U.O. di Nefrologia e Dialisi, Servizio di Immunoematologia, e Trasfusionale, Azienda Ospedaliera, Fatebenefratelli e Oftalmico, Milano, Italy Email: dialisi.fbf.mi{at}katamail.com
Sir,
Hepatitis C virus (HCV) infection remains a significant public health concern in haemodialysis (HD) patients. Although generally asymptomatic, about 7085% of infections become chronic, and persistent infection may be associated with a wide spectrum of outcomes, ranging from mild non-progressive liver damage to severe chronic hepatitis, which progresses to cirrhosis, end-stage liver disease, and hepatocellular carcinoma.
Currently, it is still unclear how HD patients become infected. Nevertheless, both intradialysis (number of blood transfusions, duration and mode of dialysis, prevalence of HCV in the HD centres, breakdown of standard infection control practices) and extradialysis (high-risk lifestyle behaviour) variables have been identified.
Three diagnostic strategies are usually applied: (i) serial alanine aminotransferase (ALT) level testing (biochemical); (ii) screening enzyme-linked immunosorbent (ELISA-3) and supplemental strip immunoblot (SIA; RIBA-3) assay testing (serological); and (iii) an additional confirmatory test with polymerase chain reaction (PCR) (viral).
In 1998, the Centers for Disease Control and Prevention (CDC) recommended screening with serial ALT level testing, especially as serological-based tests may fail to identify 20% of infected individuals [1]. However, this biochemical-based strategy has several potential limitations for HD patients: (i) ALT levels are significantly lower than in non-uraemic subjects; (ii) ALT values in viraemic patients with histological disease may still fall within the normal reference range; (iii) non-specific sporadic ALT level elevations are common owing to co-morbidities and medications; and (iv) the positive predictive value of an elevated ALT level for de novo infections is less than 5% [2]. Because these limitations have cast doubt on this policy, the nephrology community had remained both undecided and divided: only 56% of dialysis centres in the United States tested their patients for HCV infection [3].
Recently, on April 27, 2001, the CDC released a new recommendation [4], stating that US Food and Drug Administration (FDA)-approved tests for diagnosis of previous or current HCV infection include those that measure anti-HCV and include ELISAs with a supplemental SIA (RIBA). Nevertheless, diagnosis of current (active) HCV infection can also be made by qualitative detection and by quantitative assay for HCV RNA. Even more recently, the FDA granted marketing approval for two HCV tests utilizing PCR technology: the Amplicor HCV test (version 2.0) and the Cobas Amplicor HCV test (version 2.0) [5]. These assays are designed to detect directly the qualitative presence of HCV RNA with a positive result indicating current infection. So far, quantitative assays for measuring the concentration of HCV RNA, less sensitive than qualitative PCR assays, are not FDA-approved.
In June 2001, anti-HCV(+) prevalence in our HD unit was 10.9% (seven out of 64 patients); we have had a progressive decrease since the early 1990s. Up to now, our HCV screening has been based on the following policy.
In our experience, there were significant correlations between screening/supplemental tests and confirmatory tests (HCV RNA): 21 out of 24 (87.5%) of our anti-HCV(+) patients were also found to be RNA(+). Moreover, none of our PCR(+) patients became negative, suggesting chronic infection.
In November 2000, in order to assess the presence of viraemia, we investigated our in-centre anti-HCV(-) chronic HD population for the presence of qualitative HCV RNA. Sixty-two anti-HCV(-) HD patients, all HBsAg(-) and anti-HIV(-) with normal serum ALT levels, including 37 males and 25 females, aged 3092 years (mean 65.5±15.5), with duration of dialysis 2146 months (mean 40.3±36.2), entered the study. None in this cohort was positive for serum HCV RNA, supporting the suggestion that HCV RNA tests are not needed as first line screening tests.
Our results additionally confirm that screening ELISA testing is a reliable predictor of HCV infection. Thus, supplemental tests are unnecessary and should be discontinued as they do not significantly add to screening assay specificity and are less informative but as expensive as detection of HCV RNA by PCR. Further, clearance of viraemia and recovery from HCV infection is extremely rare, indicating that regular testing for HCV should be limited to negative patients; positive patients should not need subsequent serological and virological testing. PCR is of value for the detection of current infection and for patients with liver disease who are PCR positive long before HCV serological tests become positive. Finally, we believe that testing for HCV is the only way to monitor the infection and provides the first and most important step in formulating practices and policies aiming at preventing the transmission of HCV within HD units.
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