Costs and cost-effectiveness of different follow-up schedules for detection of occupational hepatitis C virus infection.

OBJECTIVE: The purpose of this study was to compare the costs and cost-effectiveness (C/E) of early hepatitis C virus (HCV) RNA testing (alternative-US recommendations) after occupational exposure to HCV with existing follow-up strategies: (1) French, anti-HCV antibodies and alanine transaminase (ALT) activity at months 1, 3 and 6; (2) European, monthly ALT activity for 4 months and anti-HCV antibodies at month 6; (3) and baseline-US, anti-HCV antibodies and ALT activity at month 6. METHODS: A decision tree simulated each strategy for 7300 healthcare workers (HCWs) exposed to HCV each year in France, taking into account the impact of early diagnosis on the response to antiviral treatment and the deterioration of HCW quality of life after exposure. RESULTS: For a HCV transmission risk of 0.5% after exposure, the French strategy led to the highest costs/person (181.40 euros) and the baseline-US strategy to the lowest (126.60 euros) (178.50 euros) for alternative-US). The shortest mean time to HCV infection diagnosis (1 month) and the lowest number of chronic hepatitis C (CHC) patients (1.9/7300 HCWs exposed) was obtained with the alternative-US strategy (vs 6 months and 7.9 CHC, respectively with baseline-US). Compared with the alternative-US, the French strategy was associated with higher costs and lower utilities, and the European with a higher incremental C/E ratio. Compared with the baseline-US strategy, the alternative-US strategy C/E ratio was 2020 euros per quality-adjusted life year saved. CONCLUSION: In HCWs exposed to HCV, a strategy based on early HCV RNA testing shortens the period during which the HCW's wait for his HCV status, leads to lower risk of progression to CHC and is reasonably cost-effective.

High prevalence of hepatitis C virus infection and predominance of genotype 4 in rural Gabon.

Hepatitis C (HCV) molecular epidemiology is documented poorly in central African countries. In response to this, a population-based study of 319 consenting adults resident in a remote village of Gabon was undertaken (mean age: 38 years; age range: 13-85+; sex ratio: 0.74). Screening for anti-HCV antibodies was performed using ELISA and recombinant immunoblot assay. Seropositive samples were assessed further with viral load and genotyping techniques. Sixty-six (20.7%) individuals were HCV seropositive. Viral loads ranged from 600 to 24.9 million IU/ml (median: 372,500). Seroprevalence and viral loads increased significantly with age (P < 10(-5) and P < 0.003, respectively). HCV sequences of the 5'UTR genome region were obtained from 60 (90.9%) samples and NS5B region sequences were obtained from 22 (36.6%) samples. All strains belonged to subtypes of genotype 4: 4e (72.7%), 4c (13.6%), 4p (4.5%), 4r (4.5%) and one unclassified genotype 4 strain. Evolutionary analysis of the subtype 4e sequences indicates a period of raised transmission during the early twentieth century.

Changing of hepatitis C virus genotype patterns in France at the beginning of the third millenium: The GEMHEP GenoCII Study.

This cross-sectional study aimed to investigate, during a short period between 2000 and 2001, in a large population of patients with chronic hepatitis C, the epidemiological characteristics of hepatitis C virus (HCV) genotypes in France. Data from 26 referral centres, corresponding to 1769 patients with chronic hepatitis C were collected consecutively during a 6-month period. HCV genotyping in the 5'-non-coding region (NCR) was performed in each center using the line probe assay (LiPA, in 63% of cases), sequencing (25%) or primer-specific polymerase chain reaction (PCR) (12%). HCV genotypes 1a, 1b, 2, 3, 4, 5, non-subtyped 1 and mixed infection were found in 18, 27, 9, 21, 9, 3, 11 and 1% of our population, respectively. HCV genotype distribution was associated with gender, age, source and duration of infection, alanine aminotransferase (ALT) levels, cirrhosis, alcohol consumption, hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection. In multivariate analysis, only the source of infection was the independent factor significantly associated with genotype (P = 0.0001). In conclusion, this study shows a changing pattern of HCV genotypes in France, with i.v. drug abuse as the major risk factor, an increase of genotype 4, and to a lesser extent 1a and 5, and a decrease of genotypes 1b and 2. The modification of the HCV genotype pattern in France in the next 10 years may require new therapeutic strategies, and further survey studies.

Hepatitis C virus detection in follicular fluid and culture media from HCV+ women, and viral risk during IVF procedures.

BACKGROUND: Hepatitis C virus (HCV) has been detected in sperm, but no data are available on follicular fluid (FF) collected on IVF procedures. The aim of this study was to: (i) search for HCV RNA in FF and in culture media at each step of IVF undergone by HCV(+) women; (ii) investigate the impact of blood contamination of FF induced by vascular injury associated with transvaginal ovarian puncture; (iii) assess risk for the embryo and the impact on the contamination rate of the newborn; and (iv) determine the viral risk presented by these fluids in order to define guidelines for the laboratory. METHODS: FF from 22 IVF procedures performed in 17 HCV(+) women were classified as either clear, lightly bloody or bloody FF. Oocytes from each FF were washed and incubated in separated fertilization media. At 20 h after puncture (day 1), the fertilized oocytes were washed and transferred to fresh media until embryo transfer. HCV RNA was detected and quantified in FF and media using Cobas Amplicor and Cobas Monitor HCV RNA kits. RESULTS: HCV RNA was positive in 39 of 44 FF samples, and viral loads increased with blood contamination. At day 1, after rinsing of oocyte-cumulus complexes, only 8 of 44 media were still positive. Viral loads were quantified in 5 of 8 positive media, were below the test sensitivity threshold in 4 of 5 HCV RNA-positive media, and just above it in the fifth medium. The day of transfer HCV RNA was undetectable in all media. CONCLUSIONS: HCV RNA was detected in 89% of FF irrespective of the degree of blood contamination, and in 25% of the media at day 1. FF must be considered as potentially infected. Blood contamination increases HCV load in the FF. Rinsing oocytes seems significantly to discard the HCV RNA. It is too early to assess the impact of IVF on the contamination rate of HCV mothers' offspring. After counselling, attempting IVF in HCV(+) women is justified. Universal guidelines prevent nosocomial infection, and IVF does not specifically increase the professional risk.

Effects of hepatitis C virus on the apoptosis percentage of granulosa cells in vivo in women undergoing IVF: preliminary results.

BACKGROUND: The aim of this study was to investigate the relationship between the apoptosis percentage of human luteinized granulosa cells (GC) and the presence of hepatitis C virus (HCV) in follicular fluid (FF). METHODS: GC were isolated from FF of 12 women undergoing 12 IVF cycles: six were HCV+ with active viral replication and six HCV- serving as controls. No male partner was HCV+. HCV detection and quantification were assessed by reverse transcriptase-polymerase chain reaction in serum, FF and embryo-incubation medium. GC were analysed by flow cytometry after propidium iodide staining to measure the percentages of apoptotic GC. Routine IVF parameters were tabulated. RESULTS: Mean +/- standard deviation (SD) serum and FF HCV viral loads were 3.58 +/- 4.25 x 10(6) and 0.14 +/- 0.10 x 10(6) IU/ml respectively. Mean percentages of apoptotic GC from HCV+ and HCV- women were 3.08 +/- 1.14 and 3.14 +/- 1.40% respectively. No statistically significant difference was found between these two groups concerning GC apoptosis and when we compared all IVF parameters. No HCV RNA was detected in embryo incubation media after 2 days of culture. CONCLUSIONS: Comparing GC apoptosis percentages and usual IVF parameters in the HCV+ group versus the HCV- group, our preliminary study shows that active chronic HCV infection does not affect follicle development and IVF outcome in HCV+ women undergoing IVF. Furthermore, the risk of newborns becoming HCV-infected might not be increased by assisted reproductive technologies when performed in couples in which women are HCV+ and men HCV-.

[Evaluation of three testing strategies for detection of hepatitis C in a hospital medical consultation and in an HIV testing center]. / Evaluation de trois stratégies de dépistage de l'hépatite C en consultation hospitalière de Médecine générale et dans un Centre de dépistage anonyme et gratuit du virus de l'immunodéficience humaine.

AIMS: Testing for hepatitis C virus (HCV) is recommended. The purpose of this study was to evaluate the efficacy of HCV testing in a medical consultation without an appointment and in an HIV testing center based on three testing strategies: 1997 French Consensus Conference, "Lettre de la Direction Générale de la Santé" (January 1996), and extension to other risk factors. PATIENTS AND METHODS: For 6 months a free blood test was offered to any patient with a risk factor according to the literature. RESULTS: There were 1 736 new patients at the medical consultation and 1 616 at the testing center. The patients were younger at the testing center than at the medical consultation (31.1 vs 43.3 years; P<0.001). Acceptance of screening was better at the testing center (97.8% vs 75.2%; P<0.001). There were more patients exposed to one of the risk factors at the testing center (31.2% vs 13.9%; P<0.001). Tests were more efficient at the testing center: 30 HCV positive patients/1 616 (1.86%) vs 11/1 736 (0.63%, P<0.01). Tests based on the 1997 French Consensus Conference provided detection in 27/30 (90%) of HCV positive patients at the testing center but only 4/11 (36.3%) at the medical consultation (P<0.01). CONCLUSION: Testing was effective in both places but was more efficient at the testing center. Efficacy of the testing strategies differs significantly according to the place of screening. At the testing center, screening can be restricted to patients with a history of intravenous drug use and blood transfusion. At the medical consultation, screening should be extended to other risk factors.

Autologous platelet concentrate as an adjunct in macular hole healing: a pilot study.

PURPOSE: A pilot study was undertaken to assess the efficacy of autologous platelets in macular hole healing. PATIENTS AND METHODS: Eight eyes of eight patients with stage 3 or 4 macular holes, two of which had failed to heal after previous vitrectomy and gas tamponade, were included. The procedure consisted of pars plana vitrectomy with removal of posterior cortical vitreous, stripping of associated epimacular membranes, 15% perfluoroethane-air tamponade, and instillation of autologous platelet concentrate onto the posterior pole. Strict postoperative facedown positioning was observed for 12 days. Postoperative evaluation included visual acuity measurement, biomicroscopic macular appearance and scanning laser ophthalmoscope examination. The follow-up period ranged from 3 to 13 months (mean, 7 months). RESULTS: Of eight eyes, flattening of the surrounding retina and closure of the hole were achieved in seven (87.5%). Visual acuity improved two lines or more in four eyes (50%) Four eyes (50%) reached a postoperative visual acuity of 20/50 or more. Increased nuclear sclerosis was observed in six eyes (75%), and retinal detachment occurred in two eyes (25%). CONCLUSIONS: Autologous platelet concentrate administered peroperatively in full-thickness macular holes seems to be a safe and effective adjunct to vitrectomy with removal of posterior hyaloid and gas tamponade. A larger multicenter randomized prospective study is underway to verify these encouraging results before advocating the use of autologous platelets in macular hole surgery.

Hepatitis C virus genotypes in French blood donors.

The prevalence of different hepatitis C virus (HCV) genotypes in HCV infected individuals and the relation between the HCV genotypes and the source of the infection are controversial. The aim of this study was to determine the HCV genotypes in French blood donors. Fifty-one anti-HCV positive blood donors were studied with detectable serum HCV RNA by nested polymerase chain reaction (PCR) using primers derived from the 5' non-coding region. For genotyping HCV, we used a method based on analysis of the restriction fragment length polymorphisms (RFLP) after amplification by PCR of the HCV non-structural 5 (NS5) genome domain. Using this technique, the genotypes of 39 of the 51 blood donors (76%) were determined. Three previously described genotypes were found: 19 blood donors were infected by HCV genotype I (37%), 14 were infected by HCV genotype II (27%), 3 were infected by HCV genotype III (6%), and 3 were coinfected by two genotypes (6%). All three blood donors infected with two different genotypes were intravenous drug abusers. A past history of intravenous drug abuse was more frequent in blood donors with HCV genotype I. However, there was no difference in alanine transaminase (ALT) levels, histological lesions, and RIBA-2 patterns in blood donors infected with either HCV genotype I or HCV genotype II. These findings indicate that most HCV genotypes isolated from French blood donors belong to HCV genotype I and HCV genotype II, and that risk factors for HCV infection may differ for different genotypes of HCV.

Hepatitis C virus (HCV) viremia in human immunodeficiency virus-seronegative and -seropositive patients with indeterminate HCV recombinant immunoblot assay.

Positivity of recombinant immunoblot assay (RIBA) for detection of antibodies to hepatitis C virus (anti-HCV) is usually associated with HCV viremia. The significance of an indeterminate RIBA result, defined by reactivity to only one HCV antigen, is unclear. Whether anti-human immunodeficiency virus (HIV)-negative or -positive subjects with an indeterminate RIBA have HCV viremia detectable by polymerase chain reaction was investigated. An indeterminate RIBA was found in 48 (15%) of 318 anti-HIV-negative and 38 (23%) of 167 anti-HIV-positive subjects (P < .05). Clinical stage was IV-C-1 or IV-C-2 in 82% of those anti-HIV-positive. HCV viremia was found more frequently in anti-HIV-positive (89%) than in anti-HIV-negative subjects (50%) with an indeterminate RIBA (P < .05). These results suggest an impaired anti-HCV response associated with HIV infection.

Detection and quantitation of serum HCV-RNA by branched DNA amplification in anti-HCV positive blood donors.

The detection of serum HCV-RNA needs to be standardized. The aim of this study was to assess the effectiveness of the branched DNA amplification method in detecting and quantitating serum HCV-RNA in 54 blood donors, 33 with and 21 without increased serum alanine aminotransferase levels and with detectable serum HCV-RNA by polymerase chain reaction. HCV-RNA was detected by branched DNA signal amplification in 42/54 (77%) of the blood donors. Positivity rates were not different among the 21 blood donors with normal and the 33 blood donors with increased serum alanine aminotransferase levels (86% and 76%, respectively). Median serum HCV-RNA levels were not different among donors with or without increased serum alanine aminotransferase levels (28.6 x 10(5) Eq/ml and 14.7 x 10(5) Eq/ml, respectively). There was no significant correlation between serum alanine aminotransferase levels and serum HCV-RNA levels. These findings show that branched DNA signal amplification identifies most of the donors with true hepatitis C virus viremia and that the level of hepatitis C virus replication is not correlated to serum alanine aminotransferase levels.

Chronic non-B, non-C hepatitis among blood donors assessed with HCV third generation tests and polymerase chain reaction.

Forty five blood donors with increased serum aminotransferases levels had liver histologic assessment and were tested for antibodies to hepatitis C virus (anti-HCV) with second and third generation ELISAs and RIBAs, and for HCV RNA with polymerase chain reaction (PCR) in serum and liver tissue. Twenty-nine of these 45 donors (65%) had steatosis without chronic hepatitis. Sixteen (35%) had chronic hepatitis. Twelve had evidence of HCV infection. Four had no evidence of HCV infection demonstrable by ELISA, RIBA or PCR. These four patients had no known cause of chronic hepatitis and no risk factor for parenterally acquired viral infection was found in them. This observation supports the hypothesis that a non-B, non-C virus might be implicated in chronic hepatitis. However, this hypothesis remains to be demonstrated.

[Collection of anti-HBs hyperimmune plasma: stimulation by Genhevac B in weakly immunized donors]. / Collecte de plasma hyperimmun anti-HBs: stimulation par Genhevac B chez les donneurs faiblement immunisés.

The need for anti HBs globulin is still important in spite of the development of the HBs vaccination. Twenty-two plasma donors, immunized against Hepatitis B virus (HBV) with titers of anti HBs between 100 and 6,000 milli International Units per ml (mUI/ml), received two injections of Genhevac B Pasteur at a one-month interval, and a third injection two months later whenever the answer was still under 6,000 mUI/ml, which is the minimum necessary in order to obtain a specific globulin compatible with the National Standard (100 UI/ml) from plasma fractions. In this programme, no severe adverse reaction was documented, and the mean rate of anti HBs rose from 1,322 to 35,173 mUI/ml, with a mean multiplying factor of 20.2. This result was reached after the first injection in "responders"; the third injection did not increase the titer in "non responders". The titer was still above 6,000 mUI/ml after six months in all the donors with more than 1,500 mUI/ml before vaccination. This limit is suggested to select plasma donors for vaccination, and a booster injection could be proposed every six months.

[Adult celiac disease and type 1 diabetes: a severe and sometimes unknown genetic association]. / Maladie coeliaque de l'adulte et diabète de type 1: une association génétique sévère et parfois méconnue.

In 6 type 1 (insulin-dependent) diabetics, treated with insulin since the age of 2 to 35 years (mean 12), coeliac disease was diagnosed between the 10 th and 73 th years of age (mean 26). Five were of North African origin. Digestive symptoms and severe malnutrition were present in all of them, associated, in the two younger, with a major growth retardation and, in one, multiple pathologic fractures. Biopsy of the small intestine demonstrated, in all, total or subtotal villous atrophy. The metabolic control of diabetes was poor, with frequent hypoglycaemic attacks, induced by minute insulin doses. Severe chronic complications of diabetes were detectable in all of them. Plasma anti-reticulin antibodies were present, at high titer before starting the gluten-free diet, declining slowly after starting this diet, and negative in the patients who followed this diet. Among the genetic markers (which were determined in 4), HLA A1 was present in 4, B8 and DR3 in 3 and DR4 in 3. The DR7 was not detected. The gluten-free diet, memorized by the patients by the use of simple rules, improved the digestive symptoms, and insulin doses could then be increased. The overall prognosis remained poor, due to diabetic complications and sociologic desinsertion. Coeliac disease occurs in 1 to 2% of type 1 diabetics and 4-6% of the coeliac patients are diabetics. Diabetic subjects from North Africa are at high risk of this association. Misdiagnosis of the coeliac disease compromises the metabolic control and nutritional state.(ABSTRACT TRUNCATED AT 250 WORDS)

[Controlled prospective study of clinical and biological thyroid parameters in rheumatoid polyarthritis]. / Etude prospective contrôlée des paramètres thyroïdiens cliniques et biologiques dans la polyarthrite rhumatoïde.

15 patients with rheumatoid arthritis (14 women and 1 man aged between 30 and 75 years) were compared to a control group of 12 women and 1 man (aged between 22 and 77 years) admitted to the rheumatology unit at the same time for benign diseases. Both groups were examined for: the presence of a goitre, family history and/or clinical hormonal dysfunction, the plasma levels of total cholesterol, free thyroxin (FT4), free triiodothyronine (FT3), before and 2 hours after 50 micrograms of thyrotropin IV, thyrostimulin half an hour before and one hour after thyrotropin and the levels of the antimicrosomal anti-thyroid antibodies and the anti-thyroglobulin antibodies. None of the patients with rheumatoid arthritis had any clinical hormonal dysfunction. However, 6 of the 15 patients presented a homogeneous goitre, 5 of these 6 patients had a family history of goitre and 2 had positive antibodies. In comparison with the control group, the 15 cases of rheumatoid arthritis had a significant decrease (m +/- sd) in the FT4 (13.20 +/- 2.50 pmol/l vs 15.60 +/- 2.47; p less than 0.02), FT3 (3.80 +/- 1.12 pmol/l vs 5.50 +/- 0.93; p less than 0.001) and a rise in the T3 with low thyrotropin (5.70 +/- 1.60 vs 8.50 +/- 1.50; p less than 0.001), while the levels of thyrostimulin and the thyrostimulin peak under thyrotropin were not modified.(ABSTRACT TRUNCATED AT 250 WORDS)

[Cost of transfusion in AIDS. Experience at the Claude-Bernard Hospital apropos of 28 cases]. / Coût transfusionnel du SIDA. Expérience de l'hôpital Claude-Bernard à propos de 28 cas.

The study of 28 confirmed cases of AIDS shows that transfused patients use a large amount of hospital's blood products, especially platelets. For these patients, the average cost of transfusion is higher than that, for intensive care unit patient's. The use of irradiated products increases the cost (+ 35%). As there is a shortage of donors, if the present precautions are respected, there is no reason why the hospital should not continue to ask the patient's family and circle of friends, to donate blood.