Departments of Nephrology, 1Cliniques Universitaires St. Luc, Université catholique de Louvain, Brussels, Belgium, 2Centre Médical E. Rist, Paris, France, 3Western Infirmary, Glasgow, UK, 4A. Manzoni Hospital, Lecco, Italy, 5Karolinska Hospital, Stockholm, Sweden, 6Wroclaw Medical University, Wroclaw, Poland, 7Hospital de la Princesa, Madrid, Spain, 8Klinikum der Goethe Universität, Frankfurt, Germany, 9Szent-Györgyi Medical University, Szeged, Hungary and 10Department of Virology, Cliniques St. Luc, Brussels, Belgium
Correspondence and offprint requests to: Professor Michel Jadoul, M.D., Cliniques Universitaires St Luc, Department of Nephrology, Université catholique de Louvain, Avenue Hippocrate 10, B-1200 Brussels, Belgium. Email: jadoul{at}nefr.ucl.ac.be
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Abstract |
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Methods. All chronic HD patients from 15 Belgian units were tested at (re)start of HD and every 18 months for anti-HCV antibodies (ELISA 2 in May 1991 and November 1992, then ELISA 3 until May 2000). All chronic HD patients from HD units from eight other European countries, whose prevalence of anti-HCV (+) patients had been studied in 19911994 (and published except in one country), were tested for anti-HCV antibodies in 1999.
Results. Anti-HCV (+) prevalence decreased (P<0.001) from 13.5 (1991) to 6.8% (2000) in the Belgian cohort (n = 1710). Prevalence also decreased (P<0.05) in the participating units from France (4230%), Sweden (169%) and Italy (2816%), tended to decrease in the participating units from UK (73%, P = 0.058) and Hungary (2615%, P = 0.057) but did not change (NS) in the participating units from Germany (7 to 6%), Spain (5 to 12%) and Poland (42 to 44%). In the Belgian cohort, the prevalence of anti-HCV(+) at (re)start of HD did not change significantly over 19912000.
Conclusion. The prevalence of anti-HCV(+) in HD has decreased markedly over the last decade in the participating units from most European countries. This decrease should reduce further the risk of nosocomial and occupational HCV infection in HD and ultimately contribute to improved long-term prognosis of HD patients and kidney graft recipients.
Keywords: epidemiology; haemodialysis; hepatitis C virus; prevalence, incidence
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Introduction |
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Subjects and methods |
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European study. In order to evaluate whether the trend observed in Belgium was also present in other European countries, we compared published anti-HCV(+) prevalence (19911994) with that observed in 1999.
Inclusion criteria were:
Study design
Belgian study. All patients on chronic HD in participating units were tested for anti-HCV(+) every 18 months from May 1991 until May 2000. The testing of patients at the time of (re)starting HD was not part of the design of our prospective study [2,3]. As anti-HCV antibodies virtually never wane in HD patients [2], all patients found anti-HCV() when first tested after 117 months HD were assumed to be negative at HD onset. In all patients found anti-HCV(+) when first tested, we investigated whether they were already anti-HCV(+) before or no later than within a month of HD onset. We were able to obtain this information in all anti-HCV(+) patients starting HD after September 1, 1991 (when ELISA 2 tests became widely available in Belgium) with the exception of two patients who were therefore excluded from this subgroup analysis. Prevalence at (re)start of HD was calculated accordingly.
European study. All national coordinators were sent a questionnaire concerning: (i) the type of virologic tests used for anti-HCV screening and confirmation in 1998 and 1999; (ii) the 1999 prevalence of confirmed anti-HCV(+) in their HD patients; (iii) the 19981999 incidence of seroconversion for HCV in the same population; (iv) the number of patients (re)starting dialysis in their unit(s) in 1998; (v) the prevalence of confirmed anti-HCV(+) in this 1998 cohort, and in particular in the subgroup restarting dialysis after a failed renal transplantation.
Prevention of HCV transmission relied exclusively on general hygienic precautions in the participating units from Belgium, France, Italy and Sweden. In contrast, anti-HCV(+) HD patients were isolated (either specific monitors or a separate ward) in Germany, Spain, Hungary, Poland and UK.
Virologic tests
In all nine countries, screening anti-HCV tests used in 1998 and 1999 were third generation ELISAs (Abbott, Chicago, IL or Ortho, Raritan, NJ).
Confirmatory testing relied on RIBA 3 (Ortho, Raritan, NJ) and/or western blotting (Innogenetics, Ghent, Belgium) and/or PCR (Roche, Branchburg, NJ) and/or repeat testing with another ELISA 3 (Ortho or Abbott).
Statistics
Standard statistical tests were performed. P values <0.05 were considered as significant.
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Results |
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Evolution of the prevalence of anti-HCV(+) patients and of the incidence of seroconversion for HCV. As shown in Figure 1, the prevalence of anti-HCV(+) patients dropped steadily from 13.5% in 1991 to 6.8% in 2000 (2 for trend, P<0.001). The incidence of seroconversion calculated between consecutive tests at 18 month intervals and expressed on a yearly basis, was 1.41 (19911992), 0.56 (19921994), 0 (19941995), 0.46 (19951997), 0.43 (19971998) and 0.63 (19982000), respectively.
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European multicentre study
Evolution of the prevalence of anti-HCV (+) patients: 19911994 vs 1999. As shown in Figure 2, the prevalence of anti-HCV(+) patients decreased significantly (2, P<0.05) in participating units from three countries (France, Italy, Sweden), tended to decrease in participating units from two others (UK, P = 0.058 and Hungary, P = 0.057) and did not change significantly in participating units from Germany, Spain and Poland.
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Prevalence of anti-HCV(+) patients (re)starting dialysis. The prevalence of anti-HCV(+) patients (re)starting dialysis in 1998 averaged 3.6% in Europe (21+/578), 15% (3+/20) in France, 0.4% (1+/234) in UK, 14.7% (5+/34) in Italy, 3.1% (3+/98) in Sweden, 4.4% (4+/90) in Poland, 7.5% (3+/40) in Spain, 4.6% (2+/43) in Germany, 0% (0+/19) in Hungary. The subgroup of patients restarting dialysis after a failed TP had a higher (2, P<0.03) prevalence (9.8%; 4+/41) than the rest of the cohort (3.2%; 17+/537).
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Discussion |
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The reduced prevalence observed in many countries has important implications. First, it decreases further the risk of HCV nosocomial transmission. As nosocomial infection currently accounts for most cases of hepatitis C transmission in HD [19], this will reduce further the prevalence of anti-HCV (+) in HD patients, with a beneficial snowball effect. The reduced prevalence might also improve the long-term survival of both HD patients and renal TP recipients (usually infected while on HD) [69]. Finally, the previously substantial risk of occupational exposure to HCV in HD units [20] should also decrease.
A reduction in the prevalence of anti-HCV(+) patients on HD has been mentioned [9] previously, on the basis of the 1992 and 1993 European Dialysis and Transplant Association (EDTA) registry data reporting prevalences of 21 and 17.7%, respectively [1,21]. The validity of the comparison between 1992 and 1993 is questionable. Indeed, the prevalence was calculated in units testing most or all HD patients for anti-HCV. In 1992, the proportion of such units was as low as 29% in UK or 48% in Finland. Taken together with the low and variable response rate to the EDTA registry in the early 1990s [1,21,22], this fact precludes any reliable comparison. Whatever the validity of the EDTA results, our data highlights that this claimed decrease is not uniform. Two large multicentre studies have also reported a decrease in anti-HCV prevalence in Spanish and Italian HD patients, respectively [11,23]. Unfortunately, the inclusion of many additional HD centres (+50%) during the Spanish study and the low (27%) response rate to the Italian survey limit the significance of the data. Outside Europe, the evolution of the prevalence of anti HCV(+) in HD patients remains poorly defined. The Centers for Diseases Control (CDC, Atlanta, GA) did not detect a significant trend (19921999) in the average prevalence of anti-HCV(+) (810%) in US HD centres [24]. Again, however, the prevalence was based on a variable number of centres testing for anti-HCV (rising from 22% in 1992 to 56% in 1999). The apparently stable US prevalence might in fact result from the association of an actual decrease in anti-HCV prevalence in centres participating from 1992, together with the subsequent recruitment of HD centres with a higher prevalence and/or the more recent use in the US of third generation tests. The long-term evolution of anti-HCV prevalence in other continents is completely unknown.
The falling prevalence is largely due to a lowered incidence of seroconversion in anti-HCV(+) patients on HD as the prevalence of anti-HCV(+) patients starting HD in Belgium was stable over 10 years. Contributing factors include the progressive reduction of blood transfusions due to the availability of erythropoietin in the late 1980s, followed in the early 1990s by the screening of blood donors with increasingly sensitive anti-HCV tests and the reinforcement of hygienic precautions, after seroconversions were detected in several units [24]. The treatment of anti-HCV(+) HD patients with interferon-alpha, available from the early 1990s, did not contribute significantly to the lower anti-HCV prevalence, at least in Belgium: fewer than five patients from the Belgian cohort received interferon-alpha. Finally, an impact on anti-HCV(+) prevalence, of a poorer survival of anti-HCV(+) than anti-HCV() patients cannot be excluded as a detailed, multivariate analysis of survival in our Belgian HD cohort is not available.
Despite the marked decrease of anti-HCV prevalence in European HD patients, the disappearance of HCV from HD units should not be expected for decades. As already stated, the prevalence of anti-HCV(+) in patients starting dialysis averages 3.6% in our European survey. A careful study of the Belgian cohort discloses for the first time that this prevalence did not change over the last decade. Interestingly the prevalence of anti-HCV(+) in patients restarting HD after a failed TP exceeds that observed in patients starting HD for the first time. This probably results from previous transfusions, nosocomial transmission and graft transmission [9].
The lower prevalence and seroconversion rate for HCV in HD, taken together with the stable prevalence in patients (re)starting HD (Figure 1) suggests that the fraction of anti-HCV(+) Belgian HD patients already infected before starting HD has risen over the last decade. Thus, the duration of HCV infection, a major determinant of the risk of cirrhosis and hepatocellular carcinoma [25], may be longer in Belgian anti-HCV(+) HD patients now than a decade ago, warranting a more aggressive pre-transplant evaluation and management.
Our study was not designed to study the effectiveness of different preventative policies. It is nevertheless noteworthy that the 19981999 incidence was no lower or higher in some units with isolation measures than in those relying on hygienic precautions without isolation. This finding probably reflects the shift of units with recurrent seroconversions towards an isolation policy, despite the disadvantages of this policy [26].
Several limitations of our study should be acknowledged. First, the polymerase chain reaction (PCR) was used as a confirmatory test in some anti-HCV(+) patients, but not performed systematically in all anti-HCV() patients. Thus, the actual prevalence of HCV infection may have been underestimated. Recent studies have however shown that PCR(+) but anti-HCV() HD patients are rarely detected when ELISA 3 is used [27]. In addition, the proportion of HCV infected HD patients missed by ELISA tests (window) is lower when the incidence of HCV infection is low, as currently observed in most units in our survey. Secondly, the confirmatory tests varied from country to country. This fact should not influence the observed trend within each country, the main finding of our study. Thirdly, the assessment of the evolution of prevalence was made more difficult by the consecutive use of ELISA 2 and 3 tests in several countries. Again, however, this may at most have artificially reduced rather than exaggerated the actual decrease in prevalence. Fourthly, whereas the Belgian study is prospective, the European survey is essentially retrospective, based on a convenience sample. This was based on strict criteria however, with 100% participation of the units invited to participate, all of which collected the 1999 data prospectively. Admittedly the study of even larger samples will be required to elucidate whether the detected trends are observed throughout Europe.
In conclusion, the prevalence of anti-HCV(+) in HD has decreased markedly over the last decade in participating units from most but not all European countries, a fact that should reduce further the risk of nosocomial and occupational HCV infection and contribute to an improved prognosis in ESRD patients.
Members of the HCV Collaborative Group
D. Becker, P. Bernis, B. Carlier, J. L. Christophe, A. Cuvelier, C. Cuvelier, R. Cuvelier, C. Fonck, J. Ghysen, E. Goffin, A. Hermant, J. Jamez, J. J. Lafontaine, H. Lalaoui, M. Lemaire, P. Leroy, G. Loute, J. M. Pochet, A. Quoidbach, F. Reginster, L. Stenuit, M. Wauthier, Departments of Nephrology, Université catholique de Louvain, Brussels, Belgium. J. L. Desassis, Centre Médical E. Rist, Paris, France. F. Fabrizi and M. Crepaldi, A. Manzoni Hospital, Lecco, Italy. M. Von Sydow, Karolinska Hospital, Stockholm, Sweden. M. Klinger and W. Weyde, Wroclaw Medical University, Wroclaw, Poland. E. Kiss and G. Gal, Szent-Györgyi Medical University, Szeged, Hungary.
Conflict of interest statement. None declared.
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References |
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