PubMed Health⌕ Search

Biomedical subjects

Sébastien Dharancy

Publications and source records attributed to Sébastien Dharancy.

17 recordsLinked to original sources
PubMed2006

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

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), alpha fetoprotein level (< 200, 200 to 2000, or > 2000; P < 0.0001), gamma-GT activity (N, N to 2N or > 2N; P = 0.02), the number of nodules (1, 2-3 or > 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), bi-lobar 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 recurrence, and confirms the prognostic value of tumor differentiation.

Analysis of Variance↗
PubMed2006

Conversion to sirolimus: a useful strategy for recalcitrant cutaneous viral warts in liver transplant recipient.

Dermatological complications following transplantation are very common and the majority of immunosuppressed transplant recipients develop some to many warts due to human papillomavirus (HPV) infection. In the setting of immunosuppression, therapeutic management may be disappointing because of the extent of the lesions in patients unable to develop a sufficient immune response directed against HPV. We report here a case of a young liver transplant recipient who developed diffuse recalcitrant HPV-induced warts leading to an impairment of her quality of life. Taking into account the antiproliferative and cytostatic properties of the target-of-rapamycin (TOR) inhibitors, a new class of immunosuppressive drug, we significantly modified the immunosuppressive regimen. Conversion to sirolimus was followed by a rapid improvement of cutaneous state suggesting that this strategy may be useful for recalcitrant cutaneous viral warts in transplant recipient.

Adolescent↗
PubMed2006

Extensive portal vein thrombosis related to abdominal trauma.

Abdominal trauma is a classic but very rare cause of portal vein thrombosis. We report the case of a patient with portal vein thrombosis and cavernoma associated with portal hypertension. Anamnesis identified a serious thoraco-abdominal trauma related to a bicycle accident 6 months before. Biological screening identified an inherited heterozygous G20210A factor II gene mutation which supports a recent notion that portal vein thrombosis most often occurs when both local and systemic aetiological factors are combined.

Abdominal Injuries↗
PubMed2006

The evolution of severe steatosis after bariatric surgery is related to insulin resistance.

BACKGROUND & AIMS: In severely obese patients, factors implicated in the evolution of severe steatosis after bariatric surgery remain unresolved. Our aim was to determine whether insulin resistance (IR) influences the histologic effects induced by bariatric surgery. METHODS: We prospectively included 185 severely obese patients (body mass index >/=35 kg/m(2)) referred for bariatric surgery. The evolution of IR (IR index = 1/quantitative insulin sensitivity check index) and liver injury with consecutive biopsy was concomitantly assessed before and 1 year after surgery. RESULTS: At preoperative biopsy, 27% of severely obese patients disclosed severe steatosis (>/=60%). The alanine aminotransferase (P = .01) and IR indexes (P = .04) were independent predictive factors of severe steatosis at baseline. One year after surgery, surgical treatment induced a decrease in body mass index (9.5 kg/m(2); P < .0001), steatosis score (8.5%; P < .0001), and IR index (0.29; P < .0001). The preoperative IR index (P = .01) and preoperative steatosis (P = .006) were independent predictive factors in the persistence of severe steatosis after surgery. Moderate or severe steatosis was more frequently observed in patients who had conserved a higher IR index after surgery than in patients who had improved their IR index (44% vs 20.2%; P = .04). CONCLUSIONS: IR was independently associated with severe steatosis and predicted its persistence after surgery. The amelioration of IR after surgery is associated with a decrease in the amount of fat. Taken together, the results of this prospective study in severely obese patients demonstrate that severe steatosis and its evolution after surgery are intimately connected with IR.

Adult↗
PubMed2005

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

AIM: To elucidate the role of the peroxisome proliferator-activated receptor alpha (PPARalpha) and its target gene carnitine palmitoyl acyl-CoA transferase 1A (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. PPARalpha 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-PPARalpha antibody, then with a swine anti-rabbit IgG conjugated to horseradish peroxidase for PPARalpha. Protein bands were revealed by an enhanced chemiluminescence reaction for PPARalpha. For immunohistochemical staining of PPARalpha, sections were incubated with the primary goat polyclonal antibody directed against PPARalpha at room temperature. RESULTS: Real-time PCR indicated that the PPARalpha 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 PPARalpha 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 PPARalpha 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 PPARalpha mRNA levels were significantly lower than that in the controls. CONCLUSION: The impaired intrahepatic PPARalpha expression is associated with the pathogenic mechanism in hepatic injury during chronic HCV infection. HCV infection reduced the expression of PPARalpha and CPT1A at the level of not only mRNAs but also proteins. PPARalpha plays an important role in the pathogenesis of chronic HCV infection, but the impaired function of this nuclear receptor in HCV infection needs further studies.

Carnitine O-Palmitoyltransferase↗
PubMed2005

The frameshift mutation in Nod2 results in unresponsiveness not only to Nod2- but also Nod1-activating peptidoglycan agonists.

NOD2/CARD15 is the first characterized susceptibility gene in Crohn disease. The Nod2 1007fs (Nod2fs) frameshift mutation is the most prevalent in Crohn disease patients. Muramyl dipeptide from bacterial peptidoglycan is the minimal motif detected by Nod2 but not by Nod2fs. Here we investigated the response of human peripheral blood mononuclear cells (PBMCs) from Crohn disease patients not only to muramyl dipeptide but also to several other muramyl peptides. Most unexpectedly, we observed that patients homozygous for the Nod2fs mutation were totally unresponsive to MurNAc-L-Ala-D-Glu-meso-diaminopimelic acid (DAP) (M-Tri(DAP)), the specific agonist of Nod1, and to Gram-negative bacterial peptidoglycan. In contrast, PBMCs from a patient homozygous for the Nod2 R702W mutation, also associated with Crohn disease, displayed normal response to Gram-negative bacterial peptidoglycan. In addition, the blockage of the Nod1/M-Tri(DAP) pathway could be partially overcome by co-stimulation with the Toll-like receptors agonists lipoteichoic acid or lipopolysaccharide. Investigation into the mechanism of this finding revealed that Nod2fs did not act as a dominant-negative molecule for the Nod1/M-Tri(DAP) pathway, implying that the blockage is dependent upon the expression or activity of other factors. We demonstrated that PBMCs from Nod2fs patients express high levels of the peptidoglycan recognition protein S, a secreted protein known to interact with muramyl peptides. We proposed that through a scavenger function, peptidoglycan recognition protein S may dampen M-Tri(DAP)-dependent responses in Nod2fs patients. Together, our results identified a cross-talk between the Nod1 and Nod2 pathways and suggested that down-regulation of Nod1/M-Tri(DAP) pathway may be associated with Crohn disease.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed2005

Impaired expression of the peroxisome proliferator-activated receptor alpha during hepatitis C virus infection.

BACKGROUND AND AIMS: Liver inflammation, fibrosis, and dyslipidemia are common features in patients with chronic hepatitis C virus (HCV) infection. Because peroxisome proliferator-activated receptor alpha (PPARalpha) is highly expressed in the liver and is involved in the regulation of lipid metabolism and inflammation, we sought to determine whether HCV infection may locally impair PPARalpha expression and activity. METHODS: PPARalpha expression was investigated in liver biopsy specimens of 86 untreated patients with HCV infection and controls, by using real-time polymerase chain reaction (PCR), Western blot analysis, and immunohistochemistry. PPARalpha activity was assessed by quantification of the key gene target carnitine palmitoyl acyl-CoA transferase 1 (CPT1A) messenger RNA (mRNA). The influence of HCV core protein on PPARalpha mRNA expression was analyzed in vitro by real-time PCR in HCV core-expressing HepG2 cells activated with the PPARalpha ligand fenofibric acid. RESULTS: Hepatic concentrations of PPARalpha and CPT1A expressed by hepatocytes were impaired profoundly in the livers of untreated patients with HCV infection compared with controls. A mean decrease of 85% in PPARalpha mRNA expression paralleled with a lack of CPT1A mRNA induction also were observed in HCV core-expressing HepG2 cells compared with controls. CONCLUSIONS: HCV infection is related to altered expression and function of the anti-inflammatory nuclear receptor PPARalpha. These results identify hepatic PPARalpha as one mechanism underlying the pathogenesis of HCV infection, and as a new therapeutic target in traditional treatment of HCV-induced liver injury.

Biopsy↗
PubMed2004

A double-blind randomized controlled trial of infliximab associated with prednisolone in acute alcoholic hepatitis.

Tumor necrosis factor-alpha (TNF-alpha) may contribute to the progression of acute alcoholic hepatitis (AAH). The aim of this study was to evaluate the efficacy of an association of infliximab and prednisolone at reducing the 2-month mortality rate among patients with severe AAH. Patients with severe AAH (Maddrey score >/=32) were randomly assigned to group A receiving intravenous infusions of infliximab (10 mg/kg) in weeks 0, 2, and 4; or group B receiving a placebo at the same times. All patients received prednisolone (40 mg/day) for 28 days. Blood neutrophil functional capacities were monitored over 28 days. After randomization of 36 patients, seven patients from group A and three from group B died within 2 months. The probability of being dead at 2 months was higher (not significant [NS]) in group A (39% +/- 11%) than in group B (18% +/- 9%). The study was stopped by the follow-up committee and the sponsor (Assistance Publique-Hôpitaux de Paris). The frequency of severe infections within 2 months was higher in group A than in group B (P <.002). This difference was potentially related to a significantly lower ex vivo stimulation capacity of neutrophils. There were no differences between the two groups in terms of Maddrey scores at any time point. In conclusion, three infusions of 10 mg/kg of infliximab in association with prednisolone may be harmful in patients with severe AAH because of the high prevalence of severe infections.

Acute Disease↗
PubMed2003

Primary lymphoma of the liver: clinical-pathological features and relationship with HCV infection in French patients.

Primary lymphoma of the liver (PLL) is rare. In some cases, the hepatic lymphoma has been diagnosed in patients who were infected by the hepatitis C virus (HCV). It has been suggested that HCV plays a role in the pathogenesis of lymphoma. The aim of our multicentric retrospective study was to assess the characteristics of PLL and to determine the prevalence of HCV infection in PLL. Thirty-one immunocompetent patients (anti-human immunodeficiency virus, anti-human T-cell leukemia/lymphoma virus negative, no history of allograft) with PLL fulfilled the entire selection criteria. The liver biopsy specimens were reassessed by the same pathologist. The non-Hodgkin's lymphomas were classified according to the World Health Organization classification. Blood samples were tested in 28 patients for antibodies to HCV, and HCV RNA was detected by reverse transcription polymerase chain reaction. In the majority of cases, the clinical, biologic, and radiologic data were nonspecific. Twenty-seven of 31 patients presented a B-cell lymphoma corresponding to the centroblastic morphologic variant of a diffuse, large B-cell lymphoma (22 cases), a Burkitt's lymphoma (1 case), an extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type (3 cases), and unclassified, small B-cell lymphoma (1 case). The 4 other cases were T-cell lymphomas. The prevalence of HCV infection was 21% (6 of 28 cases). All of these patients were positive for HCV RNA by polymerase chain reaction in blood. Most of the HCV-infected patients presented a high-grade, B-cell type lymphoma. In conclusion, our study confirms the rarity of PLL and demonstrates an increased prevalence of HCV infection.

Adult↗
PubMed2002

Role of peroxisome proliferator-activated receptor gamma and retinoid X receptor heterodimer in hepatogastroenterological diseases.

The peroxisome proliferator-activated receptor gamma (PPARgamma) and its partner the retinoid X receptor (RXR) are two nuclear receptors that are expressed mainly in adipose tissue and which have a role in lipid metabolism and insulin sensitisation. New sites of PPARgamma/RXR expression have been described, especially in the intestinal tract, pancreas, and liver. Concomitantly, new functions have been attributed to this heterodimer in regulation of inflammation, by its inhibition of nuclear factor (NF)-kappaB and via stress-kinase pathways. These new sites and functions of PPARgamma/RXR have led to novel ideas about pathophysiology of different inflammatory digestive diseases and to development of innovative treatment strategies with PPARgamma activators.

Adipose Tissue↗
PubMedDate not supplied

[Membranous glomerulonephritis complicating hepatocellular carcinoma].

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.

Aged↗