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Jean-Pierre Vinel

Publications and source records attributed to Jean-Pierre Vinel.

At least 19 recordsLinked to original sources

Amanita phalloides poisoning: reassessment of prognostic factors and indications for emergency liver transplantation.

BACKGROUND/AIMS: Amanita phalloides poisoning is an uncommon cause of acute liver failure with an especially rapid course. The aim of this study was to re-assess transplantation criteria in patients with mushroom poisoning. METHODS: Twenty-seven patients admitted for Amanita phalloides poisoning were studied. Previously reported transplantation criteria, including the recent Ganzert's criteria, were tested retrospectively. RESULTS: The rate of fatal intoxication (death and/or transplantation) was 8/27 (30%). An interval between ingestion and diarrhea <8h was a very early predictor of a fatal outcome (accuracy of 78%). Later on, non-paracetamol and paracetamol King's College criteria were superior to Clichy's and Ganzert's criteria (accuracy of 100% compared to 85% and 85%, respectively). Encephalopathy and renal insufficiency were not constant in the fatal intoxication group. Prothrombin index below 10% 4 days or more after ingestion had a 100% accuracy for predicting a fatal outcome. CONCLUSIONS: Liver transplantation should be strongly considered in patients with an interval between ingestion and diarrhea <8h. Encephalopathy should not be an absolute prerequisite for deciding transplantation. From day 4 after ingestion, prothrombin index lower than 10% ( approximately INR of 6) alone is a reliable tool for deciding emergency transplantation.

Adult↗

Twenty-four hour kinetics of hepatitis C virus and antiviral effect of alpha-interferon.

Numerous studies reported that patients infected by the genotype 1 of hepatitis C virus (HCV) and/or with a high baseline viral load responded poorly to antiviral therapy. Study of viral kinetics has provided clues to the understanding of non-response to alpha-interferon (IFN-alpha)-based therapy. The objective of this study was to clarify the influence of viral factors such as the genotype and baseline viral load on HCV resistance to treatment through the study of their impact on the first phase of viral decline. HCV RNA levels were determined frequently following the administration of 3 million units of IFN-alpha in 22 chronic HCV carriers. The evolution of HCV RNA level over 24 hr was different in genotype 1-infected patients, compared to that in patients infected by other genotypes. The viral load decline at 24 hr was lower in patients with genotype 1. Patients with a high baseline viral load exhibited a viral dynamics different from patients with a lower level of viremia; the extent of the first phase was also lower in these patients. Non-responder patients had a slower viral decay on day 1 of therapy than patients who cleared the virus under treatment. In conclusion, 24 hr HCV dynamics is regulated by genotype and baseline viral load. Genotype 1 strains and those that produce high viral loads are the most resistant to the antiviral action of IFN-alpha. Resistant HCV strains could be distinguished from sensitive viruses as early as a few hours after the beginning of the treatment.

Adult↗

Hepatitis E is an autochthonous disease in industrialized countries. Analysis of 23 patients in South-West France over a 13-month period and comparison with hepatitis A.

OBJECTIVES: Hepatitis E virus (HEV) is responsible for acute hepatitis predominantly in developing countries. In Western Europe and in the US, cases of acute HEV infection are uncommon and occur primarily in travelers returning from endemic countries. The aim of this study was to describe patients with acute hepatitis E in South West France and compare them with patients with acute hepatitis A. METHODS: 23 consecutive patients over 13 months were analysed. Acute hepatitis E was diagnosed on the presence of specific serum antibodies or viral RNA detection in serum or stools. Real time PCR products from viraemic patients were sequenced. RESULTS: All the HEV sequences belonged to genotype 3. Two patients (8%) died during their hospital stay, both suffered from severe underlying disease. Only 3 patients (13%) had travelled outside of Europe, within 3 months of the onset of disease. When compared to 23 patients with acute hepatitis A at the same hospital and during the same time frame, HEV-infected patients were older (54.4 +/- 16.6 vs 24.5 +/- 16.6, P<0.05), had lower ALT levels (55.4 X upper normal limit +/- 48.6 vs 107.8 X upper normal limit +/- 82.8, P<0.05) and had lower incidence of recent travel outside of Europe (13% in the hepatitis E group vs 60% in the hepatitis A group, P<0.05). CONCLUSIONS: Hepatitis E can be considered an autochthonous infection in South West France. All strains sequenced were related to genotype III. When compared to hepatitis A, HEV-infected patients were older, had lower ALT levels and had a lower incidence of travel outside of Europe.

Adult↗

Changes in French people's misconceptions about hepatitis C, 1997-2003.

OBJECTIVE: The French health authorities instituted in 1999 a campaign to educate physicians, high-risk populations, and the public about hepatitis C (HC). To what extent has knowledge about HC increased among members of the French public? METHOD: A convenience sample of 706 French adults, aged 18 to 87, completed in 2003 a questionnaire designed to assess their knowledge of HC. Their responses were compared to those in 1997 of a different group of French adults on an identical questionnaire. RESULTS: Between 1997 and 2003, knowledge significantly improved on 13 of the 26 items for which strong expert-public differences were found in 1997 and significantly worsened on 3 items. CONCLUSIONS: France's public education campaign led to only a limited increase in knowledge about HC. Further public education is needed.

Adolescent↗

Complications of portal hypertension in adults: a French consensus.

Portal hypertension is responsible for different severe complications such as variceal bleeding, ascites and pulmonary disorders. Different pharmacological and endoscopic treatments have been proposed but some recommendations may differ. The conclusions of a French consensus conference on the prevention and treatments of the main complications of portal hypertension in adults are reported.

Adrenergic beta-Antagonists↗

Heterogeneity of hepatitis C virus genotype 4 strains circulating in south-western France.

Hepatitis C virus (HCV) is a major cause of liver disease. Knowledge of HCV variability is crucial for clinical and epidemiological analysis. HCV genotype 4 (HCV-4) has become increasingly prevalent in European countries, including France, in recent years. The present study investigates the heterogeneity of HCV-4 in south-western France by phylogenetic analysis of NS5B sequences from 166 patients. The E2 region of 90 strains was also analysed. Genotype 4 accounts for 7.4 % of HCV infections in this area. Analysis of the NS5B region revealed 12 subtypes and the NS5B and E2 phylogeny data were congruent, except for one strain. The epidemiological data indicated two main groups of patients. One included intravenous drug users (IVDUs) of French origin, who were infected by homogeneous strains of subtypes 4a or 4d. The second group comprised non-IVDU patients who were infected with heterogeneous strains. This group was subdivided into patients of French origin, who were infected with eight subtypes, and patients from non-European countries (Central Africa or the Middle East), who were mainly infected with 4f, 4k, 4r and other subtypes; they showed the greatest genetic heterogeneity. This study of a large cohort of patients shows the great diversity of HCV-4 strains, and that these subtypes have spread differently.

Adult↗

Treatment of hepatorenal syndrome as defined by the international ascites club by albumin and furosemide infusion according to the central venous pressure: a prospective pilot study.

OBJECTIVE: Hepatorenal syndrome (HRS) is a functional renal failure that occurs late during cirrhosis. The prognosis is extremely poor with a mean survival of 1.7 wks from the time of diagnosis. The aim of the present study was to examine the effects of albumin and furosemide administration tailored to central venous pressure (CVP) on renal function and clinical outcome. METHODS: We treated 20 consecutive patients with HRS. Albumin was given to increase and/or maintain CVP above 3 cm H(2)O. If diuresis remained below 50 mL/h despite effective volume expansion, furosemide was administrated. Patients were considered responders and treatment was discontinued when creatinine clearance rose above 40 mL/min or serum creatinine fell under 132 mumol/L. RESULTS: The need for albumin varied from patient to patient (extremes 40-600 g) and in the same patient from day to day. All but one needed furosemide. Eleven patients (55%) responded to treatment. In this population, diuresis, serum creatinine, and creatinine clearance were all significantly improved. Creatinine clearance at baseline was predictive of treatment efficacy. Survival increased in these patients compared to nonresponders defined as patients with no improvement in renal function (259 days +/- 113 compared to 14 days +/- 3, p < 0.0005). Response to treatment and the type of HRS were the only variables with an independent prognostic value. CONCLUSION: This study shows that HRS as defined by the International Ascites Club can be treated by albumin administration alone or with furosemide given according to the patient's specific need using CVP.

Adult↗

Evolution of hepatitis C virus quasispecies during therapy with IL2 combinated to alpha interferon and ribavirin.

This study analyses the impact of interleukin 2 (IL2) combined with alpha interferon (IFN-alpha) and ribavirin on the heterogeneity of hepatitis C virus (HCV). We studied 10 patients who took part in a clinical trial that assessed the effects of retreatment with IL2, IFN-alpha and ribavirin in patients who failed to clear the virus after a previous bitherapy. The heterogeneity of HCV quasispecies was assessed by cloning and sequencing the hypervariable region 1 (HVR1) in samples obtained at baseline (W0), after 12 weeks of treatment with IFN-alpha and ribavirin (W12), after a cycle of administration of IL2 in combination with the classical bitherapy (W21 and W24) in the eight patients who failed to clear the virus under treatment. The mean viral load at W21 and at W24 was not different from that at W12. The heterogeneity of HVR1 quasispecies after the administration of IL2 was not different from that at baseline or after 12 weeks of bitherapy. Furthermore, the proportion of nonsynonymous substitutions was unchanged after the IL2 cycles. Thus, the efficacy of the tritherapy with IL2, IFN-alpha and ribavirin is similar to that of the classical bitherapy. Treatment with IL2 in combination with IFN-alpha and ribavirin had no effect on the selective pressure on HCV quasispecies. IL2 is not the best option to treat hepatitis C.

Adult↗

Treatment of murine hepatocellular carcinoma using genetically modified cells to express interleukin-12.

BACKGROUND AND AIM: The majority of patients cannot benefit from the conventional curative treatments that are currently used for hepatocellular carcinoma (HCC), which remains a world health problem. Interleukin (IL)-12 is one of the most potent anti-tumor cytokines. The aim of the present study was to examine the anti-tumor effect and toxicity of intrahepatic delivery of IL-12 using an ex vivo gene therapy approach in a murine model of HCC. METHODS: Syngenic fibroblasts or MM45T-Li HCC tumor cells were genetically modified in vitro to express IL-12 using a polycistronic TFG murine IL-12 retroviral vector (TFGmIL-12) coding for both p35 and p40 murine IL-12 subunits. Hepatocellular carcinoma was generated using direct intrahepatic inoculation of the tumor cell line into the left liver lobe of BALB/c mice. RESULTS: Direct liver expression of IL-12 by the injected genetically modified tumor cells induced a marked inhibition of tumor growth. This effect was associated with an early infiltration of macrophages, and lymphocytes forming numerous intralobular foci. There was no significant liver toxicity, as shown by normal biochemical liver tests. At a later time, the intralobular foci were rare and consisted mainly of CD4+ T cells, while CD8+ T cells were present in the lobule. Intrahepatic expression of IL-12 did not modify circulating or splenic B lymphocytes or natural killer (NK) cells. The inhibition of tumor growth was maintained in nude mice even when depleted in NK cells. Importantly, in a second model, treatment of established day 7 liver tumors in BALB/c mice using direct intra-tumor injection of syngenic fibroblasts that were genetically modified to express IL-12 significantly reduced tumor size. CONCLUSION: In conclusion, these data provide evidence that experimental HCC can be efficiently and safely treated using ex vivo IL-12 gene therapy, which seems promising for future clinical studies.

Animals↗

Convenient biological assay for polyethylene glycol-interferons in patients with hepatitis C.

The vesicular stomatitis virus cytopathic effect reduction assay is suitable to quantify polyethylene glycol-alpha interferon 2a (PEG-IFN-alpha 2a) and PEG-IFN-alpha 2b. Human serum and ribavirin did not interfere with the assay. This bioassay was successfully used for assaying PEG-IFN-alpha 2a and PEG-IFN-alpha 2b in serum samples from patients undergoing combination therapy.

Animals↗

Follow-up of adverse drug reactions from peginterferon alfa-2b-ribavirin therapy.

STUDY OBJECTIVE: To investigate the adverse drug reactions (ADRs) from peginterferon alfa-2b plus ribavirin in patients infected with the hepatitis C virus (HCV). DESIGN: Prospective, observational, pharmacovigilance study. SETTING: Gastroenterology department of a French university hospital. PATIENTS: A cohort of consecutive outpatients who were treated with peginterferon alfa-2b plus ribavirin for viral hepatitis. INTERVENTION: During the 1-year period of HCV therapy visits, a medical staff member trained in pharmacovigilance interviewed the patients about all ADRs and their use of other drugs. The ADRs assessed as serious were confirmed from regular review of the medical records. MEASUREMENTS AND MAIN RESULTS: A total of 87 patients were treated for HCV. Among these, peginterferon alfa-2b plus ribavirin therapy was started in 51 patients; one patient was lost to follow-up after 1 month. The ADRs were assessed as serious in 10 patients (20%): suicide (one patient), hospitalization (three patients), and definitive discontinuation of peginterferon alfa-2b plus ribavirin (six patients). The ADRs contributed to or were the main reason for withdrawing HCV drugs in 8 patients (16%). Dosage reductions of ribavirin and/or peginterferon alfa-2b were required in 10 patients (20%) and seemed less frequent than that needed in clinical trials. Compared with results of clinical trials, a similar frequency of hair loss, higher frequency of injection-site reactions, lower frequency of depression or insomnia, and higher frequency of endocrine ADRs or blurred vision were detected. CONCLUSION: Results suggest some differences in the frequencies of ADRs compared with data from clinical trials. A longer period of monitoring is warranted to improve knowledge about ADRs of pegylated interferon. A medical staff member trained in pharmacovigilance is useful to collect quantitative and qualitative data about ADRs.

Adult↗

Clinicopathological forms and prognostic index in Budd-Chiari syndrome.

BACKGROUND: A recent study in patients with Budd-Chiari syndrome showed the value of a prognostic index including age, Pugh score, ascites and serum creatinine. Surgical portosystemic shunt did not appear to improve survival. AIMS: To validate these findings in an independent sample; to evaluate a classification into three forms according to the presence of features of acute injury, chronic lesions, or both of them (types I, II or III, respectively); and to assess whether taking into account this classification would alter our previous conclusions. METHODS: Multivariate Cox model survival analysis, first on 69 new patients; second, on these 69 and 54 previous patients, all diagnosed since 1985. RESULTS: Previous prognostic index had a significant prognostic value (P<0.0001) which was further improved by taking into account type III form (P<0.001). Type III form was associated with the poorest outcome. No significant impact of surgical shunting on survival was disclosed. CONCLUSIONS: The prognosis of Budd-Chiari syndrome can be based on age, Pugh score, ascites, serum creatinine and the presence of features indicating acute injury superimposed on chronic lesions (type III form). The idea that surgical shunting has no significant impact on survival is reinforced by these findings.

Adolescent↗