association for the Study of the LiverEASL recommendations on treatment of hepatitis C 2018.J Hepatol. 2018; 69: 461-511Abstract Full Text Full Text PDF PubMed Scopus (987) Google Scholar,13American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD/IDSA)HCV guidance: recommendations for testing, managing, and treating hepatitis C.https://www.hcvguidelines.org/Date accessed: July 17, 2019Google Scholar Given the advances in diagnostics and therapeutics, a comprehensive update of the KDIGO HCV in CKD guideline was undertaken and published in 2018.14Kidney Disease: Improving Global Outcomes Hepatitis C Work GroupKDIGO 2018 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease.Kidney Int Suppl (2011). 2018; 8: 91-165Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar Multiple factors influence the extent of guideline incorporation into clinical practice, such as government health policies, drug availability, reimbursement policies, local economic determinants, and regulatory decisions. KDIGO, in collaboration with the Chinese University of Hong Kong and the Prince of Wales Hospital, Hong Kong, organized the first HCV Guideline Implementation Summit in May 2019 in Hong Kong. The goal of the summit was to understand practice patterns for preventing and managing HCV in CKD in 8 Southeast Asian countries or regions with comparable high or middle economic ranking by the World Bank.15Prasad N. Jha V. Hemodialysis in Asia.Kidney Dis (Basel). 2015; 1: 165-177Crossref PubMed Google Scholar Nephrologists, hepatologists, and nurse consultants from mainland China, Hong Kong, Japan, Malaysia, Singapore, South Korea, Taiwan, and Thailand attended the meeting and contributed to discussion. Meeting participants shared information related to the availability and reimbursement of direct-acting antiviral (DAA) therapies in each country or region, the current uptake and implementation of the KDIGO HCV in CKD guideline, as well as specific barriers to implementation. Finally, strategies aimed at overcoming these barriers and improving quality of care were developed. Globally, approximately 70 million people have chronic infection with HCV.16World Health Organization (WHO)Hepatitis C fact sheet.http://www.who.int/news-room/fact-sheets/detail/hepatitis-cDate accessed: May 16, 2019Google Scholar Prevalence rates vary throughout the world, as well as throughout East and Southeast Asia.17Gower E. Estes C. Blach S. et al.Global epidemiology and genotype distribution of the hepatitis C virus infection.J Hepatol. 2014; 61: S45-S57Abstract Full Text Full Text PDF PubMed Scopus (1235) Google Scholar Gower et al. reported in 2014 an estimated prevalence of HCV RNA positivity of 3.3% in Taiwan, 1.7% in Thailand, 1.1% in Japan and Malaysia, 0.8% in mainland China, 0.4% in the Republic of Korea, and 0.3%–0.5% in Hong Kong.17Gower E. Estes C. Blach S. et al.Global epidemiology and genotype distribution of the hepatitis C virus infection.J Hepatol. 2014; 61: S45-S57Abstract Full Text Full Text PDF PubMed Scopus (1235) Google Scholar HCV genotype distribution also varies throughout Asia. For example, HCV genotype 3 infection is more prevalent in Malaysia (59%) and Thailand (44%) compared with other regions in Asia and with the global population (22%).17Gower E. Estes C. Blach S. et al.Global epidemiology and genotype distribution of the hepatitis C virus infection.J Hepatol. 2014; 61: S45-S57Abstract Full Text Full Text PDF PubMed Scopus (1235) Google Scholar In patients with kidney failure, dialysis modality is an independent predictor of the likelihood of acquiring HCV infection, with hemodialysis (HD) being associated with a higher risk of HCV infection than peritoneal dialysis.18Johnson D.W. Dent H. Yao Q. et al.Frequencies of hepatitis B and C infections among haemodialysis and peritoneal dialysis patients in Asia-Pacific countries: analysis of registry data.Nephrol Dial Transplant. 2009; 24: 1598-1603Crossref PubMed Scopus (106) Google Scholar Internationally, HCV seroprevalence and seroconversion rates among dialysis patients vary widely, suggesting a need for consistent, rigorous local infection control measures. We have updated HCV prevalence in the 8 Southeast Asian countries and regions participating in the summit (Figure 1). Overall, the HCV prevalence in the HD population as determined by anti-HCV antibody testing ranges from 0.9% in Hong Kong to 13% in Taiwan. The HCV prevalence in peritoneal dialysis patients is lower than that in their HD counterparts, ranging from 0.8% in Hong Kong and China to 5% in Taiwan (Figure 1). Since the HCV prevalence data were largely based on anti-HCV antibody positivity rather than HCV RNA positivity, some of the anti–HCV-positive patients may in fact have been cured of HCV after DAA therapy despite harboring anti-HCV antibodies (e.g., Taiwan). In a pre-meeting survey, approximately 75% of 20 respondents indicated that their country or region has local guidelines on treating HCV in patients with CKD or on dialysis. Fewer than 20% indicated that there are critical differences between the local guidelines and the KDIGO HCV in CKD guideline. Indeed, participants indicated that all regions follow most of the guidance put forth by the KDIGO HCV in CKD guideline, as described below. Consistent with the KDIGO HCV in CKD guideline, all participating regions reported screening for HCV using an anti-HCV enzyme-linked immunosorbent assay followed by nucleic acid testing if the assay was positive. Because of its relatively low cost, this anti-HCV assay will likely remain the initial screening test for patients on HD in most regions. In Malaysia, where polymerase chain reaction analysis is available in only a few central laboratories, the HCV core antigen test is being considered as an alternative to nucleic acid testing because HCV core antigen testing costs less and allows confirmatory evaluation to be decentralized. Given that HCV core antigen has a detection threshold of at least 3000 IU/ml, and most patients with HCV have high levels of viremia, good concordance between HCV core antigen and polymerase chain reaction has been demonstrated.19Freiman J.M. Tran T.M. Schumacher S.G. et al.Hepatitis C core antigen testing for diagnosis of hepatitis C virus infection: a systematic review and meta-analysis.Ann Intern Med. 2016; 165: 345-355Crossref PubMed Scopus (93) Google Scholar, 20Chevaliez S. Soulier A. Poiteau L. et al.Clinical utility of hepatitis C virus core antigen quantification in patients with chronic hepatitis C.J Clin 2014; 61: PubMed Scopus Google Scholar, N. et evaluation of HCV core antigen and for HCV screening in haemodialysis Clin PubMed Scopus Google Scholar HCV core antigen is available in Hong Kong and is relatively in and mainland For HD all of the participating regions HCV screening at with the KDIGO HCV in CKD guideline. In Taiwan, HCV screening of HD patients is because of reimbursement In Singapore, HD patients are 3 a practice in to an of of HCV infection in the renal at in of of a Hepatitis C in accessed: July 2019Google Scholar all participating regions reported that nucleic acid testing is for patients are on HD and have or have after is Malaysia, where nucleic acid testing is in the of HCV The KDIGO HCV in CKD guideline that all CKD patients with HCV be considered for treatment with an treatment for patients with CKD G4 or G5 HD is for all HCV or for HCV and (Figure Disease: Improving Global Outcomes Hepatitis C Work GroupKDIGO 2018 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease.Kidney Int Suppl (2011). 2018; 8: 91-165Abstract Full Text Full Text PDF PubMed Scopus (78) Google N. S. et treatment in liver or kidney patients with hepatitis C virus 2018; PubMed Scopus Google Scholar At the of HCV in CKD KDIGO guideline and the HCV in CKD Asia regimens were for CKD G4 or G5 glomerular filtration rate ml/min per 1.73 Association for the Study of the LiverEASL recommendations on treatment of hepatitis C 2018.J Hepatol. 2018; 69: 461-511Abstract Full Text Full Text PDF PubMed Scopus (987) Google Scholar,13American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD/IDSA)HCV guidance: recommendations for testing, managing, and treating hepatitis C.https://www.hcvguidelines.org/Date accessed: July 17, 2019Google Scholar in the US and the of to CKD G4 and G5 patients and those on dialysis. regimens may a treatment in countries where are available, this is as limited to the US and is based on data and rather than on was as a treatment in HCV genotype and patients with CKD G4 or Disease: Improving Global Outcomes Hepatitis C Work GroupKDIGO 2018 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease.Kidney Int Suppl (2011). 2018; 8: 91-165Abstract Full Text Full Text PDF PubMed Scopus (78) Google G. A. et and efficacy of and in hepatitis C patients with renal PubMed Scopus Google Scholar, G. A. et and of and therapy in chronic hemodialysis patients with chronic hepatitis C.J Gastroenterol. 2016; PubMed Scopus Google Scholar, H. et and efficacy of direct-acting antiviral therapy and for chronic hepatitis C virus genotype infection in patients on Gastroenterol. 2016; PubMed Scopus (63) Google Scholar, et and of and in patients with hepatitis C virus genotype infection on 2019; PubMed Scopus Google Scholar, G. N. H. et and in hemodialysis patients with hepatitis C virus infection: a nationwide study in Gastroenterol. 2018; PubMed Scopus Google Scholar from Japan that has efficacy genotype F. N. 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