Liver dysfunction in allogeneic bone marrow transplantation recipients.

Liver dysfunction is common in allogeneic bone marrow graft recipients, but no systematic studies of pre- and posttransplantation liver biopsies have been performed to identify and compare hepatic lesions. This study involved 25 consecutive patients who had undergone serial viral screening tests, liver tests, and pre- and posttransplantation liver biopsy. The aims were to ascertain the origin of liver disorders prior to bone marrow transplantation, to determine the mechanism and severity of liver dysfunction occurring early after transplantation, and to identify a possible relationship between pre-existing liver lesions and the frequency and nature of early liver dysfunction after transplantation. Pretransplantation biochemical liver tests were abnormal in 72% of patients, despite the absence of clinical liver disease. Eleven patients had chronic viral hepatitis B or C. Mild or moderate histological lesions were present in all the patients, with bile duct abnormalities in 48%, central vein abnormalities in 24%, sinusoidal fibrosis in 52%, portal fibrosis in 88%, portal necrosis in 52%, and parenchymal siderosis in 76%. After transplantation, fatal veno-occlusive disease occurred in two patients and biochemical abnormalities occurred in 24. Coded review of needle biopsy specimens failed to provide a single diagnosis. Histological lesions differed between pre- and posttransplantation biopsy specimens only by increased iron overload (96%, P<0.01). We conclude that pretransplant liver lesions contribute to hepatic dysfunction early after bone marrow transplantation, being very similar in nature and degree to lesions observed posttransplantation.

Screening blood donations for hepatitis C in Central Africa: analysis of a risk- and cost-based decision tree.

Four screening strategies (no testing, HC Abbott, HC Pasteur, and a combined test) for the detection of hepatitis C virus (HCV) antibody in donated blood were considered in a formal decision tree. Decision criteria included residual risk of infection and overall monetary cost. Tree parameters were determined using data from the Central African Republic. The prevalences observed among blood donors for HIV infection, hepatitis B, syphilis, and hepatitis C varied between 6% and 15%. The current residual risk of transfusion-transmitted infections is very high (8.4%). Screening for HCV would bring that risk down to about 3% with either the HC Pasteur, the HC Abbott, or the combined test. Even though baseline analysis gives preference to the HC Abbott test (the combined test coming out last), Monte Carlo sensitivity and uncertainty analyses showed that Abbott's and Pasteur's tests are interchangeable, on the basis or either risk or cost considerations.

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.

[Systematic peroperative use of an autotransfusion system in heart surgery. A prospective and comparative study in 283 patients]. / Utilisation peropératoire systématique d'un système d'autotransfusion en chirurgie cardiaque. Etude prospective et comparative sur 283 malades.

A series of 283 patients undergoing cardiac bypass surgery was studied to determine whether intraoperative autotransfusion, haemodilution, and a change in transfusion techniques of the same surgical team could reduce homologous blood requirements. The Cell-Save Haemonetics* system was used systematically in 167 consecutive patients (Group I). This group of autotransfused patients was analysed prospectively and compared with a control group (Group II) of 116 patients operated one year before and analysed retrospectively. During the whole hospitalisation, homologous blood products were required in 40.7% of patients in Group I compared with 73.3% of patients in Group II (p less than 0.0001). The average requirements of packed cells per patient were 2.7 +/- 1.3 in Group I compared with 4.1 +/- 2.5 in Group II (p less than 0.0001). The haematocrit on discharge from the department was 29.9 +/- 4% in Group I compared with 32 +/- 4.5% in Group II (p less than 0.0001). The average volume of blood recovered by the system and then autotransfused was 620.8 +/- 242.6 ml. There was no significant difference in postoperative bleeding in the first 24 hours between the two groups. This study confirms that peroperative autotransfusion during cardiac surgery and the acceptance of a clinically well tolerated normovolumic anaemia are associated with a significant reduction in homologous blood consumption.

[Transfusional strategy in neurosurgery: preoperative hemodilution by erythrocytapheresis]. / Une stratégie transfusionnelle en neurochirurgie: hémodilution préopératoire par érythrocytaphérèse.

Autologous blood transfusion techniques have been devised in order to decrease the risk of homologous transfusion-related complications. In neurosurgery, preoperative autologous blood collection is difficult because of the rather short time interval before surgery, as well as the risk of increasing cerebral oedema or intracranial hypertension. Therefore erythrocytapheresis has been performed the day before surgery as a preoperative haemodilution in 33 patients, using a discontinuous flow cell separator (PCS + Heamonetics). Patients with anaemia, unstable cardiovascular condition, infections, malignant tumor with a bad prognosis, or a poor peripheral venous status were not included. The mean volume of collected red cells was 526 +/- 176 mL, allowing a minimal colloid perfusion adjusted on this volume, with a simultaneous restitution of plasma and platelets. For a mean peroperative estimated blood loss of 1,040 +/- 52 mL, a homologous blood transfusion was avoided in 29 patients (88%). Four patients who underwent meningioma surgery received homologous red cells units in addition to their autologous blood. Two patients did not require any transfusion. Finally, 88% of autologous red cells units were readministered and 8 units were not retransfused. Preoperative erythrocytapheresis has proven to be a very simple and well tolerated technique. It can be considered for elective neurosurgery, when the time delay before surgery is short and when the blood loss is anticipated as to be moderate. It may also be associated with iterative autologous blood donation programme or the peroperative use of a cell saver.

Ultraviolet irradiation of platelet concentrates: feasibility in transfusion practice.

Ultraviolet (UV)-B irradiation abolishes lymphocyte functions (the ability to respond and to stimulate) in mixed lymphocyte culture (MLC). This effect may have practical application in the prevention or reduction of transfusion-induced alloimmunization against HLA class I antigens. To study this, platelet concentrates (PCs) were obtained with a cell separator, suspended in autologous plasma in a final volume of 400 mL, and transferred into a large (22 X 30 cm) cell culture bag. This plastic showed a good transmittance of UV-B rays at 310 nm (54%). PCs were placed between two quartz plates (surface of irradiation = 25 X 37 cm), and the two sides were irradiated simultaneously. Energy delivered to the surface of the plastic bag was automatically monitored. The ability to respond (in MLC and to phytohemagglutinin) and to stimulate allogeneic lymphocytes was completely abolished with energy of 0.75 J per cm2 (irradiation time less than 3 min). The temperature increase during irradiation was negligible. Platelet aggregation (collagen, adrenalin, ADP, arachidonic acid, ristocetin) was not impaired if UV-B energy was below 3 J per cm2. Recovery and survival of autologous 111In-labeled platelets were studied in four volunteers; no differences were found between UV-B-treated (1.5 J/cm2) platelets and untreated platelets. These results show that a large-scale clinical trial using UV-B-irradiated PCs to prevent HLA alloimmunization is feasible.

[Investigation of a transfusion contaminated by HTLV-I virus]. / Enquête à propos d'une contamination transfusionnelle par le virus HTLV-I.

In front of the successive development of an HTLV-I seroconversion and a neuromyelopathy in a French Caucasian following a cardiac transplantation, an ascendant epidemiologic investigation must be manage to search a risk factor or a possible blood donor contaminated with HTLV-I virus. We selected an HTLV-I seropositive donor whose RBC participated to the patient's transfusion. This woman from Martinique island was a regular donor in our blood center and a second investigation was initiated to examine the patients transfused with the blood products issued from her previous donation. Nine were identified and controlled among them a patient who has received a RBC was found HTLV-I seropositive. An evaluation of the infectivity of the different blood products according to their type and specificity has been done. These data confirm that transmission of the HTLV-I is possible through donation of healthy seropositive donor and can induce the development of associated pathology, and prove the importance of screening blood donors for HTLV-I antibodies.

Post-transfusional anti-HCV-negative, non-A, non-B hepatitis. (I) a prospective clinical and epidemiological survey.

Despite the identification of hepatitis C virus (HCV) and the detection of anti-HCV antibodies in the serum of infected individuals, a sizeable proportion of patients who develop transfusion-associated acute non-A, non-B hepatitis following surgery do not develop anti-HCV antibodies. The cause of this disease remains unknown. To assess the role of homologous blood transfusion in anti-HCV-positive and -negative, non-A, non-B hepatitis following surgery, patients receiving homologous blood, autologous blood alone, or no transfusions were prospectively studied. Consumption of potentially hepatotoxic drugs was also quantified. Anti-HCV antibodies were tested retrospectively when commercial assays became available. Of the 181 patients who received homologous blood which tested negative for surrogate markers of infectivity, 19 (10.5%) developed non-A, non-B hepatitis, associated with anti-HCV seroconversion in three cases. Of the 90 autologous blood recipients, non-A, non-B hepatitis developed in one (1.1%), who did not seroconvert to anti-HCV. Of the 64 untransfused patients, non-A, non-B hepatitis developed in one (1.6%), who was anti-HCV-positive before surgery. Logistic regression analysis showed that the occurrence of non-A, non-B hepatitis was associated with homologous blood transfusion, but not with the consumption of potentially hepatotoxic drugs. The 16 homologous-blood recipients who developed anti-HCV-negative, non-A, non-B hepatitis had received blood from 70 donors, none of whom had detectable anti-HCV antibodies but six of whom had minimal elevations of serum aminotransferase activity. Anti-HCV-negative, non-A, non-B hepatitis is mainly transfusion-transmitted in the surgical setting. Known hepatotropic agents may be involved despite the absence of usual serum markers, but our results are also consistent with the involvement of an unidentified non-A, non-B, non-C agent.

Human immunodeficiency virus-specific cytotoxic responses of seropositive individuals: distinct types of effector cells mediate killing of targets expressing gag and env proteins.

By using target cells that expressed isolated env, gag, p27nef, or p23vif molecules introduced by recombinant vaccinia viruses containing genes encoding these polypeptides, it was possible to identify env, gag, p27nef, and p23vif as cytolytic target antigens for freshly isolated blood cells from human immunodeficiency virus 1 (HIV-1) seropositive patients. Most of the patients tested (95%) manifested a specific cytotoxic activity against vaccinia virus-env-infected target cells. The env-specific cytotoxic activity was not restricted by the major histocompatibility complex and was not mediated by T lymphocytes, as shown by the absence of blocking effect with an anti-CD3 monoclonal antibody and by the inefficiency of CD3+, CD8+, or CD4+ and CD8+ depletion to reduce the cytotoxic activity against the env-expressing target cells. In the same conditions, the cytotoxic activity specific for gag was abrogated and gag major histocompatibility complex-restricted cytotoxic T lymphocytes were detected in 85% of the subjects tested. Therefore, in a HIV-1 seropositive subject, distinct types of effector cells mediate the lysis of target cells expressing gag and env proteins.

A multicenter evaluation of the routine use of a new white cell-reduction apheresis system for collection of platelets.

BACKGROUND: Residual white cells (WBCs) cause serious side effects in platelet transfusion. An in-line WBC-reduction system based on fluidized particle bed technology was recently developed as a modification of an existing plateletpheresis system. STUDY DESIGN AND METHODS: In an investigational phase, three flow profiles were evaluated using prototype software in five centers, each using their standard conditions. In the confirmatory phase, the released software was tested in three centers. WBCs were counted in two full Nageotte grids (dilution 1-in-5). RESULTS: With the prototype software, WBC levels were always below 1 x 10(6) per procedure (median, 25,000/procedure; n = 314). One profile proved to be superior to the other two with respect to platelet yield and residual WBCs, and it was incorporated in the released WBC-reduction system, together with a built-in process control. Median residual WBCs in these WBC-reduction system components not rejected by the process control were 19,000 per procedure (n = 211/225 total), with 99.5 percent of the platelet components having less than 1 x 10(6) WBCs. CONCLUSION: The protocol selected in the initial phase, now available as a WBC-reduction system, results in platelet concentrates with very low residual WBC levels. This satisfies even the most stringent criteria for WBC reduction in platelets, without the platelet loss typically seen with conventional fiber filtration.

HCV infection in a rural population of the Central African Republic (CAR): evidence for three additional subtypes of genotype 4.

The prevalence of hepatitis C virus (HCV) antibodies, HCV infection, and genotypes was studied in a rural population of the Central African Republic. In five villages, blood samples were taken from all the inhabitants present during the survey, belonging to Pygmies (299) and to Bantu and Banda ethnic groups (247). Using a second-generation ELISA screening and confirmation by immunoblot assay for the detection of HCV antibodies, all the Pygmies were negative, whereas seven Bantus/Bandas, aged > 35 years and with no familial relationship, were positive, giving a prevalence of 2.8% in this ethnic group. Five samples were also PCR positive; all belonged to genotype 4, but with three new subtypes identified by phylogenic analysis. These results indicate the co-existence of different HCV subtypes and raise questions about the natural transmission of HCV in this secluded population.

Hepatitis C virus (HCV) genotype analysis in apparently healthy anti-HCV-positive Parisian blood donors.

BACKGROUND: As only a few studies have examined the prevalence of various hepatitis C virus (HCV) subtypes in blood donors, information about the variability and route of infection in apparently healthy persons is limited. STUDY DESIGN AND METHODS: Blood donations collected at a large Parisian hospital (52,441) were investigated for antibodies to HCV. Serum samples were screened with an enzyme immunoassay. All HCV-positive donations were retested with a second enzyme immunoassay and confirmed by immunoblot. The HCV genotype was determined for all polymerase chain reaction-positive subjects. Untypable genotypes were sequenced in the NS5B region. RESULTS: In total, 83 (0.26%) blood donors were anti-HCV positive. Men (0.34%) were significantly more likely to be infected (p < 0.001) than women (0.19%). Prevalence rates in men between 20 and 39 years of age were higher than those in similar women (p = 0.01), but greater in women aged from 50 to 65 years (p = 0.05). Fifty-five sera were viremic, of which 49 could be genotyped by a line probe assay. One new HCV type 1 subtype and three new HCV type 2 subtypes were discovered. In total, 28, 10, 11, 5, and 1 serum samples were grouped into HCV types 1 through 5, respectively, involving a total of 13 subtypes. The mean age of HCV type 2-infected donors was 42 +/- 11 years, but that for type 3-infected subjects was only 30 +/- 4 years (p = 0.0048). Forty-nine subjects showed elevated alanine aminotransferase levels; 39 (80%) of these subjects were viremic (p < 0.05). CONCLUSION: Among the sampled population, an HCV prevalence rate of 0.26 percent was found, with the five most common European genotypes causing the infections. Four new subtypes were discovered. Correlation between genotype and risk factors was not apparent, but links with age, sex, and ethnic origin emerged.

Evidence for high genetic diversity and long-term endemicity of hepatitis C virus genotypes 1 and 2 in West Africa.

During 1994 and 1995, the prevalence of hepatitis C virus (HCV) and its genotypes were studied in several rural and urban populations in three West African countries: Guinea, Burkina Faso, and Benin. The following groups were screened for antibodies to HCV (anti-HCV): 459 villagers in the forest region of Guinea; 965 individuals in urban, suburban, and rural populations of the Bobo Dioulasso area, Burkina Faso; and 582 blood donors in Cotonou, Benin. In Benin, 60 patients with sickle cell anemia (30 with and 30 without history of multiple transfusion) and 13 hospital patients with liver disease were also tested. RT-PCR detection of HCV-RNA was carried out on all anti-HCV positive samples, followed by genotyping and sequencing of unrecognized subtypes. The prevalence rates of anti-HCV were 1.1% in the Guinean population group, 1.4% among blood donors in Benin, and 4.9% in residents of Burkina Faso. In patients with sickle cell anemia, five of the 30 polytranfused patients (17%) had anti-HCV, whereas none of the patients without a history of blood transfusion had anti-HCV (P < 0.05). Among the 13 patients with liver disease, five had anti-HCV, of whom four had history of blood transfusion. HCV-RNA was detected in 41 anti-HCV positive sera. All belonged to genotypes 1 or 2, with a high genomic diversity; 18 different subtypes were identified, including 2c, 2d, and 16 new subtypes. Such genetic diversity poses a challenge for vaccine development and also implies that HCV infection is long-established in these West African regions.