Insecticides cytotoxicity and CYP1A1 induction in primary human and rat hepatocytes cultures

With the increasing demand for insecticide products, the question of their safety has become one of the serious world public health concerns. The capability of compounds belonging to the major insecticide families [such as chlorinated hydrocarbons (DDT), carbamates (carbaryl: CBR), organophosphorus compounds (malathion, tetrachlorvinfos: MAL, TCV), pyrethroids (cypermethrin: CPR) and benzoylurea (diflubenzuron: DFU)] in inducing CYP1 Al in rat and human hepatocyte cultures has been tested. Cells were treated during 3 days with six non-toxic increasing doses of insecticides and CYP1A1 expression was assessed by ethoxyresorufin O-deethylase (EROD) activity and by Northern blots. A strong and dose-dependent induction was observed with TCV and DFU, both in human (approx. five- and sevenfold over control, respectively) and in rat hepatocytes (approx. sevenfold). However, EROD induction and CYP/A1 mRNA levels were correlated for DFU but not for TCV, suggesting different regulation mechanisms for PCYP1A1 gene expression by the two compounds. CBR and CPR exerted less induction in both cell types (approx. 2.5-fold induction compared with approximately 16-fold for 3-methylcholanthrene), whereas DDT and MAL showed no action on human hepatocytes but decreased EROD activity in rat cells. Finally, cytotoxicity studies performed using the MTT and the neutral red tests demonstrated significant differences between insecticides

Insecticide cytotoxicity and CYP1A1/2 induction in primary human and rat hepatocyte cultures

International audienc

Comparative study of CYP1A1 induction by 3-methylcholanthrene in various human hepatic and epidermal cell types

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The presence of spontaneous portosystemic shunts increases the risk of ă complications after transjugular intrahepatic portosystemic shunt (TIPS) ă placement

International audiencePurpose: The goal of this study was to identify clinical and imaging ă variables that are associated with an unfavorable outcome during the 30 ă days following transjugular intrahepatic portosystemic shunt (TIPS) ă placement. ă Material and methods: Fifty-four consecutive patients with liver ă cirrhosis (Child-Pugh 6-13, Model for End-stage Liver Disease 7-26) ă underwent TIPS placement for refractory ascites (n = 25), recurrent or ă uncontrolled variceal bleeding (n = 23) or both (n = 6). Clinical, ă biological and imaging variables including type of stent (covered n = ă 40; bare-stent n = 14), presence of spontaneous portosystemic shunt (n = ă 31), and variations in portosystemic pressure gradient were recorded. ă Early severe complication was defined as the occurrence of overt hepatic ă encephalopathy or death within the 30 days following TIPS placement. ă Results: Sixteen patients (30%) presented with early severe ă complication after TIPS placement. Child-Pugh score was independently ă associated with complication (HR = 1.52, P < 0.001). Among the imaging ă variables, opacification of spontaneous portosystemic shunt during TIPS ă placement but before its creation was associated with an increased risk ă of early complication (P = 0.04). The other imaging variables were not ă associated with occurrence of complication. ă Conclusion: Identification of spontaneous portosystemic shunt during ă TIPS placement reflects the presence of varices and is associated with ă an increased risk of early severe complication

Detection of rare hepatitis C viruses of subtype 4r in Southeastern France

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Supplementary Material for: Hepatitis C Virus of Subtype 2l in Marseille, Southeastern France

<p>The rate of eradication of chronic hepatitis C considerably increases with direct-acting antiviral agents, particularly hepatitis C virus (HCV) polymerase inhibitors. While implementing full-length HCV NS5B polymerase sequencing in our clinical microbiology laboratory, we identified atypical HCV sequences, classified as subtype 2l, from 2 patients. HCV-2l NS5B polymerase sequences were detected from 5 and 14 additional patients by screening our laboratory hepatitis virus sequence database and the NCBI GenBank sequence database. Phylogenetic analyses show unambiguously that all HCV-2l sequences are clustered apart from HCV 2 non-l sequences, which compose a second cluster. Mean (±SD) nucleotide identity between near full-length NS5B fragments of subtype 2l was 93.4 ± 0.8% (range: 92.4-95.1). Of note, all HCV-2l sequences obtained in our laboratory and in other centers were from serum samples collected in France. Analysis of the HCV-2l NS5B polymerase amino acid sequences at 30 positions critical for interaction with or resistance to HCV polymerase inhibitors showed specific patterns.</p

P0804 : Efficacy of sofosbuvir-based treatment regimens in HIV/HCV co-infected patients after liver transplantation: The ANRS CO23 CUPILT study

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European collaborative study on factors influencing outcome after liver transplantation for hepatitis C

Background & Aims: Liver transplantation for hepatitis C virus (HCV)-related liver disease is characterized by frequent graft infection by HCV. The prognosis and risk factors for morbidity and mortality in this condition were determined. Methods: A retrospective study of 652 consecutive anti-HCV-positive patients undergoing liver transplantation between 1984 and 1995 in 15 European centers was conducted; 102 patients coinfected with hepatitis B virus (HBV) received immunoglobulin prophylaxis for antibody to hepatitis B surface antigen. Results: Overall, 5-year survival was 72%. Five-year actuarial rates of hepatitis and cirrhosis were 80% and 10%. Genotypes 1b, 1a, and 2 were detected in 214 (80%), 24 (9%), and 24 (9%) of 268 patients analyzed. The only discriminant factor for patient or graft survival was hepatocellular carcinoma as primary indication. Independent risk factors for recurrent hepatitis included the absence of HBV coinfection before transplantation (relative risk [RR], 1.7; 95% confidence interval [CI], 1.2-2.6; P = 0.005), genotype Ib (RR, 2; 95% CI, 1.3-2.9; P = 0.01), and age > 49 years (RR, 1.4; 95% CI, 1.1-1.8; P = 0.01). Conclusions: The results of transplantation for HCV-related disease are compromised by a significant risk of cirrhosis, although 5-year survival is satisfactory. Genotype 1b, age, and absence of pretransplantation coinfection by HBV are risk factors for recurrent HCV

LP05 : Daclatasvir plus sofosbuvir with or without ribavirin in patients with HCV genotype 3 infection: Interim analysis of a french multicenter compassionate use program

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