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To evaluate the diagnostic performance of liver surface nodularity (LSN) for the assessment of advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). We retrospectively analysed patients with pathologically proven NAFLD who underwent liver MRI. Demographic, clinical, and laboratory data (including FIB-4 scores) were gathered. The SAF score was used to assess NAFLD. MRI-proton density fat fraction (PDFF) and LSN were determined on pre-contrast MR sequences. ROC curve analysis was performed to evaluate the diagnostic performance of MRI-LSN for the diagnosis of advanced (F3-F4) liver fibrosis. The final population included 142 patients. Sixty-seven (47%) patients had non-alcoholic steatohepatitis (NASH), and 52 (37%) had advanced fibrosis. The median MRI-PDFF increased with the grades of steatosis: 8.1%, 18.1%, and 31% in S1, S2, and S3 patients, respectively (p

OBJECTIVES: Alcoholic hepatitis (AH) is a severe condition characterized by a marked inflammatory response and high short-term mortality. Endothelial dysfunction (ED) is an early event in vascular and inflammatory disorders. The aim of this study is to evaluate ED in AH patients. METHODS: Prognostic value of ED biomarkers was evaluated in patients with severe AH (n = 67), compensated alcoholic cirrhosis (n = 15), heavy drinkers without liver disease (n = 15) and controls (n = 9), and in a validation cohort of 50 patients with AH. Gene expression of ED markers was analyzed in liver tissue. RESULTS: Plasma levels of ED markers such as vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin and von Willebrand factor (vWF) increased along alcohol-related liver disease (ALD) progression. Intergroup analysis showed a significant increase of these markers in AH patients. In addition, VCAM-1 showed a positive correlation with Maddrey, MELD and ABIC scores and inflammation parameters (i.e. C-reactive protein and LPS levels). Importantly, levels of VCAM-1 were higher in patients with increased mortality and were independently associated with short-term survival (90-day) when adjusted by ABIC score. These results were confirmed in an independent cohort of AH patients. In addition, severe AH patients showed altered hepatic expression of ED markers. CONCLUSIONS: In this study we show that advanced ALD and particularly severe AH is associated with an increase of ED biomarkers, which correlate with patient outcomes. These results suggest that ED may be a pathogenic event in AH and highlight endothelial factors as potential biomarkers in AH.

The aim of this study was to assess the prognostic value of liver surface nodularity (LSN) and sarcopenia from preoperative computed tomography (CT) in patients with resectable metabolic syndrome (MS)-related hepatocellular carcinoma (HCC).Patients with MS undergoing hepatectomy for HCC between 2006 and 2018 at a single center were retrospectively analyzed. LSN and sarcopenia were assessed on preoperative CT scans, and their association with severe (Clavien-Dindo grade 3-5) postoperative complications was analyzed on multivariate analysis. The influence of LSN and sarcopenia on overall survival (OS) and recurrence-free survival (RFS) was assessed.Overall, 110 patients (92 men [84%], mean 67.7 ± 7.7 years of age) were analyzed. Severe postoperative complications occurred in 34/110 (31%) patients. Patients with severe complications had a significantly higher LSN score (area under the receiver operating characteristic curve 0.68 ± 0.05, optimal cut-off 2.50) and were more frequently sarcopenic (47% vs. 13% without major complications, p 0.001). Multivariate analysis identified sarcopenia (odds ratio [OR] 6.51, 95% confidence interval [CI] 2.08-20.39; p 0.001), LSN 2.50 (OR 7.05, 95% CI 2.13-23.35; p 0.001), and preoperative portal vein embolization (PVE; OR 6.06, 95% CI 1.71-21.48; p = 0.005) as independent predictors of severe complications. LSN and sarcopenia had no influence on OS. Stratification according to a combination of LSN 2.50 and sarcopenia predicted the risk of severe postoperative complications from 7% (no sarcopenia and LSN ≤2.50) to 71% (sarcopenia and LSN 2.50; p 0.001), as well as RFS from 61 months (95% CI 40-82) to 17 months (95% CI 9-25; p = 0.033). Results remained significant in 52 patients without advanced fibrosis.The combination of LSN and sarcopenia derived from routine preoperative CT seems to help predict severe postoperative complications and stratification of RFS in patients with MS and resectable HCC.

To prospectively assess the role of the US attenuation imaging coefficient (AC) for the diagnosis and quantification of hepatic steatosis.One hundred and one patients underwent liver biopsy and US-AC measurement on the same day. Liver steatosis was graded according to biopsy as absent (S05%), mild (S1 5-33%), moderate (S2 33-66%), or severe (S366%); liver fibrosis was graded from F0 to F4. The correlation between AC and steatosis on pathology (%) was calculated using the Pearson correlation coefficient. The Student t or Mann-Whitney U test was used to compare continuous variables and ROC curve analysis was used to assess diagnostic performance of AC in diagnosing steatosis.Overall, 43 (42%), 35 (35%), 12 (12%), and 11 (11%) patients were classified as S0, S1, S2, and S3, respectively. The AC was positively correlated with steatosis as a continuous variable (%) on pathology (r = 0.58, p0.01). Patients with steatosis of any grade had a higher AC than those without steatosis (mean 0.77 ± 0.13 vs. 0.63 ± 0.09 dB/cm/MHz, respectively; p0.01, AUROC = 0.805). Patients with S2-S3 had a higher AC than patients with S0-1 (0.85 ± 0.11 vs. 0.67 ± 0.11 dB/cm/MHz, respectively; p0.01, AUROC = 0.892). AC0.69 dB/cm/MHz had a sensitivity and specificity of 76% and 86%, respectively, for diagnosing any grade of steatosis (S1-S3), and AC0.72 dB/cm/MHz had a sensitivity and specificity of 96% and 74%, respectively, for diagnosing S2-S3. The presence of advanced fibrosis (F3-F4) did not affect the calculated AC.The attenuation imaging coefficient is a promising quantitative technique for the non-invasive diagnosis and quantification of hepatic steatosis.• Measurement of the attenuation coefficient is achieved with a very high rate of technical success. • We found a significant positive correlation between the attenuation coefficient and the grade of steatosis on pathology. • The attenuation imaging coefficient is a promising quantitative technique for the noninvasive diagnosis and quantification of hepatic steatosis.

While the metabolic syndrome (MS) is being recognized as an important risk factor for intrahepatic cholangiocarcinoma (ICC), the outcomes of liver resection in this context remain poorly described. This study aims to report the short- and long-term results of hepatectomy for patients with MS as risk factor for the development of ICC (MS+). All patients undergoing hepatectomy for ICC between 2000 and 2016 at a single center were retrospectively analyzed. The perioperative outcomes of MS+ and ICC patients without MS (MS−) were compared. Among 115 resected ICC patients, 40 (34.8%) were MS+ and 75 (65.2%) were MS−. MS+ exhibited an increased Charlson comorbidity index (5 ± 2 vs. 2 ± 2, p

Idiopathic non-cirrhotic portal hypertension is described with a very heterogeneous terminology depending on the geographic origin of the patients and on the possible underlying causes of the disease. We aim here to review the current nomenclature and to the pathophysiological origins of this entity. In the past, a relevant number of definitions of this condition have been used in the literature, suggesting the presence of several distinct diseases. However, recent findings strongly suggest that there are some common denominators for this disease. Therefore, efforts should be made to develop a unified terminology encompassing the very essential features from clinical, histologic, imaging, laboratory and elastographic data. These findings suggest that the common localization of the disease is the portal and the sinusoidal compartment of the liver; therefore, a novel definition should be elaborated.

International audience; Membrane vesicles released in the extracellular space are composed of a lipid bilayer enclosing soluble cytosolic material and nuclear components. Extracellular vesicles include apoptotic bodies, exosomes, and microvesicles (also known previously as microparticles). Originating from different subcellular compartments, the role of extracellular vesicles as regulators of transfer of biological information, acting locally and remotely, is now acknowledged. Circulating vesicles released from platelets, erythrocytes, leukocytes, and endothelial cells contain potential valuable biological information for biomarker discovery in primary and secondary prevention of coronary artery disease. Extracellular vesicles also accumulate in human atherosclerotic plaques, where they affect major biological pathways, including inflammation, proliferation, thrombosis, calcification, and vasoactive responses. Extracellular vesicles also recapitulate the beneficial effect of stem cells to treat cardiac consequences of acute myocardial infarction, and now emerge as an attractive alternative to cell therapy, opening new avenues to vectorize biological information to target tissues. Although interest in microvesicles in the cardiovascular field emerged about 2 decades ago, that for extracellular vesicles, in particular exosomes, started to unfold a decade ago, opening new research and therapeutic avenues. This Review summarizes current knowledge on the role of extracellular vesicles in coronary artery disease, and their emerging potential as biomarkers and therapeutic agents.

To report the association of a mosaic enhancement pattern on contrast-enhanced CT or MR imaging and hepatic sinusoidal dilatation (SD) with acute inflammatory conditions affecting extrahepatic organs. From 2007 to 2012, patients with acute inflammatory diseases who underwent contrast-enhanced CT and/or MRI of the liver with a mosaic enhancement pattern were selected. Clinico-biological and other imaging features were collected at diagnosis and during follow-up. Sixteen patients were included (15 women, median age 27 years; range 18–68). Five women (33 %) were receiving oral contraceptives. Acute inflammatory diseases included pyelonephritis (n = 10), pancreatitis (n = 2), pneumonia (n = 1), septicemia (n = 1), active Crohn's disease (n = 1), and infectious colitis (n = 1). Median white blood cell count was 13,250 cells/μL (range 11,500-18,000 cells/μL) and CRP level 94 mg/L (range 60–121 mg/L). Mosaic enhancement pattern was present in the whole liver and was prominent in the subcapsular areas. Four patients underwent liver biopsy confirming SD. Eleven patients underwent follow-up imaging showing normalized aspect in 9/11 patients after a median of 2 months. Acute diseases of extrahepatic organs, associated with a marked systemic inflammatory syndrome should be added to the list of conditions causing a reversible hepatic sinusoidal dilatation as manifested by a mosaic enhancement pattern on contrast-enhanced CT or MR imaging. • Acute extrahepatic infectious/inflammatory diseases are a cause of transient MP. • In most patients, MP was seen during both arterial and portal venous phase. • In all patients, the mosaic enhancement pattern was diffuse, but more conspicuous in subcapsular areas. • MP was no longer seen after resolution of the acute disease. • No liver biopsy should be performed.

Microvesicles (MVs) are extracellular vesicles released by virtually all cells, under both physiological and pathological conditions. They contain lipids, proteins, RNAs and microRNAs and act as vectors of information that regulate the function of target cells. This Review provides an overview of the studies assessing circulating MV levels in patients with liver diseases, together with an insight into the mechanisms that could account for these changes. We also present a detailed analysis of the implication of MVs in key processes of liver diseases. MVs have a dual role in fibrosis as certain types of MVs promote fibrolysis by increasing expression of matrix metalloproteinases, whereas others promote fibrosis by stimulating processes such as angiogenesis. MVs probably enhance portal hypertension by contributing to intrahepatic vasoconstriction, splanchnic vasodilation and angiogenesis. As MVs can modulate vascular permeability, vascular tone and angiogenesis, they might contribute to several complications of cirrhosis including hepatic encephalopathy, hepatopulmonary syndrome and hepatorenal syndrome. Several results also suggest that MVs have a role in hepatocellular carcinoma. Although MVs represent promising biomarkers in patients with liver disease, methods of isolation and subsequent analysis must be standardized.

Early diagnosis of acute mesenteric ischemia (AMI) remains a clinical challenge, and no biomarker has been consistently validated. We aimed to assess the accuracy of three promising circulating biomarkers for diagnosing AMI—citrulline, intestinal fatty acid-binding protein (I-FABP), and d-lactate. A cross-sectional diagnostic study enrolled AMI patients admitted to the intestinal stroke center and controls with acute abdominal pain of another origin. We included 129 patients—50 AMI and 79 controls. Plasma citrulline concentrations were significantly lower in AMI patients compared to the controls [15.3 μmol/L (12.0–26.0) vs. 23.3 μmol/L (18.3–29.8), p = 0.001]. However, the area under the receiver operating curves (AUROC) for the diagnosis of AMI by Citrulline was low: 0.68 (95% confidence interval = 0.58–0.78). No statistical difference was found in plasma I-FABP and plasma d-lactate concentrations between the AMI and control groups, with an AUROC of 0.44, and 0.40, respectively. In this large cross-sectional study, citrulline, I-FABP, and d-lactate failed to differentiate patients with AMI from patients with acute abdominal pain of another origin. Further research should focus on the discovery of new biomarkers.