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Hepatitis C virus infection down-regulates the expression of peroxisome proliferator-activated receptor a and carnitine palmitoyl acyl-CoA transferase 1A

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World Journal of Gastroenterology 2005年第48期11卷 7591-7596页

作者： Yang Cheng sébastien dharancy Mathilde Malapel Pierre Desreumaux Equipe mixte INsERM 0114

AIM： To elucidate the role of the peroxisome proliferator-activated receptor α （PPARα） and its target gene camitine palmitoyl acyl-CoA transferase 2A （CPT1A） in the pathogenesis of hepatitis C virus （HCV） infection.METHODs： Liver samples were collected from the patients with chronic HCV infection and controls. HepG2 cells were transfected with vector pEF352neo carrying. Two independent clones （clone N3 and N4） stably expressing HCV core protein were analyzed. Total RNA was extracted from cells and liver tissues. PPARα and CPT1A mRNAs were quantified by real-time polymerase chain reaction （PCR） using sYBR Green Master. Total extracted proteins were separated by polyacrylamide gel electrophoresis, and electroblotted. Membranes were incubated with the anti-PPARα antibody, then with a swine anti-rabbit IgG conjugated to horseradish peroxidase for PPARα. Protein bands were revealed by an enhanced chemiluminescence reaction for PPARα. For immunohistochemical staining of PPARα, sections were incubated with the primary goat polyclonal antibody directed against PPARα at room temperature.REsULTs： Real-time PCR indicated that the PPARα level and expression level of CPT1A gene in hepatitis C patients lowered significantly as compared with the controls （1.8±2.8 vs 13±3.4, P = 0.0002; 1.1±1.5 vs 7.4±1, P = 0.004）. Western blot results showed that the level of PPARα protein in the livers of hepatitis C patients was lower than that in controls （2.3±0.3 vs 3.6±0.2, P = 0.009）. The immunohistochemical staining results in chronic hepatitis C patients indicated a decrease in PPARα staining in hepatocytes compared with those in the control livers. The in vitro studies found that in the N3 and N4 colon stably expressing HCV core protein, the PPARα mRNA levels were significantly lower than that in the controls.CONCLUsION： The impaired intrahepatic PPARα expression is associated with the pathogenic mechanism in hepatic injury during chronic HCV infection. HCV infection reduced the ex

关键词： Hepatitis C virus Infection PPARα CPT1A

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Role of immunosuppression and tumor differentiation in predicting recurrence after liver transplantation for hepatocellular carcinoma: A multicenter study of 412 patients

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World Journal of Gastroenterology 2006年第45期12卷 7319-7325页

作者： Thomas Decaens Franoise Roudot-Thoraval solange Bresson-Hadni Carole Meyer Jean Gugenheim Francois Durand Pierre-Henri Bernard Olivier Boillot Philippe Compagnon Yvon Calmus Jean Hardwigsen Christian Ducerf Georges Philippe Pageaux sébastien dharancy Olivier Chazouillères Daniel Cherqui Christophe Duvoux service d'Hépatologie et de Gastroentérologie AP-HP Hpital Henri Mondor Créteil Unité INSERM 581 France Département de santé Publique AP-HP Hpital Henri Mondor Créteil France service d’Hépatologie Hpital Jean Minjoz Besanon France service de Transplantation Hpital HautefeuilleStrasbourg France service de Chirurgie Digestive Hpital L’Ar-chet 2 Nice France service d’Hépatologie AP-HP Hpital Beau-jon Clichy France service d’Hépatologie et de Gastroentéro-logie H?pital Pellegrin Bordeaux France service de Chirurgie Digestive Hpital Edouard Herriot Lyon France service de Chirurgie Digestive Hpital Ponchaillou Rennes France service de Chirurgie Digestive AP-HP HpitalCochin Paris France service de Chirurgie Digestive Hpital laConception Marseille France service de Chirurgie Digestive Hpital de laCroix Rousse Lyon France Fédération Médico-Chirurgicale deMaladies de l’Appareil Digestif Hpital Saint-Eloi MontpellierFrance service d’Hépatologie et de Gastroentérologie H?pital Claude Huriez Lille France service d’Hépatologie AP-HP Hpital SAntoine Paris France service de Chirurgie Générale et Digestive APHP Hopital Henri Mondor Créteil France

AIM： To assess pre-orthotopic liver transplantation （OLT） factors that could be evaluated pre-operatively or controlled post-operatively associated with hepatocellular carcinoma （HCC） recurrence and disease-free survival after liver transplantation （LT）.METHODs： Four hundred and twelve patients transplanted for HCC between 1988 and 1998 in 14 French centers, who survived the postoperative period were studied. Kaplan Meier estimates were calculated for 24 variables potentially associated with recurrence of HCC. Uni- and multivariate analyses were conducted to identify independent predictors of recurrence. REsULTs： Overall 5-year disease-free survival was 57.1%. By univariate analysis, variables associated with disease-free survival were： presence of cirrhosis （P = 0.001）, etiology of liver disease （P = 0.03）, α fetoprotein level （〈 200, 200 to 2000, or 〉 2000; P 〈 0.0001）, y-GT activity （N, N to 2N or 〉 2N; P = 0.02）, the number of nodules （1, 2-3 or ≥ 4; P = 0.02）, maximal diameter of the largest nodule （〈 3 cm, 3 to 5 cm or 〉 5 cm; P 〈 0.0001）, the sum of the diameter of the nodules （〈 3 cm, 3 to 5 cm, 5 to 10 cm or 〉10 cm; P 〈 0.0001）, bilobar location （P = 0.01）, preoperative portal thrombosis （P 〈 0.0001）, peri-operative treatment of the tumor （P = 0.002） and chemoembolization （P = 0.03）, tumor differentiation （P = 0.01）, initial type of calcineurin inhibitor （P = 0.003）, the use of antilymphocyte antibodies （P = 0.02）, rejection episodes （P = 0.003） and period of LT （P 〈 0.0001）. By multivariate analysis, 6 variables were independently associated with HCC recurrence： maximal diameter of the largest nodule （P 〈 0.0001）, time of LT （P 〈 0.0001）, tumor differentiation （P 〈 0.0001）, use of anti-lymphocyte antibody （ATG） or anti-CD3 antibody （OKT3）（P = 0.005）, preoperative portal thrombosis （P = 0.06） and the number of nodules （P = 0.06）. CONCLUsION： This study identifies immunosuppression, through the use of ATG or OKT3, as a predictive factor of tumor recur

关键词： Immunosuppression Hepatocellular carcinoma Tumor differentiation Liver transplantation

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膜性肾小球肾炎伴发肝细胞性肝癌(法)

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世界核心医学期刊文摘（胃肠病学分册） 2005年第1期1卷 28-29页

作者： Texier F. dharancy s. Provot F. s.dharancy 樊菁 serv.Malad. Appareil Digestif/Nutr. Hpital Claude HuriezCHU Lille 59037 Lille Cedex France

We report the case of a 65-year-old man with advanced hepatocellular carcinoma related to alcoholic cirrhosis who was hospitalised for oliguric renal failure. Investigations showed a severe nephrotic syndrome related to paraneoplastic membranous glomerulonephritis. The patient s course was temporarily stabilized with loop diuretics and dialysis but the patient died of hemoperitoneum from a ruptured tumor.

关键词：膜性肾小球肾炎肝细胞性肝癌肾病综合征肾功能衰竭酒精性肝硬化袢利尿剂肿瘤破裂男性病例

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