Declared hepatitis C screening strategies in blood recipients in French hospitals.

AIMS OF THE STUDY: In spite of official recommendations and measures in France, screening strategies of hepatitis C performed in the field of transfusion are not clearly known. The aim of this study is to describe the screening strategies before and after the current year of the transfusion in blood recipients in several French medical departments and hospitals. MATERIALS AND METHODS: A qualitative study using the key informant technique was carried out. A sample of 179 departments and 64 hospitals in charge of patients transfused with low or high-volumes of homologous blood products was constituted. The key informants were asked about the number of homologous blood products, the number of recipients transfused in the hospital, the volume of transfusion performed, the existence of a single defined screening strategy, the time of prescription of the biological tests (before or after transfusion), the tests performed on cryopreserved blood samples, and the indications of the transfusion. RESULTS: The main screening strategy was HCV serology (second or third generation of enzyme immunoassays) with transaminase assessments before and after transfusion in 14% of the declared screening strategies. Screening tests were more frequently prescribed after transfusion, in at least 64% of the declared screening strategies according to the volume of transfusion. HCV serology was the common test prescribed in 61 and 50% of the screening strategies for low and high-volume transfusion respectively. The screening strategies showed a large heterogeneity combining HCV serology, transaminase assessment, before or after transfusion. CONCLUSION: A great heterogeneity of screening strategies was found. The most frequent was HCV serology with transaminase assessment before and after transfusion. Recommendations on screening strategies are needed in order to limit practice heterogeneity. This study will help building a cost-efficacy model in order to guide public health decision making.

The French haemophilia cohort: rationale and organization of a long-term national pharmacosurveillance system.

Medicinal products of biological origin still carry a specific iatrogenic risk, mainly because of their starting material, mode of preparation and variability. Careful postmarketing surveillance systems are therefore necessary. To assess the long-term safety of haemophilia treatment with plasma-derived and recombinant clotting factor products, a cohort study was set up in France in 1994. Participants were patients with haemophilia A and B, with or without previous clotting factor therapy. Clinical events, treatments, biological data and adverse events were recorded on standard forms. Blood samples were separated into serum, plasma and peripheral blood mononuclear cells, frozen, and banked in a central laboratory. The same data and samples were collected at yearly follow-up visits. As of December 1999, 1234 haemophiliacs were enrolled in 39 haemophilia centres. At enrollment, 50.2% of patients were under 15 years of age, and the cumulative number of days of exposure to the product was below 50 in 35.1% of cases. The median duration of follow-up was 26.9 months, with a total of 2729 patient-years (135,947 days of exposure and 211 million units of factor VIII or IX). To date, only 17 patients were lost to follow-up. The initial results show good compliance with this health-watch policy among patients and clinicians specializing in haemophilia. The regular follow-up data and centralized sample bank will serve to investigate rapidly any suspected outbreaks as soon as reliable biological tests become available in the future.

Cost-effectiveness of screening blood donors for hepatitis C and non-A, non-B, non-C hepatitis. The EATHIS Eco Research Group. European Acute Transfusion Hepatitis Interferon Study.

The current approach to screening for hepatitis C and non-A, non-B, non-C hepatitis in French blood transfusion centers involves a combination of a transaminase assay and tests for antibodies to hepatitis B core antigen (anti-HBc) and antibodies to hepatitis C virus (anti-HCV). A decision-analysis model was used to assess the cost-effectiveness ratio of this approach compared to the former approach, which included only transaminase and anti-HBc screening. Cost data were collected by a questionnaire sent to 26 centers throughout France. The average costs of diagnostic kits, equipment, staff, and administration were calculated. Estimates of prevalence and sensitivity values came from the medical literature. The cost-effectiveness ratio was expressed in French francs per infected donor detected. A sensitivity analysis of the variables in the model was performed to estimate the validity of the cost-effectiveness ratio. For 100,000 donations the incremental cost of the current approach reached FrF 2,566,111 (about US $500,000), with a marginal effectiveness of 180 donations detected. The sensitivity analysis showed the effect of prevalence on the incremental cost-effectiveness ratio. Transfusion centers may change their screening approach in areas of high or low prevalence of hepatitis C in France.

[Medical and economic evaluation of donated blood screening for hepatitis C and non-A, non-B, non-C hepatitis]. / Evaluation médico-économique du dépistage des hépatites C et non-A non-B non-C sur les dons de sang.

The aim of this study was to evaluate the cost of hepatitis C and non-A non-B non-C screening strategy in donated blood, currently used in French transfusion centres and to assess the effect in the blood transfusion centres according to the prevalence of the disease and the intrinsec values of tests. This screening strategy was based on alanine aminotransferase assay, and HBc and HCV antibodies detection. In 1993, a survey was conducted in 26 French transfusion centers to estimate the costs of the screening strategy currently used. Average expenditure on diagnostic sets, equipment, staff and administration charges for hepatitis C and non-A non-B non-C screening were calculated. From these results, we estimated the cost of the previous strategy which did not involve HCV antibody testing, so as to determine the incremental cost between the two strategies. We used clinical decision analysis and sensitivity analysis to estimate the incremental cost-effectiveness ratio with data gathered from the literature and examine the impact on blood transfusion centre. Implemented for 100,000 volunteer blood donations, the incremental cost of the new strategy was FF 2,566,111 (1992) and the marginal effectiveness was 180 additional infected donations detected. The sensitivity analysis showed the major influence of infection prevalence in donated blood on the incremental cost-effectiveness ratio: the lower the prevalence, the higher the cost-effectiveness ratio per contaminated blood product avoided.

[Transfusion and hepatitis C]. / Transfusion et hépatite C.

Hepatitis C has been a major transfusionnal risk until the beginning of the 90's, since it accounted for more than 90% of non-A, non-B hepatitis, 5% to 10% of infected surgical recipients and up to 50% of multitransfused patients, alltogether 100,000 to 400,000 blood components recipients in France. The decline in incidence was based principally on sequential introduction of donor testing, starting with surrogate markers in 1988 (transaminase ALT and antibody anti-core HBc), followed since 1990 by specific assays (anti-hepatitis C virus antibodies) and on blood donor selection. Two risk factors have been identified in donors, intravenous drug use and previous transfusion. The risk of transmission was estimated, after screening by first generation tests at 1 per 1670 units transfused. After second generation testing, the risk ranged from 1 in 2000 to 1 in 6000 units transfused, corresponding to a reduction of more than 90%. The estimation of the residual risk (mean: 1/100,000 donations in USA), principally due to incidence in regular donor required mathematical calculation. The new "hemovigilance" system in France with mandatory notification of all posttransfusionnal incidents and infections will contribute to evaluate and to prevent residual cases. However, further studies are necessary to precise other risk factors in donors, as well as the role of nosocomial infections in recent cases, and possibly the role of additional agents such as GB viruses in post-transfusionnal hepatitis.

Impact of screening donor blood for alanine aminotransferase and antibody to hepatitis B core antigen on the risk of hepatitis C virus transmission.

The transfusion-related risk of transmission of hepatitis C virus (HCV) was evaluated in France for the periods before and after exclusion of donor blood units with the surrogate markers elevated alanine aminotransferase (ALT) levels and antibody to hepatitis B core antigen (anti-HBc). A total of 1,412 blood recipients undergoing surgery were followed up prospectively in the period from 1986 to 1989. The stored serum samples were tested for antibodies to HCV by an enzyme immunoassay (EIA) and the result in reactive sera confirmed by a recombinant immunoblot assay (RIBA). The risk of HCV transmission was estimated by the maximum likelihood method for a subpopulation of 892 recipients divided into three groups. Of 55 (3.9%) EIA positive patients, 56.4% were found to be positive prior to transfusion. HCV seroconversion (positive RIBA) occurred in 22 patients (1.6%). The risk of HCV transmission per 1,000 transfused blood units decreased significantly from 4.11 in Group 1 (receiving non-screened blood) to 3.43 in Group II (receiving ALT screened blood) and to 1.40 in Group III (receiving ALT and anti-HBc screened blood). These results demonstrate that screening of donors for surrogate markers had reduced the risk of HCV transmission before the introduction of a systematic anti-HCV screening policy in France in March 1990.

Risk factors for hepatitis C virus infection in hepatitis C virus antibody ELISA-positive blood donors according to RIBA-2 status: a case-control survey.

Studies of blood donors positive for antibody to hepatitis C virus on enzyme-linked immunosorbent assay are probably biased by the large number of false-positive results. We evaluated the epidemiological and biological characteristics of 177 such donors with regard to the confirmatory second-generation RIBA test (Ortho Diagnostic Systems) and have compared the results to those from an age- and sex-matched control group of 177 donors negative for antibody to hepatitis C virus on enzyme-linked immunosorbent assay. Second-generation recombinant immunoblot assay was positive in 38% of cases, indeterminate in 6% and negative in 56%. The case-control study showed a significantly higher frequency of intravenous drug abuse (27% vs. 0%), blood transfusion (22% vs. 9%), history of jaundice (21% vs. 7%), elevated ALT level (49% vs. 4%) and HBc antibody positivity (32% vs. 7%) in second-generation recombinant immunoblot assay-positive donors. No such differences were found between the second-generation recombinant immunoblot assay-negative donors and their controls. The 35 second-generation recombinant immunoblot assay-positive donors without histories of transfusion or intravenous drug abuse had a significantly higher frequency of surgery with major blood loss or prolonged stays in areas of hepatitis B virus endemicity than did their controls (20% vs. 0% and 49% vs. 26%, respectively). In conclusion, at least one risk factor for HCV infection was identified in 82% of the second-generation recombinant immunoblot assay-positive donors, 91% of whom could have been identified on the basis of these risk factors, ALT level and presence of HBc antibody.

[Analytical study of the Abbott and Ortho tests for screening and confirmation of anti-HCV antibodies. Le groupe de Travail "Hépatites virales" de la Société Française de Transfusion Sanguine]. / Etude analytique des trousses de dépistage et de confirmation des anticorps anti-VHC Abbott et Ortho.Le groupe de Travail "Hépatites Virales" de la Société Française de Transfusion Sanguine.

Anti-HCV systematic screening on blood donation was mandatory in France since first of March 1991. Two laboratories (Ortho-Chiron and Abbott) have introduced in Europe successively two kinds of hepatitis C positive diagnosis with 1st and 2nd generation ELISA screening and confirmatory assays. The aim of this multicentric study was to evaluated the sensibility and specificity of these tests. For that, they used 10,090 blood sera. As a result we have seen that the new "second generation" screening assays have a higher sensitivity without less of specificity for the confirmatory tests.

[European Acute Transfusion Hepatitis Interferon Study (EATHIS)]. / European Acute Transfusion Hepatitis Interferon Study (EATHIS).

Since 1989, a prospective, multicentric and collaborative study, named European Acute Transfusion Hepatitis Interferon Study (EATHIS), involving 16 blood centres in France is coordinated by a task force in collaboration with the Viral Hepatitis and Recipients working groups of the French National Society of Blood Transfusion. A phase of recipient screening may be completed by a therapeutic interferon protocol. Among 1,476 transfused recipients receiving an average of 4.4 blood components, 1,011 were followed up at least four months. The incidence of non-A, non-B post-transfusion hepatitis (PTH) was varying from 0.1 to 6% at the different locations. Out of 15 hepatitis cases, 10 were diagnosed as post-transfusional. These preliminary data indicate a reduced incidence of PTH, with a mean of 1% for the period 1989-1991. It emphasises the importance of a transfusion vigilance program including follow up and testing for transaminases and specific viral markers.

[Hepatitis C virus and transfusion: policy regarding the donation and the donor. Groupe "Hépatites Virales" de la Société Nationale de Transfusion Sanguine]. / Virus de l'hépatite C et transfusion: attitude vis-à-vis du don et du donneur. Groupe "Hépatites Virales" de la Société Nationale de Transfusion Sanguine.

Hepatitis C virus (HCV) discovery and introduction of anti-HCV antibodies screening in blood transfusion imply the necessity of a good blood donations and blood donors policy. Detection of a seropositivity during the screening must be completed with a confirmatory test. The results are directly used to inform donors and define the blood products policy. Donors with positive results on confirmatory test are discarded and have physical and biological examinations in hepatology. Individuals with indeterminate or negative results must be retested for the HCV serology. Furthermore, because of a rapid improvement in the fields of technology, diagnosis and therapy of HCV, an adaptation of the policy is necessary.

Transmission of HIV by transfusion of HIV-screened blood: the value of a national register. The 'Recipients' Study Group of the French Society of Blood Transfusion.

A National Register of transfusion-transmitted infections was opened by the French Society of Blood Transfusion on 1 October, 1986. Out of 54 initially reported cases of HIV-infection, allegedly transmitted by blood components, further investigation could be completed in 33 cases. The transfusional origin of contamination was considered as established or probable in 28/33 cases, either because a potentially infectious unit was identified among those transfused to the recipient (23/28), or because the recipient was known to be seronegative before transfusion (5/28), or both (10/28). In 5/33 cases transfusion was considered as presumably responsible for contamination because no other risk factor was found in the recipient. Among the 33 documented cases of HIV-transmission by screened blood, 29 (88%) occurred between 1985 and 1987, and four (12%) during 1988. Out of 19 implicated donors later found seropositive, 16 belonged to a high-risk group for HIV-infection. The majority of HIV-infections occurred as a consequence of blood donation in the window period between contamination and the appearance of detectable antibodies in the donor's serum (11/19). In three instances, however, human and operational errors led to the release of seropositive units. We conclude that the main value of this Register is to provide a potential trend-indicator of transfusion-related infectious risks, to allow objective documentation of reported cases and to contribute to the improvement of blood transfusion practice.

Transmission of serologically silent hepatitis B virus along with hepatitis C virus in two cases of posttransfusion hepatitis.

The polymerase chain reaction (PCR) was used to investigate the presence of hepatitis B virus (HBV)-related DNA sequences in blood from three blood donors and two transfusion recipients who developed posttransfusion non-A, non-B hepatitis (NANBH). In the first case, the sole donor was positive for antibody to hepatitis B surface (HBs) and core (HBc) antigens and had elevated alanine aminotransferase (ALT) levels, while the recipient had no HBV serologic markers. Both the donor and the recipient had serologic markers of hepatitis C virus (HCV) and were found positive for HBV DNA and HCV RNA sequences by PCR. The second case involved two donors and one recipient. Serologic tests for conventional HBV markers were negative in all three individuals, but one of the donors had elevated ALT. HBV DNA sequences were detected by PCR in the serum of the recipient and of the donor with high ALT, but not in the serum of the donor with normal ALT. Anti-HCV was detected in the serum of the recipient and of the suspect donor but not in that of the donor with normal ALT. The sequences amplified in the S region and determined after cloning of PCR products for both donor-recipient pairs were indistinguishable from each other and identical to the sequence of the major HBV subtype of adw in the first case and ayw in the second case. Furthermore, for the second case, an identical single-point mutation was found in both the donor and the recipient. These data confirm the transmission of conserved HBV sequences together with HCV in posttransfusion NANBH.(ABSTRACT TRUNCATED AT 250 WORDS)

[Practical approach to the discovery of serum markers for infection by hepatitis B virus (HBs antigen or anti HBc antibody). Hypertransaminasemia or the two anomalies in a blood donor]. / Attitude pratique devant la découverte de marqueurs sériques d'infection par le virus de l'hépatite B (antigène HBs et/ou anticorps anti-HBc). Une hypertransaminasémie ou les deux anomalies chez un donneur de sang.

By now in France HBV seric markers (Ag HBs and Ac HBc) and transaminases level (ALT) screenings are compulsory by law in blood donors. People whose blood donation is discarded should be informed. A clinical, epidemiological and virological survey of such donors is required to differentiate healthy Ag HBs carriers and patients suffering from hepatitis B (who may eventually be treated). Similar guidelines may be recommended for the blood donors presenting high transaminases level without HBV seric markers in order to find a cause for such impaired biochemical tests: overweight, alcohol, drug consumption, auto-immune liver disease, genetic disorder, Non-A, Non-B, Non-C hepatitis....