Jean-Pierre Vinel

Centre Hospitalier Universitaire de Toulouse, Tolosa de Llenguadoc, Midi-Pyrénées, France

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Publications (58)407.04 Total impact

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    ABSTRACT: Hepatitis E virus (HEV) genotypes 3 and 4 cause sporadic cases of infection in developed countries. Being elderly and having an underlying liver disease are the main risk factors for death in this population. Chronic infection has been described in immunocompromised patients. Ribavirin is now the anti-viral treatment of choice in solid-organ-transplant recipients with chronic HEV infection. We hypothesized that early short-term treatment of acute HEV infection may be useful for patients with risk factors or undergoing chemotherapy. Between July 2010 and January 2014, 21 patients diagnosed with acute HEV infection were treated with ribavirin, at 600-800 mg/day for up to 3 months. All serum samples were positive for HEV RNA. Nine patients were treated for severe hepatitis. Six patients were aged >70 years. Four patients were receiving an immunosuppressive therapy for an autoimmune disease and two patients were undergoing chemotherapy for a malignancy. Two patients received a fixed-dose regimen. For all other patients, ribavirin was stopped when HEV became undetectable in the serum. The median duration of ribavirin treatment was 26 days. Two patients developed severe anemia. Two patients with encephalopathy died. One patient relapsed transiently. All patients were cleared of HEV and regained normalized liver-enzyme levels. Immunosuppressive treatment and chemotherapy could be resumed. Treatment of acute HEV infection using ribavirin seems safe and effective. Short-term treatment tailored to viremia may be the best regimen for this indication. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · Jul 2015 · Liver international: official journal of the International Association for the Study of the Liver
  • Christophe Bureau · Jean-Pierre Vinel

    No preview · Article · Jul 2014 · Hepatology
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    ABSTRACT: Elafin, a natural protease inhibitor expressed in healthy intestinal mucosa, has pleiotropic anti-inflammatory properties in vitro and in animal models. We found that mucosal expression of Elafin is diminished in patients with inflammatory bowel disease (IBD). This defect is associated with increased elastolytic activity (elastase-like proteolysis) in colon tissue. We engineered two food-grade strains of lactic acid bacteria (LAB) to express and deliver Elafin to the site of inflammation in the colon to assess the potential therapeutic benefits of the Elafin-expressing LAB. In mouse models of acute and chronic colitis, oral administration of Elafin-expressing LAB decreased elastolytic activity and inflammation and restored intestinal homeostasis. Furthermore, when cultures of human intestinal epithelial cells were treated with LAB secreting Elafin, the inflamed epithelium was protected from increased intestinal permeability and from the release of cytokines and chemokines, both of which are characteristic of intestinal dysfunction associated with IBD. Together, these results suggest that oral delivery of LAB secreting Elafin may be useful for treating IBD in humans.
    Full-text · Article · Oct 2012 · Science translational medicine
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    ABSTRACT: Transjugular liver biopsy (TJLB) is usually performed when a percutaneous liver biopsy (PLB) is contraindicated. TJLB is an invasive procedure and the patient's tolerance may be variable. To compare patient tolerance and quality of the biopsy sample between PLB and TJLB. A total of 143 patients underwent a liver biopsy; of these, 75 underwent TJLB and 68 underwent PLB. To evaluate patient tolerance, we used a visual analog scale that scored the intensity of the symptoms. The length of the biopsy sample and the total number of portal tracts per biopsy were also determined for assessment of biopsy quality. The biopsy sample length was similar in both groups (18.88±8.83 mm on PLB vs. 18.26±10.30 mm on TJLB). No differences were found in the number of portal tracts between the two groups (10.43±8.25 on TJLB vs. 12±10.09 on PLB). Fewer complications were observed in the TJLB group compared with the PLB group (P=0.002).Further, higher degree of pain was reported by patients who underwent PLB compared with patients who underwent TJLB (3.18±3.17 vs. 1.19±2.07); as such, there was a greater need for analgesics on PLB. TJLB and PLB techniques provide similar quality of tissue samples; however, TJLB is less painful and therefore better tolerated by patients.
    Full-text · Article · Jun 2012 · European journal of gastroenterology & hepatology

  • No preview · Article · May 2012 · Gastroenterology
  • Christophe Bureau · Philippe Otal · Jean-Pierre Vinel
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    ABSTRACT: Within the last 20 years, the transjugular intrahepatic portal stent (TIPS) has gained its place in the therapeutic armamentarium for the complications of portal hypertension. Randomized controlled trials have shown that TIPS is more effective than other available treatments to reduce recurrence of refractory ascites, to control acute variceal hemorrhage, and to prevent variceal rebleeding. However, in all these clinical settings, TIPS increases the risk of hepatic encephalopathy and does not improve survival. Initially, the main drawback of the technique was shunt dysfunction, which was observed in up to 80% of patients within 2 years. This rate was tremendously reduced when PTFE-covered stents were used instead of bare ones. Most published trials were performed using the latter devices, so their results should be reassessed using covered stents. Thanks to the experience accumulated over the last two decades, better patient selection could also improve the results of TIPS.
    No preview · Chapter · Apr 2012
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    ABSTRACT: Depletion of CD4+ T cells from the gut occurs rapidly during acute HIV-1 infection. This has been linked to systemic inflammation and disease progression as a result of translocation of microbial products from the gut lumen into the bloodstream. Combined antiretroviral therapy (cART) substantially restores CD4+ T cell numbers in peripheral blood, but the gut compartment remains largely depleted of such cells for poorly understood reasons. Here, we show that a lack of recruitment of CD4+ T cells to the gut could be involved in the incomplete mucosal immune reconstitution of cART-treated HIV-infected individuals. We investigated the trafficking of CD4+ T cells expressing the gut-homing receptors CCR9 and integrin α4β7 and found that many of these T cells remained in the circulation rather than repopulating the mucosa of the small intestine. This is likely because expression of the CCR9 ligand CCL25 was lower in the small intestine of HIV-infected individuals. The defective gut homing of CCR9+β7+ CD4+ T cells - a population that we found included most gut-homing Th17 cells, which have a critical role in mucosal immune defense - correlated with high plasma concentrations of markers of mucosal damage, microbial translocation, and systemic T cell activation. Our results thus describe alterations in CD4+ T cell homing to the gut that could prevent efficient mucosal immune reconstitution in HIV-infected individuals despite effective cART.
    Preview · Article · Dec 2011 · The Journal of clinical investigation
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    ABSTRACT: Detection of small hepatocellular carcinoma (HCC) eligible for curative treatment is increased by surveillance, but its optimal periodicity is still debated. Thus, this randomized trial compared two ultrasonographic (US) periodicities: 3 months versus 6 months. A multicenter randomized trial was conducted in France and Belgium (43 sites). Patients with histologically proven compensated cirrhosis were randomized into two groups: US every 6 months (Gr6M) or 3 months (Gr3M). For each focal lesion detected, diagnostic procedures were performed according to European Association for the Study of the Liver guidelines. Cumulative incidence of events was estimated, then compared using Gray's test. The prevalence of HCC ≤30 mm in diameter was the main endpoint. A sample size of 1,200 patients was required. A total of 1,278 patients were randomized (Gr3M, n = 640; Gr6M, n = 638; alcohol 39.2%, hepatitis C virus 44.1%, hepatitis B virus 12.5%). At least one focal lesion was detected in 358 patients (28%) but HCC was confirmed in only 123 (9.6%) (uninodular 58.5%, ≤30 mm in diameter 74%). Focal-lesion incidence was not different between Gr3M and Gr6M groups (2-year estimates, 20.4% versus 13.2%, P = 0.067) but incidence of lesions ≤10 mm was increased (41% in Gr3M versus 28% in Gr6M, P = 0.002). No difference in either HCC incidence (P = 0.13) or in prevalence of tumors ≤30 mm in diameter (79% versus 70%, P = 0.30) was observed between the randomized groups. Conclusion: US surveillance, performed every 3 months, detects more small focal lesions than US every 6 months, but does not improve detection of small HCC, probably because of limitations in recall procedures.
    Full-text · Article · Dec 2011 · Hepatology
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    ABSTRACT: Colonic tissues of patients with inflammatory bowel disease have been reported to have increased proteolytic activity, but no studies have clearly addressed the role of the balance between proteases and antiproteases in the pathogenesis of colitis. We investigated the role of Elafin, a serine protease inhibitor expressed by skin and mucosal surfaces in human inflammatory conditions, and the proteases neutrophil elastase (NE) and proteinase-3 (PR-3) in mice with colitis. We studied mice with heterozygous disruptions in NE and PR-3, mice that express human elafin (an inhibitor of NE and PR-3), and naïve mice that received intracolonic adenoviral vectors that express elafin. Trinitrobenzene sulfonic acid (TNBS) or dextran sodium sulphate (DSS) was used to induce colitis. Protease, cytokine levels, and NF-κB activity were measured in colons of mice. Caco-2 and HT29 cells were studied in assays for cytokine expression, permeability, and NF-κB activity. Elafin expression or delivery re-equilibrated the proteolytic balance in inflamed colons of mice. In mice given TNBS or DSS, transgenic expression of elafin or disruption of NE and PR-3 protected against the development of colitis. Similarly, adenoviral delivery of Elafin significantly inhibited inflammatory parameters. Elafin modulated a variety of inflammatory mediators in vitro and in vivo and strengthened intestinal epithelial barrier functions. The protease inhibitor Elafin prevents intestinal inflammation in mouse models of colitis and might be developed as a therapeutic agent for inflammatory bowel disease.
    No preview · Article · Apr 2011 · Gastroenterology
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    ABSTRACT: BACKGROUND & AIMS:: Colon tissues of patients with inflammatory bowel disease (IBD) have been reported to have increased proteolytic activity, but no studies have clearly addressed the protease to anti-protease balance in the pathogenesis of colitis. We investigated the role of Elafin, a serine protease inhibitor expressed by skin and mucosal surfaces in human inflammatory conditions, and the proteases neutrophil elastase (NE) and proteinase-3 (PR-3), in mice with colitis. METHODS:: We studied mice with heterozygous disruptions in NE and PR-3and 2 strains of mice that express transgenic human elafin (an inhibitor of NE and PR-3). Trinitrobenzene sulfonic acid (TNBS) or dextran sodium sulphate (DSS) was used to induce colitis. Protease and cytokine levels were measured in colonic tissues collected from the mice. CaCO(2) and HT29 cells were studied in assays for cytokine expression and permeability. RESULTS:: Mice that expressed transgenic elafin developed less colitis and had reduced levels of proteases than wild-type mice following administration of TNBS or DSS. Expression of elafin did not modify activities of elastase or PR-3, but inhibited their increase upon the induction of colitis. Mice that expressed reduced levels of NE and PR-3 were protected against DSS-induced colitis. Elafin expression altered the patterns of inflammatory mediators and strengthened intestinal epithelial barrier functions in cells and colonic tissues from mice. CONCLUSIONS:: The protease inhibitor Elafin prevents intestinal inflammation in a mouse model of colitis and might be developed as a therapeutic agent for IBD.
    Full-text · Article · Apr 2011 · Gastroenterology

  • No preview · Article · Jan 2011 · Gastroenterology
  • Christophe Bureau · Philippe Otal · Jean-Pierre Vinel
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    ABSTRACT: Interventional radiology techniques, namely embolization and shunting, were developed mainly to deal with the failures of drug and/or endoscopic treatments. Among those techniques, the transjugular intrahepatic portosystemic shunt (TIPS) is the only that aims to normalize portal pressure and is therefore able to treat both refractory bleeding and intractable ascites. Embolization of esophago-gastric or ectopic varices, balloon occluded retrograde transvenous obliteration of varices, or partial splenic embolization have been poorly evaluated. Severe complications may be observed and since portal hypertension is maintained or even increased, these procedures have only a transient effect with a high rebleeding rate. Their role should be explored in patients with uncontrolled variceal hemorrhage who have a contraindication for TIPS, such as pulmonary arterial hypertension, congestive heart failure, liver failure, or severe or recurrent encephalopathy. Nowadays, TIPS should be performed using PTFE-covered prostheses, which were shown to decrease the rate of shunt dysfunction and improve clinical outcomes. TIPS has been found more effective than drug and/or endoscopic treatments in controlling active variceal bleeding as well as in preventing rebleeding, though survival was not improved and encephalopathy was more frequent. It can also be used for gastric or ectopic varices. In refractory ascites, TIPS was shown to be more effective than large ­volume paracenteses. It has also been successfully used in hydrothorax. KeywordsInterventional radiology-Embolization-TIPS-Variceal bleeding-Refractory ascites-Cirrhosis-Portal-hypertension
    No preview · Chapter · Dec 2010
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    Preview · Article · Dec 2010
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    ABSTRACT: KLF6 protein is a transcription factor that plays important functions in hepatocellular carcinoma (HCC), which is one of the leading causes of death by cancer worldwide. Previous studies showed the existence of three splice variants of KLF6, termed SV1, SV2, and SV3. An increased SV1/KLF6 mRNA ratio in HCC was already described. In this study, we aimed to investigate the expression of the SV2 variant in HCC samples and its role in hepatic cells. We measured the expression of the SV2 variant in HCC and adjacent tissue samples by q-RT-PCR. We established IHH and HepG2 stable cell lines over-expressing the SV2 variant and measured cell growth and apoptotic rate. We observed a reduced expression of the SV2 variant in HCC samples versus surrounding tissues and normal liver. Interestingly, our findings demonstrate that the over-expression of the SV2 variant in IHH and HepG2 cells leads to a significant reduction of proliferation associated with cell death by apoptosis. We further demonstrate that the SV2 expression leads to an induction of the cell-cycle-controlling p21(CIP/WAF1) and the pro-apoptotic Bax genes, mediated by the p53 protein. We show further that the SV2 expression in IHH and HepG2 cells induces their sensitivity to the anti-cancer drug, gemcitabine. We reveal a reduced expression of the SV2 variant of KLF6 in HCC samples and describe anti-proliferative and pro-apoptotic functions for this variant in hepatic cells.
    Full-text · Article · Nov 2010 · Journal of Hepatology
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    ABSTRACT: Hepatitis E virus (HEV) is transmitted via the fecal-oral route and locally acquired sporadic hepatitis E can occur in Western countries. Chronic hepatitis E virus infections have been recently described in solid organ transplant recipients. There is little data on the evolution of hepatitis E in patients immunocompromised for other reasons. The aim of this study was to evaluate the clinical course of hepatitis E in patients immunocompromised because of hematological malignancies. Starting on November 2003, all patients in the Toulouse University Hospital Hematology Department with unexplained elevated transaminases were tested for hepatitis E using viral RNA detection in serum or stools and serology. Acute hepatitis E was diagnosed in six middle-aged hematology patients. All cases were autochthonous. HEV strains were genotype 3. All patients had a significant increase of transaminases (6-95 upper limit normal) and only two had HEV IgG. Five patients were asymptomatic and one had jaundice. Transmission of HEV occurred between two patients who had overlapping stays in the hematology ward. All five evaluable patients ultimately cleared their HEV but viremia was prolonged over 6 months in three patients and specific treatment had to be postponed in two patients. Screening for HEV should be carried out routinely in hematology patients with elevated transaminases, and patient-to-patient transmission is a concern. Further studies are required to determine whether management of malignancy, particularly stem-cell transplantation should be adapted to HEV status.
    No preview · Article · Oct 2010 · Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology
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    ABSTRACT: Ligand-gated calcium channels have been reported to be involved in the pathogenesis of inflammatory bowel disease. One family member, transient receptor potential vanilloid 4 (TRPV4), is activated by arachidonic acid derivatives that might be released on inflammation, yet its role in gastrointestinal inflammation has not been characterized. We investigated whether TRPV4 activation participates in intestinal inflammation and its expression and functions in the gastrointestinal tract. TRPV4 expression was studied in human colon samples, human intestinal epithelial cell lines (Caco-2 and T84), and inflamed colons of mice. Calcium mobilization and cytokine release were analyzed in intestinal epithelial cells exposed to the selective TRPV4 agonist 4α-phorbol-12,13-didecanoate (4αPDD). Mice were killed 3, 6, or 24 hours after intracolonic administration of 4αPDD; inflammatory parameters were measured in their colon tissues, and paracellular colonic permeability was measured by the passage of (51)Cr-EDTA from the colon lumen to the blood. High levels of TRPV4 were detected in Caco-2 cells and in epithelial cells of human colon tissue samples; its expression was up-regulated in colons from inflamed mice compared with noninflamed control mice. Administration of 4αPDD to Caco-2 and T84 cells caused a dose-dependent increase in intracellular calcium concentration and chemokine release. In mice, intracolonic administration of 4αPDD caused colitis to develop 3 to 6 hours later; inflammation resolved by 24 hours. Increased colonic permeability was observed in vivo 3 hours after intracolonic administration of 4αPDD. TRPV4 is expressed and functional in intestinal epithelial cells; its activation in the gastrointestinal tract causes increases in intracellular calcium concentrations, chemokine release, and colitis.
    No preview · Article · Sep 2010 · Gastroenterology
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    ABSTRACT: Krüppel-like factor (KLF) family members share a three C2H2 zinc finger DNA binding domain, and are involved in cell proliferation and differentiation control in normal as in pathological situations. Studies over the past several years support a significant role for this family of transcription factors in carcinogenesis. KLFs can both activate and repress genes that participate in cell-cycle regulation. Among them, many up-regulated genes are inhibitors of proliferation, whereas genes that promote cell proliferation are repressed. However, several studies do present KLFs as positive regulator of cell proliferation. KLFs can be deregulated in multiple cancers either by loss of heterozygosity (LOH), somatic mutation or transcriptional silencing by promoter hypermethylation. Accordingly, KLF expression was shown to mediate growth inhibition when ectopically expressed in multiple cancer-derived cell lines through the inhibition of a number of key oncogenic signaling pathways, and to revert the tumorogenic phenotype in vivo. Taken together, these observations suggest that KLFs act as tumor suppressor. However, in some occasion, KLFs could act as tumor promoters, depending on "cellular context". Thus, this review will discuss the roles and the functions of KLF family members in carcinogenesis, with a special focus on cancers from epithelial origin.
    Preview · Article · Aug 2009 · Current Genomics

  • No preview · Article · May 2009 · Gastroenterology
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    ABSTRACT: Liver transplantation improves survival of patients with end-stage (Child-Pugh stage C) alcoholic cirrhosis, but its benefit for patients with stage B disease is uncertain. To compare the outcomes of patients with Child-Pugh stage B alcoholic cirrhosis who are immediately listed for liver transplantation with those of patients assigned to standard treatment with delay of transplantation until progression to stage C disease. Randomized, controlled trial. 13 liver transplantation programs in France. 120 patients with Child-Pugh stage B alcoholic cirrhosis and no viral hepatitis, cancer, or contraindication to transplantation. Patients were randomly assigned to immediate listing for liver transplantation (60 patients) or standard care (60 patients). Overall and cancer-free survival over 5 years. Sixty-eight percent of patients assigned to immediate listing for liver transplantation and 25% of those assigned to standard care received a liver transplant. All-cause death and cirrhosis-related death did not statistically differ between the 2 groups: 5-year survival was 58% (95% CI, 43% to 70%) for those assigned to immediate listing versus 69% (CI, 54% to 80%) for those assigned to standard care. In multivariate analysis, independent predictors of long-term survival were absence of ongoing alcohol consumption (hazard ratio, 7.604 [CI, 2.395 to 24.154]), recovery from Child-Pugh stage C (hazard ratio, 7.633 [CI, 2.392 to 24.390]), and baseline Child-Pugh score less than 8 (hazard ratio, 2.664 [CI, 1.052 to 6.746]). Immediate listing for transplantation was associated with an increased risk for extrahepatic cancer: The 5-year cancer-free survival rate was 63% (CI, 43% to 77%) for patients who were immediately listed and 94% (CI, 81% to 98%) for those who received standard care. Restriction of the study sample to alcoholic patients may limit the generalizability of results to other settings. Immediate listing for liver transplantation did not show a survival benefit compared with standard care for Child-Pugh stage B alcoholic cirrhosis. In addition, immediate listing for transplantation increased the risk for extrahepatic cancer. The French National Program for Clinical Research.
    No preview · Article · Mar 2009 · Annals of internal medicine
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    ABSTRACT: Hepatitis E virus (HEV) is considered an agent responsible for acute hepatitis that does not progress to chronic hepatitis. We identified 14 cases of acute HEV infection in three patients receiving liver transplants, nine receiving kidney transplants, and two receiving kidney and pancreas transplants. All patients were positive for serum HEV RNA. Chronic hepatitis developed in eight patients, as confirmed by persistently elevated aminotransferase levels, serum HEV RNA, and histologic features of chronic hepatitis. The time from transplantation to diagnosis was significantly shorter and the total counts of lymphocytes and of CD2, CD3, and CD4 T cells were significantly lower in patients in whom chronic disease developed.
    Preview · Article · Mar 2008 · New England Journal of Medicine

Publication Stats

2k Citations
407.04 Total Impact Points

Institutions

  • 2007-2015
    • Centre Hospitalier Universitaire de Toulouse
      • Service deGastro-Entérologie et Hépatologie
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 2010-2012
    • University of Toulouse
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 1999-2012
    • Paul Sabatier University - Toulouse III
      • Centre de Physiopathologie de Toulouse Purpan - UM 98 (UMRS 1043 / UMR 5282) - CPTP
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 2011
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
  • 2009
    • French Institute of Health and Medical Research
      • Cancer Research Center of Toulouse
      Lutetia Parisorum, Île-de-France, France