Combination of Gene Expression Signature and Model for End-Stage Liver Disease Score Predicts Survival of Patients With Severe Alcoholic Hepatitis.

BACKGROUND & AIMS: Patients with severe alcoholic hepatitis (AH) have a high risk of death within 90 days. Corticosteroids, which can cause severe adverse events, are the only treatment that increases short-term survival. It is a challenge to predict outcomes of patients with severe AH. Therefore, we developed a scoring system to predict patient survival, integrating baseline molecular and clinical variables. METHODS: We obtained fixed liver biopsy samples from 71 consecutive patients diagnosed with severe AH and treated with corticosteroids from July 2006 through December 2013 in Brussels, Belgium (derivation cohort). Gene expression patterns were analyzed by microarrays and clinical data were collected for 180 days. We identified gene expression signatures and clinical data that are associated with survival without liver transplantation at 90 and 180 days after initiation of corticosteroid therapy. Findings were validated using liver biopsies from 48 consecutive patients with severe AH treated with corticosteroids, collected from March 2010 through February 2015 at hospitals in Belgium and Switzerland (validation cohort 1) and in liver biopsies from 20 patients (9 received corticosteroid treatment), collected from January 2012 through May 2015 in the United States (validation cohort 2). RESULTS: We integrated data on expression patterns of 123 genes and the model for end-stage liver disease (MELD) scores to assign patients to groups with poor survival (29% survived 90 days and 26% survived 180 days) and good survival (76% survived 90 days and 65% survived 180 days) (P < .001) in the derivation cohort. We named this assignment system the gene signature-MELD (gs-MELD) score. In validation cohort 1, the gs-MELD score discriminated patients with poor survival (43% survived 90 days) from those with good survival (96% survived 90 days) (P < .001). The gs-MELD score also discriminated between patients with a poor survival at 180 days (34% survived) and a good survival at 180 days (84% survived) (P < .001). The time-dependent area under the receiver operator characteristic curve for the score was 0.86 (95% confidence interval 0.73-0.99) for survival at 90 days, and 0.83 (95% confidence interval 0.71-0.96) for survival at 180 days. This score outperformed other clinical models to predict survival of patients with severe AH in validation cohort 1. In validation cohort 2, the gs-MELD discriminated patients with a poor survival at 90 days (12% survived) from those with a good survival at 90 days (100%) (P < .001). CONCLUSIONS: We integrated data on baseline liver gene expression pattern and the MELD score to create the gs-MELD scoring system, which identifies patients with severe AH, treated or not with corticosteroids, most and least likely to survive for 90 and 180 days.

[Functional gastrointestinal disorders: update on the Rome IV criteria]. / Maladies fonctionnelles digestives: mise au point concernant la classification Rome IV.

Functional gastrointestinal disorders are highly prevalent worldwide and may have an important impact on the quality of life of affected patients. In addition, they are associated with a major socio-economic impact. In 2016 the Rome IV criteria were published that provided an update of the 2006 published Rome III criteria for functional gastrointestinal disorders. This article provides an overview of the current classification of functional gastrointestinal disorders and highlights the most important changes incorporated into the Rome IV criteria.

Les maladies fonctionnelles digestives représentent des entités fréquentes dans la pratique clinique du gastroentérologue. Elles sont associées à une baisse de la qualité de vie des patients concernés et ont un impact socio-économique important. Les critères du groupe de travail de Rome permettent de les classifier selon l'atteinte principale et le symptôme prédominant. Cet article résume les changements les plus importants dans les critères diagnostiques Rome IV qui ont été publiés en 2016.

[Benign focal liver lesions: a clinical, radiological and pathological review]. / Lésions hépatiques focales bénignes : revue clinique, radiologique et pathologique.

Benign focal liver lesions are a heterogeneous group of tumors of different cellular origin. They might develop from mesenchymal cells, hepatocytes or cholangiocytes. They are more often detected due to the increasing number of imaging investigations and the excellent performance of the new ultrasound machines. The imaging findings have to be interpreted while bearing the patient's clinical context in mind. The aim of this review is to discuss the three most frequent benign focal hepatic lesions : hemangioma, focal nodular hyperplasia and hepatocellular adenoma.

Les lésions hépatiques focales bénignes constituent un groupe d'entités hétérogènes d'origines cellulaires différentes, mésenchymateuses, hépatocytaires ou cholangiocytaires. La découverte fortuite d'une ou de plusieurs lésions hépatiques est de plus en plus courante en raison de l'utilisation plus fréquente d'examens d'imagerie et des performances excellentes des nouvelles machines d'échographie. Il est indispensable de toujours interpréter l'imagerie hépatique au regard des données cliniques et biologiques. Le but de cet article est de discuter les trois lésions hépatiques bénignes les plus répandues : l'hémangiome, l'hyperplasie nodulaire focale et l'adénome hépatocel-lulaire.

Autoimmune Gastritis in the Pediatric Age: An Underestimated Condition Report of Two Cases and Review.

Background: Diagnosis of pediatric autoimmune gastritis (AIG) in children is important due to poor outcome and risk of malignancy. This condition is often underestimated in the clinico-pathologic diagnostic work-up, leading to delayed time-to-diagnosis. To increase the awareness of this condition in the pediatric population, we present two cases encountered at our institution, discuss their clinical, biological, and histological presentations in relation with evidence from the literature, and propose an algorithm for diagnosis and follow-up of AIG in children. Case presentation: Two patients (12 and 17 years old) presented with iron deficiency anemia and negative family history for autoimmune disorders. In both cases, the final diagnosis of autoimmune gastritis was delayed until pathological examination of endoscopic gastric biopsies showed atrophy of oxyntic glands. Helicobacter pylori search was negative. Follow up biopsies revealed persistent disease. Literature review on this condition shows unclear etiology and poor long term outcome in some patients because of increased risk of malignancy. Conclusions: AIG should be considered in the differential diagnosis of iron deficiency anemia in the pediatric population.Standardized clinico-pathologic work-up is mandatory. Endoscopic follow-up should be performed due to the risk of malignancy.

Frequency and type of drug-related side effects necessitating treatment discontinuation in the Swiss Inflammatory Bowel Disease Cohort.

BACKGROUND AND AIM: Systematic analyses of inflammatory bowel disease (IBD) drug-related side effects necessitating treatment cessation in large cohorts of patients with IBD are scarce. We aimed to assess the frequency and type of drug-related side effects requiring drug cessation in patients included in the Swiss IBD Cohort. PATIENTS AND METHODS: A retrospective review was performed of data from the Swiss IBD Cohort physician questionnaires documenting a treatment cessation for the following drug categories: aminosalicylates, topical and systemic steroids, thiopurines, methotrexate, tumor necrosis factor-antagonists, and calcineurin inhibitors (tacrolimus, cyclosporine). RESULTS: A total of 3192 patients were analyzed, of whom 1792 (56.1%) had Crohn's disease, 1322 (41.4%) had ulcerative colitis, and 78 (2.5%) had IBD unclassified. Of 3138 patients treated with IBD drugs, 2129 (67.8%) presented with one or several drug-related side effects necessitating drug cessation. We found a significant positive correlation between the number of concomitantly administered IBD drugs and the occurrence of side effects requiring drug cessation (P<0.001). Logistic regression modeling identified Crohn's disease diagnosis [odds ratio (OR)=1.361, P=0.017], presence of extraintestinal manifestations (OR=2.262, P<0.001), IBD-related surgery (OR=1.419, P=0.006), and the increasing number of concomitantly used IBD drugs [OR=2.007 (P<0.001) for two concomitantly used IBD drugs; OR=3.225 (P<0.001) for at least three concomitantly used IBD drugs] to be associated significantly with the occurrence of IBD drug-related adverse events that necessitated treatment cessation. CONCLUSION: Physicians should keep in mind that the number of concomitantly administered IBD drugs is the main risk factor for drug-related adverse events necessitating treatment cessation.