About this Journal Submit a Manuscript Table of Contents
Hepatitis Research and Treatment
Volume 2012 (2012), Article ID 832021, 4 pages
http://dx.doi.org/10.1155/2012/832021
Research Article

Hepatitis C Virus Core Antigen Test in Monitoring of Dialysis Patients

1Nephrology and Dialysis, ARNAS Civico and Di Cristina Hospital, Via Francesco Cilea 43, 90144 Palermo, Italy
2Microbiology and Virology, ARNAS Civico and Di Cristina Hospital, Palermo, Italy

Received 16 July 2012; Revised 10 November 2012; Accepted 11 November 2012

Academic Editor: Mikio Zeniya

Copyright © 2012 Gioacchino Li Cavoli et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Hepatitis C virus infection is a persistent worldwide public health concern. The prevalence of HCV infection is much higher in patients on chronic haemodialysis (HD) than in the general population. HCV infection can detrimentally affect patients throughout the spectrum of chronic kidney disease. Despite the control of blood products, hepatitis C virus transmission is still being observed among patients undergoing dialysis. Detection systems for serum HCV antibodies are insensitive in the acute phase because of the long serological window. Direct detection of HCV depends on PCR test but this test is not suitable for routine screening. Recent studies have highlighted the importance of HCV core antigen detection as an alternative to PCR. Few studies exist about the efficacy of HCV core antigen test in dialysis population. We studied the utility of HCV core antigen test in routine monitoring of virological status of dialysis patients. We screened 92 patients on long-term dialysis both by PCR HCV-RNA and HCV core antigen test. The sensitivity of HCVcAg test was 90%, the specificity 100%, the positive predictive power 100%, the negative predictive power 97%, and the accuracy 97%. We think serological detection of HCV core antigen may be an alternative to NAT techniques for routine monitoring of patients on chronic dialysis.

1. Introduction

Hepatitis C virus (HCV) infection is a persistent public health concern. HCV infects approximately 170 million people worldwide [1]. The prevalence of HCV infection is much higher in patients on chronic haemodialysis (HD) than in the general population. The estimated prevalence of HCV infection in HD patients is 7.8% in the USA [2], 5.2% in Germany [3], and 10% in Japan [4]. A recent study from Australia and New Zealand [5] in HD patients (n = 23,046) reported an independent and significant association between anti-HCV positive serologic status and all-cause mortality over a 10-year followup (HR, 1.25, 95% CI 1.07–1.46, ). Despite the control of blood products, HCV transmission is still being observed among HD patients. HCV infection is usually diagnosed based on the detection of anti-HCV antibody, while it goes undetected in the first 4–6 weeks of infection (so-called window period). Furthermore, patients positive for anti-HCV antibody include both those who are actively infected and those who have recovered from infection [6]. Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines for the prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease [7] recommended the use of nucleic acid amplification technology (NAT). A quantitative HCV core antigen (HCVcAg) test has been developed for the confirmation of viremia in patients with hepatitis C. This test can detect total nucleocapsid core antigen whose sequence is highly conserved across HCV genotypes. Some studies in the general population have highlighted the importance of HCVcAg detection as an alternative to NAT for early diagnosis of infection, as direct marker of viral replication in chronic phase of infection and as relevant marker for predicting and monitoring the response to therapy [8]. Few studies exist about the efficacy of HCVcAg test in patients on chronic HD in the early diagnosis of HCV infection [911]. The aim of this study is to apply these diagnostic advances in routine monitoring of chronic dialysis patients.

2. Materials and Methods

From September 2009 to February 2010 in our dialysis ward we included NAT and HCVcAg testing in the current clinical practice. Then we reviewed the medical records evaluating the virological monitoring. We evaluated 92 patients on long-term dialysis; among these subjects, 67 were on haemodialysis three times per week and 25 on peritoneal dialysis. We evaluated HCVcAg and HCVAb by chemiluminescent assay (Architect Abbott), HCV immunoblotting by InnoLia, HCVRNA by PCR (TaqMan Roche), viral genotype by INNO-LiPA 2.0, and other routine tests. Demographic and clinical characteristics of screened patients are given in Table 1.

tab1
Table 1: Demographic and clinical characteristics of 92 patients screened.

3. Results

We detected 66 HCVAb-negative and 26 HCVAb-positive patients. All HCVAb-negative subjects were both HCV-RNA negative and HCVcAg negative. Among 26 HCVAb-positive patients, 6 were both HCVcAg negative and HCV-RNA negative: 4 of these were immunoblotting negative and 2 immunoblotting positive; we considered in these 6 patients the current absence of HCV infection as in HCVAb negative subjects. Finally serum HCVRNA was detectable in 20 HCVAb-positive patients (Table 2). The results of liver function tests were unremarkable.

tab2
Table 2: Principal features of 20 HCVRNA positive patients.

Among 20 HCVRNA positive subjects, 2 were HCVcAg negative and 18 positive; the minimum HCVRNA IU/HCVAg pg ratio was 78; the maximum was 425.000 and the mean was 64.401. Therefore, in 18 out of 92 screened patients, HCVcAg test was positive (Table 3).

tab3
Table 3: Comparison between HCVcAg and PCR HCV-RNA test.

4. Discussion

HCV infection continues to be the most frequently recognized cause of liver damage in patients with CKD [12]. Although a severe clinical course of HCV-related liver disease seems unusual in most HD patients and cirrhosis is an infrequent event among dialysis patients, longitudinal studies have found an independent and significant relationship between anti-HCV antibody positivity and reduced patient survival [13, 14].

The Dialysis Outcomes and Practice Patterns Study (DOPPS) on HD patients in three continents [15] had reported an independent and significant association between positive anti-HCV antibody and mortality risk (adjusted relative risk, 1.17; ).

Fabrizi et al. showed that HCV-seropositive HD patients had higher rates of liver disease-related death than their seronegative counterparts, but that cardiovascular and infectious disease-related mortality rates were similar [16]. Ohsawa et al. showed that seropositivity for anti-HCVcAg is independently associated with increased all-cause, cardiovascular, and liver disease-related mortality in HD patients [17].

It is important to diagnose a hepatitis C virus infection in the acute phase in order to reduce the incidence of this infection in high-risk populations like HD patients [18]. Biochemical evaluation of HCV infection in patients with CKD is inaccurate. Serum aminotransferase values are typically lower in dialysis patients than the nonuremic populations [19]. Detection systems for serum HCV antibodies are insensitive in the acute phase because of the long serological window. The direct detection of HCV depends on NAT techniques with several problems: frequent unavailability, considerable skill requirement, limited reproducibility, and overall important costs. HCV detection by PCR-RNA, although widely accepted as a gold standard test in the diagnosis of HCV infection in CKD patients, is not suitable for routine screening. Recently HCVcAg quantification assay has proved useful for an early diagnosis of HCV infection in community-based and in dialysis populations. HCVcAg may be an alternative to HCV-RNA detection, since no subjects, who were negative for HCVcAg, were positive for HCV-RNA in a large population-based cohort study of Ohsawa et al. [20]; a recent study of Kato et al. also suggests that detection of HCVcAg combined with anti-HCV antibody is useful in predicting long-term survival prognosis of persistent HCV infection in HD patients [21].

According to our experience HCVcAg test is both a cost-effective (a single sample has a 120$ charge for PCR HCVRNA and a 20$ charge for HCVAg test) and a less labour-intensive alternative to NAT tests. These features make this assay useful for routine of chronic dialysis treatment patients.

5. Conclusions

Serological detection of HCVcAg may be an alternative to NAT techniques for routine monitoring of patients on chronic dialysis towards the prevention of HCV spread. It is an accurate marker for early identification of HCV infection; it can improve virological monitoring and integrate the diagnosis of acute hepatitis C in dialysis population. The minimal cost and its easiness make this assay useful for routine long-term dialysis treatment patients. These findings suggest that HCVcAg is applicable for clinical use as an alternative to NAT test.

Conflict of Interests

The authors declare that they have no conflict of interests.

References

  1. Centers for Disease Control and Prevention, “Recommendations for preventing transmission of infections among chronic haemodialysis patients,” Morbidity and Mortality Weekly Report, vol. 50, pp. 1–43, 2001.
  2. L. Finelli, J. T. Miller, J. I. Tokars, M. J. Alter, and M. J. Arduino, “National surveillance of dialysis-associated diseases in the United States, 2002,” Seminars in Dialysis, vol. 18, no. 1, pp. 52–61, 2005. View at Publisher · View at Google Scholar · View at Scopus
  3. R. S. Ross, S. Viazov, R. Clauberg et al., “Lack of de novo hepatitis C virus infections and absence of nosocomial transmissions of GB virus C in a large cohort of German haemodialysis patients,” Journal of Viral Hepatitis, vol. 16, no. 4, pp. 230–238, 2009. View at Publisher · View at Google Scholar · View at Scopus
  4. S. Nakai, K. Suzuki, I. Masakane et al., “Overview of regular dialysis treatment in Japan (as of 31 December 2008),” Therapeutic Apheresis and Dialysis, vol. 14, no. 6, pp. 505–540, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. D. R. Scott, J. K. W. Wong, T. S. Spicer et al., “Adverse impact of hepatitis C virus infection on renal replacement therapy and renal transplant patients in Australia and New Zealand,” Transplantation, vol. 90, no. 11, pp. 1165–1171, 2010. View at Publisher · View at Google Scholar · View at Scopus
  6. S. Laperche, N. Le Marrec, A. Girault et al., “Simultaneous detection of hepatitis C virus (HCV) core antigen and anti-HCV antibodies improves the early detection of HCV infection,” Journal of Clinical Microbiology, vol. 43, no. 8, pp. 3877–3883, 2005. View at Publisher · View at Google Scholar · View at Scopus
  7. “KDIGO clinical practice guidelines for the prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease,” Kidney International, vol. 73, pp. S1–S99, 2008.
  8. P. Veillon, C. Payan, G. Picchio, M. Maniez-Montreuil, P. Guntz, and F. Lunel, “Comparative evaluation of the total hepatitis C virus core antigen, branched-DNA, and amplicor monitor assays in determining viremia for patients with chronic hepatitis C during interferon plus ribavirin combination therapy,” Journal of Clinical Microbiology, vol. 41, no. 7, pp. 3212–3220, 2003. View at Publisher · View at Google Scholar · View at Scopus
  9. F. Fabrizi, G. Lunghi, F. Aucella et al., “Novel assay using total hepatitis C virus (HCV) core antigen quantification for diagnosis of HCV infection in dialysis patients,” Journal of Clinical Microbiology, vol. 43, no. 1, pp. 414–420, 2005. View at Publisher · View at Google Scholar · View at Scopus
  10. N. Bouzgarrou, I. Fodha, S. Ben Othman et al., “Evaluation of a total core antigen assay for the diagnosis of hepatitis C virus infection in hemodialysis patients,” Journal of Medical Virology, vol. 77, no. 4, pp. 502–508, 2005. View at Publisher · View at Google Scholar · View at Scopus
  11. M. Miedouge, K. Saune, N. Kamar, M. Rieu, L. Rostaing, and J. Izopet, “Analytical evaluation of HCV core antigen and interest for HCV screening in haemodialysis patients,” Journal of Clinical Virology, vol. 48, no. 1, pp. 18–21, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. C. O. Stehman-Breen, S. Emerson, D. Gretch, and R. J. Johnson, “Risk of death among chronic dialysis patients infected with hepatitis C virus,” American Journal of Kidney Diseases, vol. 32, no. 4, pp. 629–634, 1998. View at Scopus
  13. E. Nakayama, T. Akiba, F. Marumo, and C. Sato, “Prognosis of anti-hepatitis C virus antibody-positive patients on regular hemodialysis therapy,” Journal of the American Society of Nephrology, vol. 11, no. 10, pp. 1896–1902, 2000. View at Scopus
  14. M. Espinosa, A. Martin-Malo, M. A. A. De Lara, and P. Aljama, “Risk of death and liver cirrhosis in anti-HCV-positive long-term haemodialysis patients,” Nephrology Dialysis Transplantation, vol. 16, no. 8, pp. 1669–1674, 2001. View at Scopus
  15. D. A. Goodkin, J. L. Bragg-Gresham, K. G. Koenig et al., “Association of comorbid conditions and mortality in hemodialysis patients in Europe, Japan, and the United States: the Dialysis Outcomes and Practice Patterns Study (DOPPS),” Journal of the American Society of Nephrology, vol. 14, no. 12, pp. 3270–3277, 2003. View at Publisher · View at Google Scholar · View at Scopus
  16. F. Fabrizi, B. Takkouche, G. Lunghi, V. Dixit, P. Messa, and P. Martin, “The impact of hepatitis C virus infection on survival in dialysis patients: meta-analysis of observational studies,” Journal of Viral Hepatitis, vol. 14, no. 10, pp. 697–703, 2007. View at Publisher · View at Google Scholar · View at Scopus
  17. M. Ohsawa, K. Kato, K. Tanno, et al., “Seropositivity for anti-HCV core antigen is independently associated with increased all-cause, cardiovascular, and liver disease-related mortality in hemodialysis patients,” Journal of Epidemiology, vol. 21, no. 6, pp. 491–499, 2011.
  18. A. Di Napoli, P. Pezzotti, D. Di Lallo, N. Petrosillo, C. Trivelloni, and S. Di Giulio, “Epidemiology of hepatitis C virus among long-term dialysis patients: a 9-year study in an Italian region,” American Journal of Kidney Diseases, vol. 48, no. 4, pp. 629–637, 2006. View at Publisher · View at Google Scholar · View at Scopus
  19. F. Fabrizi, V. Dixit, P. Messa, and P. Martin, “Hepatitis C- related liver disease in dialysis patients,” in Hepatitis C in Renal Disease, Hemodialysis and Transplantation. Contributions to Nephrology, J. M. Morales, Ed., vol. 176, pp. 42–53, Karger, Basel, Switzerland, 2012.
  20. M. Ohsawa, K. Kato, K. Itai et al., “Standardized prevalence ratios for chronic hepatitis C virus infection among adult Japanese hemodialysis patients,” Journal of Epidemiology, vol. 20, no. 1, pp. 30–39, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. A. Kato, T. Takita, M. Furuhashi, T. Fujimoto, H. Suzuki, and Y. Maruyama, “Association of HCV core antigen seropositivity with long-term mortality in patients on regular hemodialysis,” Nephron Extra, vol. 2, pp. 76–86, 2012.