Etude épidemiologique du syndrome de chevauchement de la cirrhose biliaire primitive et de l'hépatite auto-immune (A propos d'une série de115 cas)

REIMS-BU Santé (514542104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Toxicité intestinale de l aspirine à faible dose et des autres traitements antithrombotiques: étude rétrospective par vidéo-capsule chez des patients atteints d anémie

REIMS-BU Santé (514542104) / SudocSudocFranceF

Impact des facteurs métaboliques sur le risque de développement de varices oesophagiennes chez les patients cirrhotiques alcooliques

REIMS-BU Santé (514542104) / SudocSudocFranceF

Evaluation de la fibrose hépatique chez les patients atteints d' hépatite C chronique : intérêt de l'analyse du sérum par spectroscopie infrarouge

REIMS-BU Santé (514542104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Evaluation de nouvelles associations d'agents anti-néoplasiques dans le traitement des cancers gastriques

L'@objectif de notre thèse était de présenter les résultats de nos travaux qui avaient pour but l'évaluation de nouvelles associations d'agents anti-néoplasiques dans le traitement adjuvant et palliatif des cancers gastriques. Après résection à visée curative de cancers gastriques à haut risque de récidive, un essai contrôlé randomisé multicentrique de phase III a montré une réduction du risque relatif de 26% pour les décès (p = 0,06) et de 30% pour les récidives (p = 0,03) chez les patients recevant la chimiothérapie adjuvante par 5FU continu et cisplatine (FUP). Un ratio ganglions envahis sur ganglions examinés de plus de 30% était le principal facteur pronostique péjoratif en analyse multivariée (p=0,0001). Une analyse rétrospective a montré l'excellente tolérance du schéma post-opératoire de chimiothérapie acide folinique et 5FU bolus puis continu (LV5FU2) associé à une radiothérapie de 45 Gy. Dans une étude multicentrique randomisée de phase II incluant des cancers métastatiques, la chimiothérapie par 5FU bolus, acide-L-folinique et cisplatine (FUFOL-P) était aussi active que l'association FUP avec réduction du risque de mucite sévère. Dans un second essai randomisé multicentrique de phase II, les taux de réponse objective étaient 40% pour LV5FU2-irinotécan, 27% pour LV5FU2-cisplatine et 13% pour LV5FU2, pour des survies médianes respectives de 11,3 mois, 9,5 mois et 6,8 mois. Le profil de tolérance était favorable au LV5FU2-irinotécan par rapport au LV5FU2-cisplatine sans détérioration des scores de qualité de vie dans l'analyse longitudinale. Suite à ces résultats, l'association LV5FU2-irinotécan va être évaluée en phase III en indication adjuvante et palliative.REIMS-BU Santé (514542104) / SudocSudocFranceF

EFFET PROTECTEUR DE L'APPENDICECTOMIE CONTRE LA RECTOCOLITE HEMORRAGIQUE (ETUDE CAS-TEMOINS)

REIMS-BU Santé (514542104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Dietary components modulate the risk of hepatocellular carcinoma in cirrhotic patients

Eighty percent of hepatocellular carcinoma (HCC) cases occur after cirrhosis from various etiologies. The association between diet and cancer is well accepted, but the links with cirrhosis progression and HCC risk have been poorly investigated. However, we hypothesized that diet could be a modifiable preventive factor for HCC. Thus, the aim of our study was to explore the relationships between dietary factors and the risk of HCC in a population of cirrhotic patients. A total of 582 cirrhotic patients were studied: 401 without HCC (controls) and 181 with HCC (cases). These patients were recruited between 2008 and 2012 for the "CiRCE" case-control study conducted in six French university hospitals. Information about the consumption of 208 food items and 23 nutrients were collected through a diet history questionnaire. Unconditional multivariate logistic regressions were performed for each residual food group and nutrients in tertiles. HCC patients were more often men, diabetic and older than controls. After adjustment, a significant positive association was found between HCC risk and carbonated beverages (ORTertile3vsTertile1=2.44 [1.17-5.09] p-trend=0.021), total cereals (ORT3vsT1=1.87 [1.09-3.22] p-trend=0.035), processed meat (ORT3vsT1=1.97 [1.14-3.41] p-trend=0.028) and sodium (ORT3vsT1=2.00 [1.14-3.53] p-trend=0.043). Conversely, the consumption of fiber (ORT3vsT1=0.49 [0.28-0.86] p-trend=0.012), vitamin E (ORT3vsT1=0.52 [0.30-0.89] p-trend=0.017), vitamin B9 (folate and folic acid) (ORT3vsT1=0.56 [0.33-0.95] p-trend=0.036), manganese (ORT3vsT1=0.56 [0.32-0.97] p-trend=0.038) and potassium (ORT3vsT1=0.44 [0.25-0.76] p-trend=0.004) were significantly lower in HCC patients compared with cirrhotic controls. Although these findings must be confirmed in prospective studies, using dietary patterns or biological parameters, they suggest that certain dietary components may modulate HCC risk in cirrhotic patients

Immediate listing for liver transplantation versus standard care for Child-Pugh stage B alcoholic cirrhosis: a randomized trial.

International audienceBACKGROUND: 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. OBJECTIVE: 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. DESIGN: Randomized, controlled trial. SETTING: 13 liver transplantation programs in France. PATIENTS: 120 patients with Child-Pugh stage B alcoholic cirrhosis and no viral hepatitis, cancer, or contraindication to transplantation. INTERVENTIONS: Patients were randomly assigned to immediate listing for liver transplantation (60 patients) or standard care (60 patients). MEASUREMENTS: Overall and cancer-free survival over 5 years. RESULTS: 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. LIMITATION: Restriction of the study sample to alcoholic patients may limit the generalizability of results to other settings. CONCLUSION: 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. FUNDING: The French National Program for Clinical Research

BRIP1 coding variants are associated with a high risk of hepatocellular carcinoma occurrence in patients with HCV- or HBV-related liver disease

IF 5.008International audienceThe molecular mechanisms of hepatocellular carcinoma (HCC) carcinogenesis are still not fully understood. DNA repair defects may influence HCC risk. The aim of the study was to look for potential genetic variants of DNA repair genes associated with HCC risk among patients with alcohol- or viral-induced liver disease. We performed four case-control studies on 2,006 European- (Derivation#1 and #2 studies) and African-ancestry (Validation#1 and #2 studies) patients originating from several cohorts in order to assess the association between genetic variants on DNA repair genes and HCC risk using a custom array encompassing 94 genes. In the Derivation#1 study, the BRIP1 locus reached array-wide significance (Chi-squared SV-Perm, P=5.00×10-4) among the 253 haplotype blocks tested for their association with HCC risk, in patients with viral cirrhosis but not among those with alcoholic cirrhosis. The BRIP1 haplotype block included three exonic variants (rs4986763, rs4986764, rs4986765). The BRIP1 'AAA' haplotype was significantly associated with an increased HCC risk [odds ratio (OR), 2.01 (1.19-3.39); false discovery rate (FDR)-P=1.31×10-2]. In the Derivation#2 study, results were confirmed for the BRIP1 'GGG' haplotype [OR, 0.53 (0.36-0.79); FDR-P=3.90×10-3]. In both Validation#1 and #2 studies, BRIP1 'AAA' haplotype was significantly associated with an increased risk of HCC [OR, 1.71 (1.09-2.68); FDR-P=7.30×10-2; and OR, 6.45 (4.17-9.99); FDR-P=2.33×10-19, respectively]. Association between the BRIP1 locus and HCC risk suggests that impaired DNA mismatch repair might play a role in liver carcinogenesis, among patients with HCV- or HBV-related liver disease