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Biomedical subjects

F Bailly

Publications and source records attributed to F Bailly.

At least 37 records · Page 2Linked to original sources

A short induction regimen of interferon-alpha is not effective for treatment of relapse in chronic hepatitis C: a randomized trial. For the multicentre GER-CYT-01 group.

The aim of this work was to assess the effect of a high-dose (10 million units, MU) short-duration (14 weeks) interferon-alpha2b (IFN-alpha2b) regimen in relapsers compared with the standard IFN regimen of 3 MU three times weekly (t.i.w.) for 6 months. Fifty-eight non-cirrhotic patients (who had relapsed after previous treatment with IFN) with chronic hepatitis were randomized: 29 to the high-dose, short-duration regimen and 29 to the standard regimen. By the end of IFN therapy, in the high-dose, short-duration group alanine aminotransferase (ALT) normalization was observed in 23 (79%) of 29 patients, and undetectable hepatitis C virus (HCV) RNA in eight (28%) vs 25 (86%) and 11 (38%) of the 29 patients in the standard group, respectively (P = NS). At the end of the 72-week follow-up, in the high-dose, short-duration group a sustained ALT normalization was observed in two (7%) patients, and undetectable HCV RNA in 0 (0%) vs five (17%) and four (14%) patients in the standard group (P = NS). There was less fibrosis improvement in the high-dose, short-duration group (two of 26 patients, 8%) than in the standard group (eight of 25 patients, 32%) (P = 0.04). Tolerance to IFN was good and similar in the two groups. In conclusion, in IFN relapsers, high-dose, short-duration treatment with IFN-alpha has no advantage when compared to a 6-month treatment with 3 MU IFN t.i.w.

Adult↗

Waterborne outbreak of intestinal microsporidiosis in persons with and without human immunodeficiency virus infection.

Among 1454 persons whose stool samples (n=5692) were submitted to a reference laboratory for microsporidia assessment from 1993 to 1996, microsporidia were identified in 338 persons: 261 persons infected with human immunodeficiency virus (HIV), 16 transplant patients, and 61 others. Intestinal microsporidiosis appears to be an endemic disease in HIV-positive persons (prevalence, 0.1%) and a sporadic disease in HIV-negative persons (prevalence, <1/1 million). A waterborne outbreak in 200 persons (attack rate, 1% in HIV-positive patients/month) occurred in the 1995 summer, without evidence of fecal contamination of water. No explanation was found before the outbreak ended, several months before the antiprotease era. Factors associated with microsporidiosis diagnosis were HIV infection, male homosexuality, low CD4 cell counts, and diarrhea. The major factor associated with a diagnosis of microsporidiosis during the outbreak was living in an area corresponding to one of the three water distribution subsystems of the town. Lake contamination was suspected.

Adult↗

[General practice patterns in hepatitis C virus mass screening in the Lyons region].

A study on the screening practices for hepatitis C was carried out among a sample of 786 general practitioners in the Lyon region. The sample comprised three groups: 272 doctors who had participated in a study of this screening, 242 doctors who had not responded to the request for participation, and 272 doctors who had refused to participate. Overall, 88.5% of the doctors surveyed had prescribed at least one HCV serology in the last 12 months, 82% had at least one HCV positive patient and of them, 59.3% had partly or completely screened these patients. The only differences between the three groups are related either to their belonging to an HIV or drug addict care network, or to a particular medical practice (study of allergies, sexology, nutrition, etc.). In fact, the first prescribe more among groups at risk and the second prescribe less and have fewer HCV positive patients.

Factor Analysis, Statistical↗

Tenoxicam, a non-steroid anti-inflammatory drug, is unable to increase the response rate in patients with chronic hepatitis C treated by alpha interferon.

The purpose of this study is to compare a combination of interferon (IFN)-alpha2a (Roferon) + Tenoxicam with IFN-alpha2a alone in the treatment of chronic hepatitis C. This prospective, randomized double-blind study included 149 patients, all of whom were diagnosed with active chronic hepatitis C but non-cirrhotic (ALT > or = 1.5 upper limit of normal, anti-hepatitis C virus (HCV) positive by enzyme-linked immunosorbant assay2 and RIBA3). The patients were randomized in two groups, as follows: G1 (n = 76): IFNalpha2a 3 million units times per week during 6 months + placebo; and G2 (n = 73): IFNalpha2a 3 million units three times per week + Tenoxicam (20 mg/day) during 6 months. Alanine aminotransferase (ALT) and HCV RNA were determined before and at months 6 and 12 of treatment. 2'5' oligoadenylate synthetase activity (2'5' AS) was dosed in mononuclear cells before and at 3-month treatment intervals in 28 patients. Liver biopsy was performed before and 6 months after the end of therapy. Parameters were similar before therapy for both groups. Biochemical and virological responses were similar for both groups at month 6 (49.3% vs. 42.9% and 43.3% vs. 38.3%, respectively) and month 12 (28.3% vs. 23.8% and 17.2% vs. 17.5%, respectively). HCV RNA level significantly decreased in both groups at month 6, with no difference whatever the therapy; however, the HCV RNA level returned to initial values at month 12 and was the only significant prognostic factor of a sustained response. No peak of 2'5' AS activity was observed during treatment in patients with dual therapy. A histological improvement was also noted in both groups without difference, regardless of therapy. The percentage of adverse events was identical for both groups. Paracetamol intake, assessed in 80 patients, was 49.1 g per 6 months in the G1 group and 22.5 g per 6 months in the G2 group (not significant). In conclusion, the non-steroid anti-inflammatory drug, Tenoxicam, does not increase IFNalpha efficacy in the treatment of chronic hepatitis C. This combination is well tolerated and partially lowers Paracetamol intake, but not preexisting alpha-IFN adverse events.

2',5'-Oligoadenylate Synthetase↗

Reinforced regimen of interferon alfa-2a reduces the incidence of cirrhosis in patients with chronic hepatitis C: a multicentre randomised trial. Multicentre GER-CYT-04 Group.

BACKGROUND/AIMS: Our aim was to assess and compare the long-term effect of interferon at standard (6 months) and reinforced dose and duration regimens in chronic hepatitis C. METHODS: A multicentre institutional trial included 244 previously untreated patients with chronic hepatitis C, without cirrhosis, who were randomly allocated to either standard (3 MU thrice a week for 24 weeks; n=120) or reinforced (6 MU daily for 12 days, 6 MU thrice a week for 22 weeks, 3 MU thrice a week for 24 weeks; n=124) regimens. The main endpoint was sustained ALT response at 72 weeks (18 months); secondary end-points were virological (branched DNA and PCR) and histological responses (incidence of cirrhosis) at month 18. RESULTS: Sustained ALT response was observed in five patients (4%, 95% confidence interval 0-8%) in the standard group and in 21 patients (18%, 95% confidence interval 11-25%), from the reinforced group (p=0.002), in agreement with virological response in 21 (81%) patients. Cirrhosis at month 18 was observed in ten (10%) patients in the standard group and one (1%) in the reinforced group (p=0.004). CONCLUSIONS: The standard regimen of interferon, in chronic hepatitis C, confers a minimal sustained response rate at 18 months and may not prevent the occurrence of cirrhosis. Reinforced regimens allow sustained response to be reached in a limited number of patients and reduce the risk of cirrhosis during 18 months of follow-up.

Adult↗

Ribavirin monotherapy in patients with chronic hepatitis C: a retrospective study of 95 patients.

Ribavirin is a purine nucleoside that inhibits the replication of a variety of RNA viruses and was shown to have a transient efficacy in chronic hepatitis C during short-term therapy. We have analysed retrospectively its efficacy in 95 patients with liver biopsy-proven chronic hepatitis C. Patients received oral ribavirin (600-1200 mg daily) for a mean duration of 11 months. Alanine aminotransferase (ALT) levels returned to normal values in 38 patients (40%) and decreased by more than 50% in 20 other patients (21%). HCV RNA clearance from serum was observed in seven patients (8%). The biochemical response rate was higher in patients with chronic hepatitis (54%) than in those with cirrhosis (24%) (P = 0.003). Clearance of HCV RNA was observed in 10% of the patients with chronic hepatitis vs 4% of the patients with cirrhosis. In non-responders to interferon (IFN) therapy, ALT levels returned to normal values in 11 (26%) and HCV RNA became negative in one (2%), as compared to 48% and 3%, respectively, in those contraindicated for IFN. In 17 patients in whom paired liver biopsy specimens were available, the histology activity index (HAI) improved in 12. Therapy was generally well tolerated although 11 patients had to stop therapy because of side-effects, which were more common in cirrhotic patients. In conclusion, our results suggest that long-term administration of ribavirin is well tolerated and may be beneficial in controlling the progression of chronic hepatitis C. This may represent an alternative therapy in patients who have contraindications for interferon therapy or as a palliative approach in non-responders to IFN.

Adult↗

[National study of screening practices for hepatitis C among hemodialysis patients. Hepatitis Group].

French and American consensus conferences on hepatitis C confirmed the burden of that disease, especially in high risk populations. In France, the seroprevalence of HCV is about 20% among haemodialysed patients. This study aimed at describing the French screening practices in haemodialysed patients. In 1995, 1213 self-administered questionnaires were sent to nephrologists working in 715 dialysis units. The response rate was 48% (585/1213) and 485 questionnaires were analysed. In 98% of questionnaires nephrologists answered that they prescribed screening test. Routine screening with alanine amino-transferase (ALT) was reported in 98% of questionnaires, usually once a month (57%) or four times a year (23%). Routine anti-HCV serology was reported by 96%, usually once (28%) or twice (46%) a year. The two main annual strategies combining ALT and anti-HCV serology were 12 ALT and 2 serologies (21%), or 12 ALT and 1 serology (14%) per year. HCV RNA detection was reported mainly in the case of positive anti-HCV serology (70%). The study suggested heterogeneity in screening practices and revealed the need to determine the cost-effectiveness ratios of the various strategies.

Adult↗

Energy metabolism in normal and hypertrophied right ventricle of the ferret heart.

Using an isolated ferret heart preparation (Langendorff perfusion, perfusion pressure 90 mmHg), energy metabolism has been characterized in right and left ventricles from control and hypertrophied hearts. Hypertrophy was induced by pulmonary artery clipping for 30-45 days (right ventricle wall weight/body weight ratio increased by 70%). Myocardial contents of high energy phosphate compounds, glycogen and lactate, and the activities of some enzymes were biochemically measured in perfused hearts and also after ischemic arrest (30 min global ischemia). In hypertrophied right ventricles, PCr (-46%), Cr (-34%) levels, creatine kinase activity (-18%) were significantly decreased compared with control. ATP and Pi levels were not affected by hypertrophy. The adenylate energy charges were similar (0.85-0.86) in both types of heart. The activities of hexokinase (+26%), aldolase (+212%), pyruvate kinase (+14%) and glucose 6-phosphate dehydrogenase (+107%) were increased by hypertrophy. The LDH isozyme pattern was significantly changed such that LDH3 was decreased by 11%, and LDH4 and LDH5 were increased by a factor 1.4 and 2.9 respectively in hypertrophy. After 30 min of global ischemia, PCr level was decreased by 89 and 79% in control and hypertrophied ventricles respectively. ATP level was depressed by 41 in control and only by 21% in hypertrophied muscles. Altogether, the present data suggested that, in the adult ferret heart, the capacity for the ATP synthesis could be maintained during hypertrophy by the enhancement of the glycolytic pathway. The smaller decline of ATP after ischemia in hypertrophied tissue could be explained by a lower consumption of ATP in the hypertrophied compared to the control heart during the earliest period of ischemia.

Adenosine Triphosphate↗

Uncommon side-effects of interferon.

Beside the clinical manifestations usually observed during the treatment of chronic viral hepatitis with interferon, a small number of side-effects, less frequent and sometimes unexpected, have been described. These neurological, pulmonary, metabolic, cardio-vascular or psychiatric manifestations are uncommon but potentially severe. We here describe three cases of stroke that occurred during treatment with interferon in which the role played by the molecule could be questioned.

Adult↗

Comparison of HCV RNA assays for the detection and quantification of hepatitis C virus RNA levels in serum of patients with chronic hepatitis C treated with interferon.

Detection and quantification of hepatitis C virus (HCV) RNA levels by using the standardized qualitative Amplicor HCV and quantitative Amplicor HCV Monitor assays (Roche Molecular Systems) were evaluated in 48 patients with chronic hepatitis C treated with interferon. Results were compared with an in-house reverse transcription and polymerase chain reaction (RT-PCR) assay and the branched DNA (bDNA) assay (Quantiplex, version 1.0, Chiron Diagnostics). Concordance of the qualitative results with the Amplicor HCV and in-house RT-PCR assays occurred in 82% of the samples. All but one of the discrepant specimens were found positive by the Amplicor HCV assay and negative by the in-house RT-PCR. Among the samples with HCV RNA levels measurable with the Amplicor HCV Monitor assay, 22% had HCV RNA titers below the detection limit of the Quantiplex assay. A statistically significant correlation was found between the 2 quantitative assays, although lower titers were obtained with the Amplicor HCV Monitor assay. More important, a good correlation was observed in the evolution of viremia as measured by the 2 assays during interferon therapy. During follow-up of interferon treatments, with the Amplicor HCV Monitor assay, persisting viremia was still detected in 27% of the patients who normalised alanine aminotransferase (ALT), emphasizing the bioclinical relevance of the assay. Pre-treatment serum HCV RNA levels above 10(5) copies/ml were found more frequently in nonresponders than in responders (76% vs. 44%; P < 0.05). Given their great sensitivity and the significant correlations, the Amplicor HCV qualitative and quantitative assays appear useful for the diagnosis and management of hepatitis C infection, and especially for monitoring of therapy.

Adult↗

Predictive value of HIV-1 RNA detection in plasma by branched DNA assay during long-term zidovudine therapy.

The predictive value of human immunodeficiency virus type 1 (HIV-1) RNA detection in plasma using branched DNA assay was studied in a subgroup of 36 asymptomatic HIV-1-infected patients enrolled in a multicenter, double-blind, randomized study. Patients were randomized to receive either zidovudine (AZT) 1 g/day or placebo and were monitored for a mean time of 61 months. HIV-1 RNA was detected in plasma using branched DNA assay at months 0, 6, 12, 24, and 36. HIV-1 RNA was detected at levels of > or = 10(4) RNA eq/ml (eq/ml) in 8.3% of the patients at baseline, and this percentage increased during the first two years in the placebo group only. The detection rate of HIV-1 RNA at three years was 50% in both the AZT and the placebo groups. HIV-1 RNA levels ranged from 10(4) to 478 x 10(3) RNA eq/ml. HIV-1 RNA was detected at levels of > or = 10(4) eq/ml a mean time of 19 +/- 13 months before progression to AIDS in 76.5% of progressing patients. In a multivariate analysis including baseline CD4+ count, the initial randomization group, HIV-1 RNA detection in plasma, and detection of p24 antigenemia during the first three years of follow-up, the best independent predictors of progression to AIDS at five years and the best independent predictors of death at five years were HIV-1 RNA detection in plasma and p24 antigenemia.

Acquired Immunodeficiency Syndrome↗

Magnitude and management of HCV infection in France.

The prevalence of hepatitis C virus infection in the general population in France averages 1%. The majority of these patients are viremic with detectable HCV-RNA. Further, 75% of these individuals did not suspect they were at risk for being HCV carriers. Less than 10% of HCV carriers in France have been identified and even fewer have been treated with interferon. In addition to infection following intravenous drug use, preliminary studies suggest that most newly infected patients have become infected following surgery or endoscopy without transfusion. A large serological study of patients scheduled for surgery identified 4% HCV carriers. Other studies have determined that more than 8% of patients who received prior transfusions are now anti-HCV positive. These findings prompted the French government to initiate a screening program in France to identify patients at risk for HCV infection. This national program also involves the establishment of regional HCV reference centers to coordinate efforts among hospitals, gastroenterology/hepatology specialists, and general practitioners. The mission of the program is to promote screening and disseminate appropriate clinical practice guidelines for the management of HCV infection. The goal is to identify infected patients and initiate optimal interferon therapy as early as possible in the course of HCV infection to prevent the long-term complications secondary to infection.

Carrier State↗

Cytomegalovirus DNA level on biopsy specimens during treatment of cytomegalovirus gastrointestinal disease.

BACKGROUND & AIMS: There is no clear and point for the response to treatment of gastrointestinal human cytomegalovirus (HCMV) disease. HCMV-DNA quantitation on gastrointestinal biopsy specimens has proven its value for the diagnosis of gastrointestinal HCMV disease in patients with acquired immunodeficiency syndrome (AIDS). The aim was to study HCMV-DNA levels on gastrointestinal biopsy specimens during the treatment of gastrointestinal HCMV disease. METHODS: HCMV-DATA quantitation was performed using two different polymerase chain reaction assays on 90 biopsy specimens obtained before anti-HCMV therapy, during the induction phase, or during maintenance therapy for gastrointestinal HCMV disease in 21 patients with AIDS. RESULTS: HCMV-DNA was detected on all the biopsy specimens ranging from 9 to > or = 80,000 Eq/0.1 microgram DNA. Pretherapeutic mean level was 69,000 +/- 27,000 Eq/0.1 microgram DNA. Induction therapy was followed by a mean decrease of 1.7 +/- 1.3 log10 Eq/0.1 microgram DNA. HCMV-DNA levels decreased during induction therapy to < 1000 Eq/0.1 microgram DNA in 60% of patients but remained > 80,000 Eq/0.1 microgram DNA in 20% of patients. Relapse occurred in all the patients in a mean time of 100 days. HCMV-DNA level at the end of the induction phase seems to influence the time to relapse. CONCLUSIONS: Quantitation of HCMV-DNA on gastrointestinal biopsy specimens seems to be useful for monitoring gastrointestinal HCMV disease in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

Treatment of HCV liver disease by recombinant interferon alpha.

Interferon alpha has confirmed its efficacy for the therapy of chronic hepatitis C. Half of the patients treated will normalize their plasma ALT at the end of a 6-month course of 3 MU thrice a week. This biochemical response is associated with a reduction of HCV RNA (viraemia) from serum and with significant improvement of liver histology. Despite those beneficial effects, 50% of treatment responders generally relapse after treatment arrest. Increasing doses to 6 MU and/or the duration of interferon therapy increases the proportion of long-term sustained responders. Combining therapy with ribavirin, a nucleoside analogue, also appears to have a similar effect.

Alanine Transaminase↗

Treatment of chronic hepatitis C: another therapeutic option.

Ribavirin is a nucleoside analogue with anti-viral activity against a number of DNA and RNA viruses. That molecule is administered per os and its most frequent adverse effect is haemolysis, moderate in most cases. Used alone, ribavirin normalized liver enzyme concentrations in 45% of patients while viraemia is not significantly modified. Histological improvement is observed in responder patients. The most interesting results have been obtained by associating ribavirin with interferon. In patients who have never been treated, a six-month course of ribavirin-interferon association produced a lasting and total response in 47% of patients versus 25% in patients treated with interferon alone. In relapsers, this bi-therapy produced total and prolonged response in more than 40% of cases and in 20% of non-responder patients. Lastly, that association appears promising in treating hepatitis C reinfection after liver transplantation.

Antiviral Agents↗

Stability of hepatitis C virus RNA in serum from samples collected in a closed-tube system for serum separation and transport, as measured by a quantitative competitive PCR assay.

Recovery of hepatitis C virus (HCV) RNA, after variable time intervals from collection, was assessed using a closed-tube system for collection, separation and transport (SST tubes). Blood from four hepatitis C-infected patients was collected in 12 SST tubes and centrifuged within 1 to 3 h of collection. Tubes were then left 0, 8, 12, 24, 48 and 72 h at room temperature and at 4 degrees C before removing serum. Hepatitis C virus RNA levels were measured by quantitative polymerase chain reaction (PCR) using the AMPLICOR HVC MONITOR assay. Hepatitis C virus RNA levels in these samples were stable for at least three days at both temperatures. Polymerase chain reaction signals never decreased by more than 0.5 log. The reproducibility of the assays showed that the quantitative PCR method can be used with the storage conditions tested here. Our data suggests that processing blood in SST tubes may be very useful in following hepatitis C virus RNA titres in infected patients, especially those receiving treatment.

Hepacivirus↗