DHU Unity

Paris, France

DHU Unity

Paris, France
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PubMed | Clinique Ambroise Pare, Nancy University Hospital Center, DHU UNITY, Nice University Hospital Center and 2 more.
Type: Journal Article | Journal: Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver | Year: 2016

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of multifactorial etiology that primarily affects the colonic mucosa. The disease progresses over time, and clinical management guidelines should reflect its dynamic nature. There is limited evidence supporting UC management in specific clinical situations, thus precluding an evidence-based approach.To use a formal consensus method - the nominal group technique (NGT) - to develop a clinical practice expert opinion to outline simple algorithms and practices, optimize UC management, and assist clinicians in making treatment decisions.The consensus was developed by an expert panel of 37 gastroenterologists from various professional organizations with experience in UC management using the qualitative and iterative NGT, incorporating deliberations based on the European Crohns and Colitis Organisation recommendations, recent reviews of scientific literature, and pertinent discussion topics developed by a steering committee. Examples of clinical cases for which there are limited evidence-based data from clinical trials were used. Two working groups proposed and voted on treatment algorithms that were then discussed and voted for by the nominal group as a whole, in order to reach a consensus.A clinical practice guideline covering management of the following clinical situations was developed: (i) moderate and severe UC; (ii) acute severe UC; (iii) pouchitis; (iv) refractory proctitis, in the form of treatment algorithms.Given the limited available evidence-based data, a formal consensus methodology was used to develop simple treatment guidelines for UC management in different clinical situations that is now accessible via an online application.


PubMed | DHU Unity and Service dHepatologie
Type: Journal Article | Journal: Alimentary pharmacology & therapeutics | Year: 2016

Beta-blockers may have to be interrupted in patients with cirrhosis. The concept of a rebound after interruption of beta-blockers is based on an animal study and on isolated case reports of variceal bleeding.To determine if a rebound occurs in patients with cirrhosis following abrupt interruption of beta-blockers.We prospectively included all consecutive patients with cirrhosis undergoing right heart and hepatic vein catheterisation. Four groups were defined: no beta-blockers including patients not receiving beta-blockers; 1 day, 2-3 days and 4 days classified according to the time patients had interrupted beta-blockers before catheterisation. Results were expressed as median (interquartile range).A total of 150 patients were included. Among the 25 patients in the groups 2-3 days and 4 days, median duration of beta-blockers interruption was 4 (3-6) days. No gastrointestinal bleeding occurred during that period, nor during the following month. Hepatic venous pressure gradient was not different among patients in usually treated with beta-blockers. After adjustment, beta-blockers interruption was not associated with hepatic venous pressure gradient. Cardiac index was higher in the 4 days group [4.6 L/min/m(2) (3.5-5.1)] than in the 1 day group [3.4 (2.6-4.0); P = 0.001] or in the 2-3 days group [3.1 (2.7-3.7); P = 0.007], but not different from the no beta-blockers group.Abrupt interruption of beta-blockers is associated neither with an apparent increase in the risk of variceal bleeding nor with a haemodynamic rebound. Thus, interruption of beta-blockers in patients with cirrhosis may not require particular dosing or surveillance.


Kantari-Mimoun C.,French Institute of Health and Medical Research | Castells M.,French Institute of Health and Medical Research | Klose R.,French Institute of Health and Medical Research | Meinecke A.-K.,University of Duisburg - Essen | And 9 more authors.
Hepatology | Year: 2015

Angiogenesis is a key feature of liver fibrosis. Although sinusoidal remodeling is believed to contribute to fibrogenesis, the impact of sinusoidal angiogenesis on the resolution of liver fibrosis remains undefined. Myeloid cells, particularly macrophages, constantly infiltrate the fibrotic liver and can profoundly contribute to remodeling of liver sinusoids. We observe that the development of fibrosis is associated with decreased hepatic vascular endothelial growth factor (VEGF) expression as well as sinusoidal rarefication of the fibrotic scar. In contrast, the resolution of fibrosis is characterized by a rise in hepatic VEGF levels and revascularization of the fibrotic tissue. Genetic ablation of VEGF in myeloid cells or pharmacological inhibition of VEGF receptor 2 signaling prevents this angiogenic response and the resolution of liver fibrosis. We observe increased expression of matrix metalloproteases as well as decreased expression of tissue inhibitor of metalloproteases confined to sinusoidal endothelial cells in response to myeloid cell VEGF. Remarkably, reintroduction of myeloid cell-derived VEGF upon recovery restores collagenolytic acitivity and the resolution of fibrosis. Conclusion: We identify myeloid cell-derived VEGF as a critical regulator of extracellular matrix degradation by liver endothelial cells, thereby unmasking an unanticipated link between angiogenesis and the resolution of fibrosis. © 2014 by the American Association for the Study of Liver Diseases.


PubMed | DHU Unity, French Institute of Health and Medical Research, University of North Carolina at Chapel Hill and University of Barcelona
Type: | Journal: Hepatology (Baltimore, Md.) | Year: 2017

The diagnosis of alcoholic hepatitis (AH) often requires a transjugular liver biopsy (TJLB), a procedure not always readily accessible. We analyzed plasma biomarkers to estimate the presence of histological features of AH among patients with clinical suspicion of AH. Using ELISA, we tested M65 and M30 (circulating fragments of cytokeratin-18) and their respective fraction carried by microvesicles (MVs), CCL20 and TREM1. Leukocyte, platelet and endothelial-derived MVs were quantified by flow cytometry. Test and validation cohorts prospectively included patients with clinical features of AH undergoing TJLB. In the test cohort, 46/83 (55%) patients showed histological features of AH. ABIC score was B or C in 83%. Patients with histologically proven AH had higher levels of total and MV-bound M65, total and MV-bound M30 and CCL20 than those without (p<0.001 for all tests). Levels of TREM-1 and of subpopulations of MVs were not different between groups. M65 and M30 both had AUROCs of 0.84 to estimate the presence of AH. For M65, a cutoff of 2000 IU/L had a positive predictive value of 91%, while a cutoff of 641 IU/L had a negative predictive value of 88%. In the validation cohort, AH was histologically confirmed in 48/68 (71%) patients. ABIC score was B or C in 69%. For M65, the above cutoffs had a diagnostic accuracy of 81%. Even better results were obtained in patients with suspicion of severe AH (ABIC B or C) in both cohorts.Plasma levels of cytokeratin-18 fragments are reliable non-invasive markers of AH. Using the proposed cutoffs for M65, two thirds of TJLB can be avoided, which can be useful in centers where this technique is not readily available. This article is protected by copyright. All rights reserved.


Marzano C.,University of Rome La Sapienza | Cazals-Hatem D.,DHU UNITY | Cazals-Hatem D.,DHU Unity | Cazals-Hatem D.,University Paris Diderot | And 5 more authors.
Hepatology | Year: 2015

Sinusoidal dilatation found in the absence of an impaired sinusoidal blood outflow has been so far of unclear significance. Sinusoidal dilatation may actually be a nonspecific feature of impaired portal venous blood inflow, whatever the cause, or a feature of severe systemic inflammatory reaction syndrome, whatever the cause. Sinusoidal dilatation is mainly located in the centrilobular area even in the absence of an outflow block. A predominantly periportal location is specifically found in oral contraceptive users, associated with an inflammatory condition. There is strong evidence for the association of sinusoidal dilatation and oxaliplatin-based chemotherapy but not for estroprogestative steroids or thiopurine derivatives. Exposure to anabolic androgen steroids appears to cause sinusoidal changes different from a mere sinusoidal dilatation. Conclusion: There is evidence of activation of the interleukin-6 and vascular endothelial growth factor pathways in sinusoidal dilatation, but the mechanisms linking the activation of these pathways with the microvascular changes must be identified. © 2015 by the American Association for the Study of Liver Diseases.


Valla D.-C.,DHU UNITY | Valla D.-C.,University Paris Diderot | Rautou P.-E.,DHU UNITY | Rautou P.-E.,University of Paris Descartes
Liver International | Year: 2015

In patients with cirrhosis, routine laboratory tests for primary hemostasis and coagulation usually show anomalies that are associated with excess bleeding in other settings, in particular low platelet counts and prolonged prothrombin time. However, under conditions similar to those in vivo, primary hemostasis and thrombin production do not appear to be decreased in patients with cirrhosis, particularly when the platelet count is above 75 000/μl. Furthermore, there is laboratory and epidemiological evidence of a mild procoagulant and prothrombotic state in patients with cirrhosis. Bleeding is mainly because of portal hypertension rather than defective hemostasis. There is some evidence that anticoagulation therapy is not associated with an excess of severe bleeding and that it could improve the outcome in patients without portal vein thrombosis. At present, there is no clear evidence that portal vein thrombosis is responsible for the progression of liver disease and that anticoagulation therapy would improve the outcome of patients with portal vein thrombosis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Vion A.-C.,Cancer Research UK Research Institute | Rautou P.-E.,University of Paris Descartes | Rautou P.-E.,DHU UNITY | Durand F.,DHU UNITY | And 2 more authors.
Seminars in Thrombosis and Hemostasis | Year: 2015

Endothelial cells are unique multifunctional cells with basal and inducible metabolic and synthetic functions. Various stimuli can induce physiological or pathological changes in endothelial cell biology. Hematopoietic stem cell transplantation (HSCT) requires high-dose irradiation and/or chemotherapy and is associated with increased risk of bacterial infections and immune reactions. These factors can affect endothelial cells. This review provides an overview of the effects of HSCT on endothelial cells, based on findings observed in cultured cells as well as in patients. We first describe to what extent irradiation and chemotherapy constitute direct and indirect triggers for endothelial cell activation and injury. Then, we highlight the role of the endothelium in several complications of HSCT, including capillary leak syndrome, engraftment syndrome, transplant-associated microangiopathy, graft-versus-host disease, and diffuse alveolar hemorrhages. We also analyze in detail available data on sinusoidal obstruction syndrome, previously known as veno-occlusive disease of the liver, where liver sinusoidal endothelial cells are first injured and eventually lead to sinusoid occlusion and liver cell damage. Finally, we open the question of the possible contribution of endothelial damage to cardiovascular events occurring long after HSCT. © 2015 by Thieme Medical Publishers, Inc.


PubMed | Cancer Research UK Research Institute, DHU UNITY and University of Paris Descartes
Type: Journal Article | Journal: Seminars in thrombosis and hemostasis | Year: 2015

Endothelial cells are unique multifunctional cells with basal and inducible metabolic and synthetic functions. Various stimuli can induce physiological or pathological changes in endothelial cell biology. Hematopoietic stem cell transplantation (HSCT) requires high-dose irradiation and/or chemotherapy and is associated with increased risk of bacterial infections and immune reactions. These factors can affect endothelial cells. This review provides an overview of the effects of HSCT on endothelial cells, based on findings observed in cultured cells as well as in patients. We first describe to what extent irradiation and chemotherapy constitute direct and indirect triggers for endothelial cell activation and injury. Then, we highlight the role of the endothelium in several complications of HSCT, including capillary leak syndrome, engraftment syndrome, transplant-associated microangiopathy, graft-versus-host disease, and diffuse alveolar hemorrhages. We also analyze in detail available data on sinusoidal obstruction syndrome, previously known as veno-occlusive disease of the liver, where liver sinusoidal endothelial cells are first injured and eventually lead to sinusoid occlusion and liver cell damage. Finally, we open the question of the possible contribution of endothelial damage to cardiovascular events occurring long after HSCT.


PubMed | University Paul Sabatier, DHU UNITY and Hospital Clinic Institute Of Investigacions Biomediques August Pi I Sunyer Idibaps
Type: Journal Article | Journal: Hepatology (Baltimore, Md.) | Year: 2016

In patients with chronic noncirrhotic, nontumoral portal vein thrombosis (PVT), the usually recommended strategy for endoscopic screening and management of varices is the same as in cirrhosis. However, the efficacy of this policy in patients with PVT is unknown. We assessed the course of gastroesophageal varices in a large cohort of patients with chronic PVT. Patients prospectively registered in two referral centers for vascular liver disorders were eligible for the study. Endpoints were development and growth of varices and the incidence and outcome of portal hypertension-related bleeding. Included were 178 patients with chronic PVT. Median follow-up was 49 (1-598) months. Variceal bleeding was the initial manifestation in 27 (15%) patients. Initial endoscopy in the remaining 151 patients showed no varices in 52 (34%), small esophageal varices in 28 (19%), large esophageal varices (LEVs) in 60 (40%), and gastric varices without LEVs in 11 (7%). Ascites and splenomegaly were independent predictors for the presence of varices. In patients without varices, the probability of developing them was 2%, 22%, and 22% at 1, 3, and 5 years, respectively. In those with small esophageal varices, growth to LEVs was observed in 13%, 40%, and 54% at 1, 3, and 5 years, respectively. In patients with LEVs on primary prophylaxis, probability of bleeding was 9%, 20%, and 32% at 1, 3, and 5 years, respectively. Nine (5%) patients died after a median 51 (8-280) months, only one due to variceal bleeding.The course of varices in chronic noncirrhotic, nontumoral PVT appears to be similar to that in cirrhosis; using the same therapeutic approach as for cirrhosis is associated with a low risk of bleeding and death.


PubMed | University of Rome La Sapienza, DHU UNITY and DHU Unity
Type: Journal Article | Journal: Hepatology (Baltimore, Md.) | Year: 2015

Sinusoidal dilatation found in the absence of an impaired sinusoidal blood outflow has been so far of unclear significance. Sinusoidal dilatation may actually be a nonspecific feature of impaired portal venous blood inflow, whatever the cause, or a feature of severe systemic inflammatory reaction syndrome, whatever the cause. Sinusoidal dilatation is mainly located in the centrilobular area even in the absence of an outflow block. A predominantly periportal location is specifically found in oral contraceptive users, associated with an inflammatory condition. There is strong evidence for the association of sinusoidal dilatation and oxaliplatin-based chemotherapy but not for estroprogestative steroids or thiopurine derivatives. Exposure to anabolic androgen steroids appears to cause sinusoidal changes different from a mere sinusoidal dilatation.There is evidence of activation of the interleukin-6 and vascular endothelial growth factor pathways in sinusoidal dilatation, but the mechanisms linking the activation of these pathways with the microvascular changes must be identified.

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