HCV Can and Should Be Eliminated From Dialysis Units

Abstract

Related Article, p. 511 Upon the identification of hepatitis C virus (HCV) over 3 decades ago, HCV infection was recognized as a frequent complication of maintenance hemodialysis (HD), in part owing to high rates of blood transfusion.1Jeffers L.J. Perez G.O. de Medina M.D. et al.Hepatitis C infection in two urban hemodialysis units.Kidney Int. 1990; 38: 320-322Abstract Full Text PDF PubMed Scopus (113) Google Scholar Progressive improvements in testing blood donors by serological tests (and more recently by nucleic acid testing [NAT]), the increasing use of erythropoiesis-stimulating agents, and the improvement of hygienic precautions all contributed over the subsequent 2 decades to a reduction in the incidence and prevalence of HCV in HD patients. Yet, HCV prevalence still averaged 9.9% in the Dialysis Outcomes and Practice Patterns Study (DOPPS) in 2012-2015, whereas incidence averaged 1.2 new cases per 100 patient-years.2Jadoul M. Bieber B.A. Martin P. et al.Prevalence, incidence, and risk factors for hepatitis C virus infection in hemodialysis patients.Kidney Int. 2019; 95: 939-947Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar Worldwide, this incidence translates to a minimum of 20,000 new cases yearly among patients on maintenance HD. The vast majority of cases are nosocomial,3Jadoul M. Transmission routes of HCV infection in dialysis.Nephrol Dial Transplant. 1996; 11: 36-38Crossref PubMed Scopus (55) Google Scholar resulting from substandard hygienic precautions, with a minority acquired outside the HD unit, mostly from intravenous drug use. These dire figures of incident HCV infection while on HD collide with the World Health Organization (WHO) vision to eliminate viral hepatitis as a public health problem by 2030.4World Health OrganizationGlobal health sector strategy on viral hepatitis 2016-2021.https://apps.who.int/iris/bitstream/handle/10665/246177/WHO-HIV-2016.06-eng.pdf;jsessionid=60A93ADD1A191FF6A0FA823314D24C43?sequence=1 (WHO, 2016)Date accessed: May 28, 2021Google Scholar The WHO commitment hinges upon the recent availability of extremely effective and safe direct-acting antiviral agents (DAAs). Indeed, cure of HCV infection is currently possible in almost every patient whose HCV infection is diagnosed. However, because HCV infection is frequently underdiagnosed in the general population, the concept of micro-elimination was developed5Lazarus J.V. Safreed-Harmon K. Thursz M.R. et al.The micro-elimination approach to eliminating hepatitis C: strategic and operational considerations.Semin Liver Dis. 2018; 38: 181-192Crossref PubMed Scopus (134) Google Scholar; this strategy targets individuals with diagnosed HCV infection who are under regular medical care, such as HD patients. Yet, despite the availability of effective and well-tolerated DAA regimens for HD patients,6Bruchfeld A. Roth D. Martin P. et al.Elbasvir plus grazoprevir in patients with hepatitis C virus infection and stage 4-5 chronic kidney disease: clinical, virological, and health-related quality-of-life outcomes from a phase 3, multicentre, randomised, double-blind, placebo-controlled trial.Lancet Gastroenterol Hepatol. 2017; 2: 585-594Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar,7Gane E. Lawitz E. Pugatch D. et al.Glecaprevir and pibrentasvir in patients with HCV and severe renal impairment.N Engl J Med. 2017; 377: 1448-1455Crossref PubMed Scopus (278) Google Scholar there has been hitherto little evidence that HCV elimination from HD units is underway. In this issue of AJKD, Hu et al8Hu T.H. Su W.W. Yang C.C. et al.Changhua Hepatitis C Elimination Task ForceElimination of hepatitis C virus in a dialysis population: a collaborative care model in Taiwan.Am J Kidney Dis. 2021; 78: 511-519Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar report a quality improvement initiative that describes the almost complete elimination of HCV from all 31 HD units of Changhua County in Taiwan. Importantly, Taiwan has a high HCV prevalence, largely as a result of transmission decades ago by health care delivered with suboptimal hygienic precautions.9Winston A. Wurcel A.G. Gordon C. Goyal N. Viral hepatitis in patients on hemodialysis.Semin Dial. 2020; 33: 254-262Crossref PubMed Scopus (2) Google Scholar Thus, Taiwanese authorities have prioritized meeting the WHO target as part of their public health policy and a collaborative care model was implemented. The dialysis population was the first target of a broader program aiming at covering other high-risk populations (people who inject drugs, prisoners, HIV-positive persons, etc). The major components of the first step of the collaborative care model included an emphasis on collaboration between gastroenterologists and nephrologists, access to DAAs (restricted to severe cases of HCV prior to 2019), nurse-led case management, easy access to medical transportation for patients to attend the HCV clinic, use of mobile clinics to reach remote areas, integration of county- and national-level data, and collaboration between central and local governments. A total of 3,657 dialysis patients (92.7% receiving HD), either prevalent at the time of study start or incident over the study period (January 1 to September 30, 2019), were included. A positive anti-HCV antibody test was recorded in 403 of 3,657 patients (11%). NAT was performed in 396 of 403 (98.3% diagnosis rate). Surprisingly, 176 of the antibody-positive patients were NAT negative, a higher proportion (44%) than in most dialysis studies, in which the proportion is only 10%-15%. This was explained by prior antiviral treatment in 65 patients and may represent false-positive antibody testing or spontaneous viral clearance from prior infection in the remaining 111 patients. Among the 216 viremic patients, 184 received a DAA regimen (mainly glecaprevir-pibrentasvir, or grazoprevir-elbasvir),6Bruchfeld A. Roth D. Martin P. et al.Elbasvir plus grazoprevir in patients with hepatitis C virus infection and stage 4-5 chronic kidney disease: clinical, virological, and health-related quality-of-life outcomes from a phase 3, multicentre, randomised, double-blind, placebo-controlled trial.Lancet Gastroenterol Hepatol. 2017; 2: 585-594Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar,7Gane E. Lawitz E. Pugatch D. et al.Glecaprevir and pibrentasvir in patients with HCV and severe renal impairment.N Engl J Med. 2017; 377: 1448-1455Crossref PubMed Scopus (278) Google Scholar whereas the remaining 32 patients were not treated for various reasons (previous DAA failure, n = 1; refusal, n = 14; too unstable, n = 8; death before DAA, n = 9). The SVR12 rate (equivalent to a cure) was 166 of 173 (96%) among patients completing the DAA regimen. These results demonstrate that the battle against HCV within HD units can be successful with multidisciplinary collaboration and adequate funding. Admittedly, some patients may have a too-short life expectancy to justify a DAA course,9Winston A. Wurcel A.G. Gordon C. Goyal N. Viral hepatitis in patients on hemodialysis.Semin Dial. 2020; 33: 254-262Crossref PubMed Scopus (2) Google Scholar,10Jadoul M. Berenguer M.C. Doss W. et al.Executive summary of the 2018 KDIGO Hepatitis C in CKD Guideline: welcoming advances in evaluation and management.Kidney Int. 2018; 94: 663-673Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar as illustrated by the 10% death rate over the relatively short study period. Thus, similar initiatives are urgently needed in other countries, including lower-income countries. Needless to say, the prerequisite is that actual HCV infection is diagnosed in HD patients by regular enzymatic immunoassay, followed, if positive, by NAT.10Jadoul M. Berenguer M.C. Doss W. et al.Executive summary of the 2018 KDIGO Hepatitis C in CKD Guideline: welcoming advances in evaluation and management.Kidney Int. 2018; 94: 663-673Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar,11Recommendations for Preventing Transmission of Infections Among Chronic Hemodialysis Patients.Centers for Disease Control and Prevention. 2001; 50: 1-43Google Scholar The next step in the cascade of care is starting a DAA regimen. Fortunately, the recent decision by the US Food and Drug Administration to extend the label of sofosbuvir-based therapies for use in patients with chronic kidney disease glomerular filtration rate categories 4-5,12Sise M.E. McQuaid T. Martin P. Sofosbuvir-based hepatitis C therapies in patients with chronic and end-stage kidney disease.Nephrol Dial Transplant. 2021; (doi:10.1093/ndt/gfab072)https://doi.org/10.1093/ndt/gfab072Crossref PubMed Scopus (2) Google Scholar including dialysis patients, is good news, as it broadens the spectrum of DAA regimens available in dialysis patients. In some countries either the original sofosbuvir or generic sofosbuvir may be available at a very affordable cost. Admittedly, the collaborative care model used in Taiwan will need to be tailored to the way dialysis care is provided in each context, depending on the breakdown of satellite vs hospital-based units and the presence of large dialysis organizations, among other factors. As in previous large-sized studies of HCV in HD (such as DOPPS), the study by Hu et al relied on the widely used serologic tests, rather than the gold-standard NAT. Thus, the actual prevalence of HCV infection probably has been slightly underestimated, as anti-HCV antibody testing remains negative for a median of 5 months after infection in HD patients.13Sypsa V. Psichogiou M. Katsoulidou A. et al.Incidence and patterns of hepatitis C virus seroconversion in a cohort of hemodialysis patients.Am J Kidney Dis. 2005; 45: 334-343Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar Still, the results convincingly demonstrate that the prevalence of HCV infection can be reduced to a level close to zero, much lower than in the general population of the corresponding country. The benefits of this dramatic reduction of the prevalence of HCV infection are multiple. First, the hepatic complications of chronic HCV infection will largely be prevented. Second, the prognosis of patients cured from HCV infection likely is improved independently of hepatic benefits. There is indeed a large body of evidence demonstrating that chronic HCV infection is associated with micro-inflammation and insulin resistance and contributes to an increased cardiovascular risk, and that curing HCV is associated with a reduction of this risk.14Pol S. Parlati L. Jadoul M. Hepatitis C virus and the kidney.Nat Rev Nephrol. 2019; 15: 73-86Crossref PubMed Scopus (40) Google Scholar Lastly, the incidence of HCV infection in HD will drop sharply because of the reduction of number of source (infective) patients, thus creating a virtuous cycle. Ultimately, regular testing for HCV, as performed in Taiwan and recommended by both the CDC11Recommendations for Preventing Transmission of Infections Among Chronic Hemodialysis Patients.Centers for Disease Control and Prevention. 2001; 50: 1-43Google Scholar and KDIGO,10Jadoul M. Berenguer M.C. Doss W. et al.Executive summary of the 2018 KDIGO Hepatitis C in CKD Guideline: welcoming advances in evaluation and management.Kidney Int. 2018; 94: 663-673Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar may no longer be needed in units from which HCV has been eradicated, except in patients starting HD. Testing every patient at dialysis initiation then would be particularly important; the prevalence of HCV at HD start is around 5% in countries with relevant DOPPS data (United States, United Kingdom, Germany, Italy, Spain, and Japan), substantially higher than in the general population of these nations, with this prevalence not changing much over 2000-2015.2Jadoul M. Bieber B.A. Martin P. et al.Prevalence, incidence, and risk factors for hepatitis C virus infection in hemodialysis patients.Kidney Int. 2019; 95: 939-947Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar Patients found to be anti-HCV antibody and NAT positive at dialysis initiation could be treated immediately and this would obviate the isolation policy for HCV-positive patients used in Taiwan8Hu T.H. Su W.W. Yang C.C. et al.Changhua Hepatitis C Elimination Task ForceElimination of hepatitis C virus in a dialysis population: a collaborative care model in Taiwan.Am J Kidney Dis. 2021; 78: 511-519Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar and several other countries2Jadoul M. Bieber B.A. Martin P. et al.Prevalence, incidence, and risk factors for hepatitis C virus infection in hemodialysis patients.Kidney Int. 2019; 95: 939-947Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar that is burdensome, has been shown to be neither necessary nor effective, and is not currently recommended by either the CDC or the KDIGO guideline.10Jadoul M. Berenguer M.C. Doss W. et al.Executive summary of the 2018 KDIGO Hepatitis C in CKD Guideline: welcoming advances in evaluation and management.Kidney Int. 2018; 94: 663-673Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar,11Recommendations for Preventing Transmission of Infections Among Chronic Hemodialysis Patients.Centers for Disease Control and Prevention. 2001; 50: 1-43Google Scholar Importantly, this policy of testing at HD initiation should not preclude testing patients returning from vacations during which they received treatment in another unit, especially in a high-prevalence country,15Bhattacharya S. Price N. Boxall E. et al.Holiday haemodialysis and imported hepatitis C virus infection: a series of sixteen cases in two large haemodialysis units.J Clin Virol. 2009; 45: 296-299Crossref PubMed Scopus (23) Google Scholar as well as in those with risk factors for acquiring HCV outside of the dialysis setting. In summary, Hu and colleagues should be congratulated for showing us the way: this is the right time to eradicate HCV from HD units. Their success sounds as a call for urgent action by all HD units and providers. Michel Jadoul, MD, Laura Labriola, MD, and Craig E. Gordon, MD, MS. None. Prof Jadoul reports an unrestricted educational grant from Merck; having been a consultant for Merck and a speaker for Abbvie and Merck; and serving as KDIGO cochair. The other authors declare that they have no relevant financial interests. Received June 1, 2021 in response to an invitation from the journal. Accepted June 3, 2021 after editorial review by an Associate Editor and a Deputy Editor.