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Résumé: L'introduction du traitement par acide ursodésoxycholique a considérablement modifié l'histoire naturelle de la cholangite biliaire primitive. Les patients traités à un stade précoce et ayant une réponse biochimique ont une espérance de vie normale. La cholangite biliaire primitive a acquis au fil des années au sein de la communauté hépato-gastro-entérologique une « réputation » de maladie plutôt indolente alors que 40 % des patients sont non-répondeurs au traitement et que le taux de transplantation hépatique dans cette indication n'infléchit plus depuis 10 ans. Plusieurs scores permettent de mesurer le risque de mortalité chez les patients traités par acide ursodésoxycholique (score Globe, Score UK-PBC). Près de 12 % de la mortalité est prématurée et 80 % des décès surviennent avant d'atteindre l'espérance de vie à la naissance. La transplantation hépatique pour cholangite biliaire primitive apparaît stable dans le temps avec en moyenne entre 30 et 40 patients transplantés par an en France et 200 en Europe. Les indications de greffe sont hétérogènes : ictère en plateau, prurit réfractaire, complications de la cirrhose et carcinome hépatocellulaire. The introduction of ursodeoxycholic acid therapy have improved the natural history of primary biliary cholangitis. Patients treated at an early stage and having a biochemical response have a normal life expectancy. Primary biliary cholangitis has acquired over the years within the hepato-gastroenterological community a "reputation" as a rather indolent disease, whereas 40% of patients are non-responsive to treatment and the rate of liver transplantation in this indication does not change for 10 years. Several scores are used to measure the risk of mortality in patients treated with ursodeoxycholic acid (Globe score, UK-PBC score). Nearly 12% of mortality is premature and 80% of deaths occur before reaching life expectancy at birth. Liver transplantation for primary biliary cholangitis appears to be stable over time with an average of between 30 and 40 patients transplanted per year in France and 200 in Europe. The indications for transplantation are heterogeneous: jaundice, refractory pruritus, complications of cirrhosis and hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Abstract: Consequences of climate warming on tree phenology are readily observable, but little is known about the differences in phenological sensitivity to temperature between species and between populations within a species. The aim of the present study is to compare phenological sensitivities to temperature of seven woody species between each other and within-species between two geographical areas using both altitudinal and temporal gradients (Abies alba, Acer pseudoplatanus, Carpinus betulus, Fagus sylvatica, Fraxinus excelsior, Ilex aquifolium and Quercus petraea). The timing of leaf unfolding was monitored (i) over 2 years along two altitudinal gradients in the Pyrénées mountains (six species), and (ii) over 22 years in Fontainebleau forest (four species). Three species were present in both areas which allowed us to compare their phenological sensitivity to temperature over altitudinal and temporal gradients. Along altitudinal gradients, we observed for all species an advance in leaf unfolding with decreasing elevation, ranging from 11 to 34 days 1000m−1 for beech and oak, respectively. Across the temporal gradient, we found significant advances in leaf unfolding for oak (−0.42daysyear−1) and ash (−0.78daysyear−1) since 1976, whereas no significant advance was observed for beech and hornbeam. For both gradients and for all species, significant correlations were found between leaf unfolding dates and temperature, except for beech in the temporal study. Moreover, we highlighted that phenological sensitivity to temperature was very similar between the two geographically separated populations (Pyrénées and Fontainebleau forests). Thus, oak had the strongest sensitivity (−7.48 and −7.26days°C−1 in altitudinal and temporal gradient, respectively) and beech had the lowest (−2.09 and −2.03days°C−1). Our results suggest that population sensitivity to global warming might be stable for a given species, in spite of its possible local adaptation. [Copyright &y& Elsevier]

Background & Aims: We recently showed that alcoholic hepatitis (AH) is characterized by dedifferentiation of hepatocytes and loss of mature functions. Glucose metabolism is tightly regulated in healthy hepatocytes. We hypothesize that AH may lead to metabolic reprogramming of the liver, including dysregulation of glucose metabolism., Methods: We performed integrated metabolomic and transcriptomic analyses of liver tissue from patients with AH or alcoholic cirrhosis or normal liver tissue from hepatic resection. Focused analyses of chromatin immunoprecipitation coupled to DNA sequencing was performed. Functional in vitro studies were performed in primary rat and human hepatocytes and HepG2 cells., Results: Patients with AH exhibited specific changes in the levels of intermediates of glycolysis/gluconeogenesis, the tricarboxylic acid cycle, and monosaccharide and disaccharide metabolism. Integrated analysis of the transcriptome and metabolome showed the used of alternate energetic pathways, metabolite sinks and bottlenecks, and dysregulated glucose storage in patients with AH. Among genes involved in glucose metabolism, hexokinase domain containing 1 (HKDC1) was identified as the most up-regulated kinase in patients with AH. Histone active promoter and enhancer markers were increased in the HKDC1 genomic region. High HKDC1 levels were associated with the development of acute kidney injury and decreased survival. Increased HKDC1 activity contributed to the accumulation of glucose-6-P and glycogen in primary rat hepatocytes., Conclusions: Altered metabolite levels and messenger RNA expression of metabolic enzymes suggest the existence of extensive reprogramming of glucose metabolism in AH. Increased HKDC1 expression may contribute to dysregulated glucose metabolism and represents a novel biomarker and therapeutic target for AH., (Copyright © 2021. Published by Elsevier Inc.)

Laboratory tests can play an important role in assessment of alcoholic patients, including for evaluation of liver damage and as markers of alcohol intake. Evidence on test performance should lead to better selection of appropriate tests and improved interpretation of results. We compared laboratory test results from 1578 patients between cases (with alcoholic cirrhosis; 753 men, 243 women) and controls (with equivalent lifetime alcohol intake but no liver disease; 439 men, 143 women). Comparisons were also made between 631 cases who had reportedly been abstinent from alcohol for over 60 days and 364 who had not. ROC curve analysis was used to estimate and compare tests' ability to distinguish patients with and without cirrhosis, and abstinent and drinking cases. The best tests for presence of cirrhosis were INR and bilirubin, with areas under the ROC curve (AUCs) of 0.91 ± 0.01 and 0.88 ± 0.01, respectively. Confining analysis to patients with no current or previous ascites gave AUCs of 0.88 ± 0.01 for INR and 0.85 ± 0.01 for bilirubin. GGT and AST showed discrimination between abstinence and recent drinking in patients with cirrhosis, including those without ascites, when appropriate (and for GGT, sex-specific) limits were used. For AST, a cut-off limit of 85 units/L gave 90% specificity and 37% sensitivity. For GGT, cut-off limits of 288 units/L in men and 138 units/L in women gave 90% specificity for both and 40% sensitivity in men, 63% sensitivity in women. INR and bilirubin show the best separation between patients with alcoholic cirrhosis (with or without ascites) and control patients with similar lifetime alcohol exposure. Although AST and GGT are substantially increased by liver disease, they can give useful information on recent alcohol intake in patients with alcoholic cirrhosis when appropriate cut-off limits are used., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background & Aims: There is no histologic classification system to determine prognoses of patients with alcoholic hepatitis (AH). We identified histologic features associated with disease severity and created a histologic scoring system to predict short-term (90-day) mortality., Methods: We analyzed data from 121 patients admitted to the Liver Unit (Hospital Clinic, Barcelona, Spain) from January 2000 to January 2008 with features of AH and developed a histologic scoring system to determine the risk of death using logistic regression. The system was tested and updated in a test set of 96 patients from 5 academic centers in the United States and Europe, and a semiquantitative scoring system called the Alcoholic Hepatitis Histologic Score (AHHS) was developed. The system was validated in an independent set of 109 patients. Interobserver agreement was evaluated by weighted κ statistical analysis., Results: The degree of fibrosis, degree of neutrophil infiltration, type of bilirubinostasis, and presence of megamitochondria were independently associated with 90-day mortality. We used these 4 parameters to develop the AHHS to identify patients with a low (0-3 points), moderate (4-5 points), or high (6-9 points) risk of death within 90 days (3%, 19%, and 51%, respectively; P < .0001). The AHHS estimated 90-day mortality in the training and test sets with an area under the receiver operating characteristic value of 0.77 (95% confidence interval, 0.71-0.83). Interrater agreement values were 0.65 for fibrosis, 0.86 for bilirubinostasis, 0.60 for neutrophil infiltration, and 0.46 for megamitochondria. Interestingly, the type of bilirubinostasis predicted the development of bacterial infections., Conclusions: We identified histologic features associated with the severity of AH and developed a patient classification system that might be used in clinical decision making., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)