Background: Liver transplantation (LT) remains a potentially haemorrhagic procedure whose perioperative bleeding and transfusion could be better monitored using point-of-care devices. Quantra® is a device based on sonorheometry to assess whole blood clot formation. Our aims were to describe Quantra® parameters during LT and to study their correlations with standard laboratory parameters, and to determine Quantra® cut-off values for thrombocytopenia, hypofibrinogenemia and coagulation factors’ deficit. Methods: In 34 patients undergoing LT, blood samples were collected before surgical incision, 15 min after the beginning of the anhepatic phase, and 15 min after arterial revascularization of the graft. Results: Clotting time (CT) was well correlated with prothrombin (PT) ratio and activated partial thromboplastin time (aPTT) ratio. Platelet contribution to clot stiffness (PCS) was correlated with platelets (ρ = 0.82, p < 0.001) and fibrinogen contribution clot stiffness (FCS) with fibrinogen (Fg) (ρ = 0.74, p < 0.001). CT predicted a PT ratio < 30% with an area under the curve (AUC) of 0.93 (95% CI 0.87–0.98; p < 0.001). PCS predicted a platelet count < 50 G/L with an AUC of 0.87 (95% CI 0.76–0.98, p < 0.001). FCS predicted a Fg < 1.0, 1.2 or 1.5 g/L, with an AUC of 0.86 (95% CI 0.77–094, p < 0.001), 0.82 (95% CI 0.74–0.91, p < 0.001) and 0.88 (95% CI 0.82–0.95, p < 0.001), respectively. Conclusion: Quantra® provides a rapid assessment of haemostasis during LT.

The use of predictive biomarkers in the diagnosis and prediction of the efficacy of targeted therapies for the individualized management of patients is generally based on the use of in vitro medical diagnosis devices that are now covered by the guidelines 90/385/EEC, 93/42/EEC and 98/42/EEC. On 25 May 2017, the European Parliament and Council Regulations 2017/745 and 2017/746 of 5 April 2017, related to medical devices and in vitro medical diagnosis devices, respectively, were published, disrupting years of practices based on European directives. They tend to bring the in vitro diagnosis in Europe closer to the American regulation in order to improve the use of safety diagnosis tests, while the United States have been changing their practices in the face of biomedical, technological and digital evolutions. We will describe the different regulations of diagnostic tests and discuss their applications in the field of oncology.

Circadian rhythms have been related to psychiatric diseases and regulation of dopaminergic transmission, especially in substance abusers. The relationship between them remained enigmatic and no data on the role of clock genes on cannabis dependence have been documented. We aimed at exploring the role of clock gene genotypes as potential predisposing factor to cannabis addiction, using a high throughput mass spectrometry methodology that enables the large-scale analysis of the known relevant polymorphisms of the clock genes. We have conducted a case-control study on 177 Caucasians categorizing between cannabis-addicted subjects and casual consumers based on structured interviews recorded socio-demographic data, AUDIT, Fagerström test, MINI, and medical examinations. Alcohol, opiates, and stimulants' consumption was as exclusion criteria. We report an association between several Single Nucleotide Polymorphism (SNP)s in main circadian genes SNPs, especially the gene locus HES7/PER1 on chromosome 17 and cannabis consumption as well as the development of neuropsychiatric and social disorders. This SNP's signature that may represent a meaningful risk factor in the development of cannabis dependence and its severity requires to be deeply explored in a prospective study.

La cirrhose est un problème de santé publique au niveau mondial. Le diagnostic de cirrhose sous-tend un risque accru de morbidité et de mortalité mais également de développement d’une tumeur primitive du foie, la plus fréquente étant le carcinome hépatocellulaire (CHC). Dans les pays en développement, l’hépatite virale représente le principal facteur de risque, tandis que dans les pays développés, l’épidémie d’obésité, de diabète et de stéatohépatite non alcoolique (NASH) contribue à l’augmentation observée de l’incidence du CHC. Le diagnostic précoce est crucial pour faire bénéficier les patients des traitements curatifs que sont la résection chirurgicale, l’ablation par radiofréquence et la transplantation hépatique. On recommande aux patients cirrhotiques de subir une surveillance du CHC par échographie abdominale à intervalles de 6 mois. Les algorithmes de diagnostic actuels pour le CHC reposent sur des caractéristiques radiologiques typiques dans l’imagerie par contraste dynamique, tandis que l’utilisation de l’α-fœtoprotéine (AFP) comme outil indépendant pour la surveillance du CHC n’est pas recommandée par les directives actuelles en raison de sa faible sensibilité et spécificité. D’autres bio-marqueurs sériques et des sous-classifications histo-moléculaires basées sur des signatures ou des anomalies génétiques sont prometteurs pour une amélioration de la prise en charge des patients. Cependant, ils nécessitent des évaluations cliniques plus larges pour être appliqués à la pratique clinique. Afin d’optimiser la prise en charge des patients au sein d’équipes spécialisées, l’utilisation d’un arbre décisionnel (classification BCLC, Barcelona Clinic Liver Cancer) est recommandée. Il répartit les patients atteints de CHC en 5 stades, pour déterminer le pronostic et l’attribution du traitement.

Prior studies have associated 677C-T Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with decreased enzymatic activity and modified homocysteine regulation. This study determines and compares MTHFR 677C-T distribution and examines its consequences on homocysteine metabolism and alcohol dependence in alcoholic patients classified according to the Babor and Lesch typologies. MTHFR TT genotype was more prevalent in AD patients with milder alcohol dependence (Babor type A) and with Lesch type 3, associated with depression. MTHFR TT was also associated with hyperhomocysteinemia. Determining MTHFR 677C-T genotype, folate and vitamin B12 levels could assist physicians in identifying type 3 patients and improve addictions management.

Primary liver cancer is a major public health problem, accounting for about 600,000 deaths in the world annually, with hepatocellular carcinoma (HCC) accounting for about 80% of all primary tumours in the liver and intra-hepatic cholangiocarcinoma (ICC) representing about 10-15% of the remaining primary hepatic malignancies. Incidence and mortality trends for both HCC and ICC are increasing globally, with particular concern for US and Europe, and survival rates are still very poor. Some risk factors are well-established, such as hepatitis viruses, alcohol intake and aflatoxins exposure for HCC, and infection with liver flukes and primary sclerosing cholangitis for cholangiocarcinoma (CC). However, these known etiologies do not explain the observed increased incidence of these two malignancies worldwide. Environmental carcinogens could play an underestimated role in the increased global burden of primary liver cancers. An essential tool to identify chemical and physical carcinogenic agents is long-term carcinogenicity bioassays, such as those performed by the US National Toxicology Program and the Ramazzini Institute. Although some strains of rodents are reported to be more susceptible to chemical-induced hepatocarcinogenicity, many similarities in histologic, cytological and molecular pathways are shared between humans and rodents in liver tumorigenesis, thus making long-term carcinogenicity bioassays the best available tool for identifying environmental carcinogenic agents, including those targeting the liver. Moreover, early detection of HCC and CC should provide a valuable means to decrease mortality rates in the short term, but reliable biomarkers are not yet available for clinical practice. Advanced technologies such as proteomics and in vivo imaging techniques are now available for animal cancer models. Well-designed protocols which will integrate a proteomic approach with imaging diagnostics using animal models may result in greater improvement for biomarkers development in early diagnosis of primary liver cancers. Eur. J. Oncol., 14 (3), 133150, 2009

Background: Hyperhomocysteinemia is frequently observed in alcohol-dependent subjects, in particularly in those with marked withdrawal symptoms. The common C677T transition on the methylenetetrahydrofolate reductase (MTHFR) gene influences homocysteinemia. Our objective was to study the prevalence of the MTHFR C677T polymorphism in alcohol-dependent subjects and the influence of this polymorphism on symptoms associated with alcoholism.Methods: MTHFR C677T polymorphism was determined in 93 control subjects and 242 alcohol-dependent subjects. Serum homocysteine, folate and vitamin B-12 levels together with hepatic biological parameters were determined in the control and alcohol-dependent subjects.Results: Hyperhomocysteinemia is frequently observed in alcohol-dependent subjects, particularly in those with marked withdrawal symptoms. Alcohol-dependent subjects showed a significant decrease in MTHFR 677TT prevalence (9%, 21/242) compared to controls (18%, 17/93) (P < 0.02). The relative risk estimated as an odds ratio for alcoholism in subjects with the TT genotype is 0.42 (odd ratio 95% confidence interval, 0.21-0.83). Moreover, drinkers with TT genotype presented lower values for markers of alcohol misuse (p < 0.05), better liver function tests, a lower frequency of relapses and no marked withdrawal symptoms as assessed by the Lesch typology.Conclusion: MTHFR 677TT genotype could play a protective role against alcohol dependence. Moreover, when subjects with MTHFR 677TT genotype become dependent to alcohol, they seem to constitute a subgroup of alcoholic patients with a decreased risk for developing neurotoxic withdrawal symptoms and hepatic toxicity. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Cirrhosis caused by hepatitis B virus, hepatitis C virus or chronic alcohol intake is associated with major risk. Systematic screening for HCC of asymptomatic patients with cirrhosis is needed for earlier detection of small tumors requiring treatment (liver transplantation, surgical resection, percutaneous techniques). The recommended screening strategy among cirrhotic patients is based on regular liver ultrasonography associated with serum alpha-fetoprotein (AFP) assay. As the performance of AFP is not satisfactory, additional tumoral markers are proposed (des-gamma-carboxyprothrombin, glycosylated AFP-L3 fraction). Currently, diagnosis of HCC in cirrhotic patients includes non-invasive tests (imaging after contrast administration, AFP assay); diagnostic biopsy is per-formed when imaging is limited. After treatment, tumor recurrence is assessed by regular follow-up (AFP assay and imaging). Despite the lack of accurate markers, recent developments in genomic and proteomic approaches will allow the discovery of new biomarkers for primary tumors, as well as for recurrence. This review summarizes the current state of biomarkers for screening, diagnosis and follow-up of HCC, and highlights new perspectives in the field.

Le carcinome hépatocellulaire (CHC) arrive au cinquième rang des tumeurs les plus fréquentes dans le monde. Les principaux facteurs de risque sont la cirrhose tout particulièrement liée aux virus de l'hépatite B et C et à l'alcoolisme chronique. Le dépistage systématique du CHC chez les patients cirrhotiques asymptomatiques permet de détecter précocement les tumeurs de petite taille pouvant bénéficier d'un traitement (transplantation hépatique, résection chirurgicale, traitements percutanés). Une stratégie de dépistage chez les patients atteints de cirrhose, par échographies répétées associées ou non au dosage de l'alphafoetoprotéine (AFP), est actuellement recommandée. L'utilisation de l'AFP restant insatisfaisante, certains marqueurs sont proposés en association (décarboxyprothrombine, AFP fucosylée). Le diagnostic de CHC sur cirrhose repose sur des critères non invasifs (imagerie après injection de produits de contraste, AFP sérique), l'examen anatomopathologique est réalisé quand les critères d'imagerie sont insuffisants. Après traitement, le risque de récidive tumorale impose une surveillance régulière (AFP sérique + imagerie). Bien qu'aucun marqueur suffisamment validé n'émerge encore, le développement depuis quelques années de technologies d'analyse globale du génome et du protéome devrait permettre la découverte de nouveaux marqueurs biologiques de détection précoce de la tumeur primaire et de la récidive.

Le carcinome hepatocellulaire (CHC) vient au cinquieme rang des tumeurs les plus frequentes dans le monde et son incidence tend a augmenter, en partie en raison du nombre important de sujets infectes par le virus de l’hepatite C. Les marqueurs tumoraux proteiques actuellement utilises, tels que l’alpha-fœtoproteine, sont insuffisants pour le diagnostic et le suivi satisfaisant des patients. Un grand nombre de genes porteurs d’alterations ont ete decrits dans le CHC, cependant les mecanismes de l’hepatocarcinogenese ne sont pas completement elucides. Ces genes regulent principalement quatre voies de signalisation intracellulaire, et chacune de ces voies parait concerner un nombre limite de tumeurs : la voie p53 impliquee dans la reponse aux alterations de l’ADN, la voie retinoblastoma dans la regulation du cycle cellulaire, la voie transforming growth factor-beta (TGF-beta) dans l’inhibition de la croissance cellulaire, et la voie Wnt dans les mecanismes d’adherence cellule-cellule et la transduction du signal. Une regulation epigenetique du fonctionnement de ces genes a egalement ete identifiee. L’evolution de la biologie moleculaire tend au developpement de methodes d’analyse plus globale du genome. Des methodes d’etude d’alterations genetiques telles que l’instabilite des microsatellites, l’instabilite chromosomique ou celle des profils d’expression genique ont ainsi ete evaluees dans le CHC. Enfin, des essais sont egalement realises dans le but de developper des tests bases sur l’analyse moleculaire du sang peripherique, moins invasifs et mieux adaptes a une utilisation clinique.