[Show abstract][Hide abstract] ABSTRACT: Subcutaneous adipose tissue (scAT) in human obesity undergoes severe alteration such as fibrosis which is related to metabolic alterations and to less efficiency in losing weight after bariatric surgery. There is currently no non-invasive tool to assess fibrosis in scAT. Vibration Controlled Transient Elastography (VCTE) using FibroScan® is widely used to assess liver fibrosis in clinical practice. A novel device named AdipoScan™ which is based on VCTE has been developed by Echosens (Paris) so as to assess scAT. The objective of this study is to show the first AdipoScan clinical results. AdipoScan™ was assessed in vivo on 73 morbidly obese patients candidate for bariatric surgery who were enrolled in the Pitié Salpêtrière hospital. scAT shear wave speed measured by AdipoScan™ is significantly associated with scAT fibrosis, gender, hypertension status, total body fat mass assessed by DXA, hypertension status, glycemic, lipid, hepatic parameters and adiponectin. Results suggest that scAT evaluation before bariatric surgery can be useful in clinical practice since it is related to scAT fibrosis -who plays in role in weight loss resistance after bariatric surgery- and to obesity induced co-morbidities such as diabetes, hypertension liver dysfunction.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
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.
No preview · Article · Nov 2015 · European Radiology
[Show abstract][Hide abstract] ABSTRACT: Background & aims:
Hereditary hemochromatosis is a heterogeneous group of genetic disorders characterized by parenchymal iron overload. It is caused by defective expression of liver hepcidin, the main regulator of iron homeostasis. Iron stimulates the gene encoding (HAMP) hepcidin via the BMP6 signaling to SMAD. Although several genetic factors have been found to cause late-onset hemochromatosis, many patients have unexplained signs of iron overload. We investigated BMP6 function in these individuals.
We sequenced the BMP6 gene in 70 consecutive patients with moderate increase in serum ferritin and liver iron who did not carry genetic variants associated with hemochromatosis. We searched for BMP6 mutations in relatives of 5 probands and in 200 healthy individuals (controls), as well as in two other independent cohorts of hyperferritinemia patients. We measured serum levels of hepcidin by liquid chromatography-tandem mass spectrometry and analyzed BMP6 in liver biopsies from patients by immunohistochemistry. The functions of mutant and normal BMP6 were assessed in transfected cells using immunofluorescence, real-time quantitative PCR, and immunoblot analyses.
We identified 3 heterozygous missense mutations in BMP6 (p.Pro95Ser, p.Leu96Pro, and p.Gln113Glu) in 6 unrelated patients with unexplained iron overload (9% of our cohort). These mutations were detected in less than 1% of controls. The p.Leu96Pro was also found in 2 patients from the additional cohorts. Family studies indicated dominant transmission. Serum levels of hepcidin were inappropriately low in patients. A low level of BMP6, compared with controls, was found in a biopsy from 1 patient. In cell lines, the mutated residues in the BMP6 propeptide resulted in defective secretion of BMP6; reduced signaling via SMAD1, SMAD5, and SMAD8; and loss of hepcidin production.
We identified 3 heterozygous missense mutations in BMP6 in patients with unexplained iron overload. These mutations lead to loss of signaling to SMAD proteins and reduced hepcidin production. These mutations might increase susceptibility to mild-to-moderate late onset iron overload.
[Show abstract][Hide abstract] ABSTRACT: Background and aims: Although potentially very useful in optimizing patient selection and follow-up, the individual response to transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) is generally unpredictable. The aim of this study was to identify tissue predictors of tumor resistance to TACE for use in clinical practice on pre-treatment biopsies.
Methods: We investigated the association of residual tumor in post-TACE-resected HCC with pathological and immunophenotypical features, mainly related to hypoxia and angiogenesis. Comparison of tumor phenotype between post-TACE HCC and both paired pre-TACE biopsies and control TACE-untreated HCC was performed. Cases showing >50% residual tumor (RT) were defined as TACE-resistant.
Results: A consecutive series of 108 HCC from 41 patients was studied. Overall, 45/108 (44%) HCC were classified as TACE-resistant. Among these, 32 (71%) and 40 (89%) showed diffuse CD34 vascular staining and negative VEGF staining, respectively (p<0.05). The association of these 2 parameters in a weighted score (TRIP) was able to predict TACE resistance with 81% accuracy, 89% sensitivity and 59% specificity. The effectiveness of TRIP was validated in an independent series of 28 HCC biopsies from patients subsequently treated with TACE and for whom radiologic follow-up was available.
Conclusion: This study demonstrates the potential value of pre-treatment tumor biopsy as predictors of TACE resistance in HCC. This article is protected by copyright. All rights reserved.
No preview · Article · Oct 2015 · Liver International
[Show abstract][Hide abstract] ABSTRACT: Background & aims:
A novel controlled attenuation parameter (CAP) using the signals acquired by the FibroScan® has been developed as a method for evaluating steatosis. The aim of this study is to assess the performance of the CAP for the detection and quantification of steatosis in patients with chronic hepatitis B (CHB).
Material and methods:
136 subjects with CHB underwent liver biopsy and FibroScan® within 60 days. CAP was evaluated retrospectively using raw FibroScan® data. Steatosis was graded as follows: S0 (steatosis < 10% of hepatocytes), S1 (10 to < 30%), S2 (30 to < 60%) or S3 (≥ 60%). Performance was evaluated by area under the receiver operating characteristic (AUROC) curve.
Proportions of each steatosis grade (S0-S3) were 78, 10, 9 and 3%, respectively. Using univariate analysis, liver stiffness measurement (LMS) significantly correlated with fibrosis (τ = 0.43; P < 10-10), sex, necro-inflammatory activity, steatosis, age, NASH, and perisinusoidal fibrosis, and with liver fibrosis (P < 10-8) and perisinusoidal fibrosis (P = 0.008) using multivariate analysis. CAP correlated with steatosis (τ = 0.38, P < 10-7), body mass index, NASH, fibrosis and perisinusoidal fibrosis using univariate analysis, but only steatosis (P < 10-10) and perisinusoidal fibrosis (P = 0.002) using multivariate analysis. AUROCs for LSM were: 0.77 (0.69-0.85), 0.87 (0.80-0.95), and 0.93 (0.83-1.00), respectively, for fibrosis stages F ≥ 2, F ≥ 3 and F = 4. AUROCs for CAP were: 0.82 (0.73-0.92), 0.82 (0.69-0.95), and 0.97 (0.84-1.00) for ≥ S1, ≥ S2 and S3 steatosis, respectively.
In conclusión CAP is a novel, accurate non-invasive tool and may be suitable for detecting and quantifying steatosis in CHB patients.
No preview · Article · Sep 2015 · Annals of hepatology: official journal of the Mexican Association of Hepatology
[Show abstract][Hide abstract] ABSTRACT: Previous studies suggested that microRNA-21 may be upregulated in the liver in non-alcoholic steatohepatitis (NASH), but its role in the development of this disease remains unknown. This study aimed to determine the role of microRNA-21 in NASH.
We inhibited or suppressed microRNA-21 in different mouse models of NASH: (a) low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice fed a high-fat diet and treated with antagomir-21 or antagomir control; (b) microRNA-21-deficient and wild-type mice fed a methionine-choline-deficient (MCD) diet; (c) peroxisome proliferation-activator receptor α (PPARα)-deficient mice fed an MCD diet and treated with antagomir-21 or antagomir control. We assessed features of NASH and determined liver microRNA-21 levels and cell localisation. MicroRNA-21 levels were also quantified in the liver of patients with NASH, bland steatosis or normal liver and localisation was determined.
Inhibiting or suppressing liver microRNA-21 expression reduced liver cell injury, inflammation and fibrogenesis without affecting liver lipid accumulation in Ldlr(-/-) fed a high-fat diet and in wild-type mice fed an MCD diet. Liver microRNA-21 was overexpressed, primarily in biliary and inflammatory cells, in mouse models as well as in patients with NASH, but not in patients with bland steatosis. PPARα, a known microRNA-21 target, implicated in NASH, was decreased in the liver of mice with NASH and restored following microRNA-21 inhibition or suppression. The effect of antagomir-21 was lost in PPARα-deficient mice.
MicroRNA-21 inhibition or suppression decreases liver injury, inflammation and fibrosis, by restoring PPARα expression. Antagomir-21 might be a future therapeutic strategy for NASH.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
[Show abstract][Hide abstract] ABSTRACT: Nodular regenerative hyperplasia (NRH) of the liver is associated with several diseases and drugs. Clinical symptoms of NRH may vary from absence of symptoms to full-blown (non-cirrhotic) portal hypertension. However, diagnosing NRH is challenging. The objective of this study was to determine inter- and intraobserver agreement on the histopathologic diagnosis of NRH.
Liver specimens (n=48) previously diagnosed as NRH, were reviewed for the presence of NRH by seven pathologists without prior knowledge of the original diagnosis or clinical background. The majority of the liver specimens were from thiopurine using inflammatory bowel disease patients. Histopathologic features contributing to NRH were also assessed. Criteria for NRH were modified by consensus and subsequently validated. Interobserver agreement was evaluated by using the standard kappa index.
After review, definite NRH, inconclusive NRH and no NRH were found in 35% (23-40%), 21% (13-27%) and 44% (38-56%), respectively (median, IQR). The median interobserver agreement for NRH was poor (κ = 0.20, IQR 0.14-0.28). The intraobserver variability on NRH ranged between 14% and 71%. After modification of the criteria and exclusion of biopsies with technical shortcomings, the interobserver agreement on the diagnosis NRH was fair (κ = 0.45).
The interobserver agreement on the histopathologic diagnosis of NRH was poor, even when assessed by well-experienced liver pathologists. Modification of the criteria of NRH based on consensus effort and exclusion of biopsies of poor quality led to a fairly increased interobserver agreement. The main conclusion of this study is that NRH is a clinicopathologic diagnosis that cannot reliably be based on histopathology alone.
[Show abstract][Hide abstract] ABSTRACT: The diagnostic assessment of liver fibrosis, a major determinant of disease severity, is an important step in the management of patients with chronic liver diseases. Liver biopsy is still considered the gold standard for the assessment of necroinflammation and fibrosis; however, recent technical advances have resulted in the development of numerous serum biomarkers and imaging tools as noninvasive alternatives to biopsy. These tests include biological (serum biomarker algorithms), physical (imaging assessment of tissue stiffness), and physiological (breath test) methods. Accumulating evidence shows that noninvasive tests provide prognostic information of clinical relevance, which has led to their incorporation into clinical guidelines and everyday practice. Here, the authors review and compare invasive and noninvasive tests for the diagnosis of liver fibrosis. They discuss emerging functional genomic, microparticle, protein-profiling, and bioimaging tools, focusing on novel sensitive tools that are able to assess the dynamic nature of fibrogenesis, a key requirement for the assessment of the efficacy of antifibrotic compounds in the future.
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No preview · Article · May 2015 · Seminars in Liver Disease
[Show abstract][Hide abstract] ABSTRACT: Although potentially very useful in optimizing patient selection and follow-up, the individual response to transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) is generally unpredictable. The aim of this study was to identify tissue predictors of tumor resistance to TACE for use in clinical practice on pre-treatment biopsies.
We investigated the association of residual tumor in post-TACE-resected HCC with pathological and immunophenotypical features, mainly related to hypoxia and angiogenesis. Comparison of tumor phenotype between post-TACE HCC and both paired pre-TACE biopsies and control TACE-untreated HCC was performed. Cases showing >50% residual tumor (RT) were defined as TACE-resistant.
A consecutive series of 108 HCC from 41 patients was studied. Overall, 45/108 (44%) HCC were classified as TACE-resistant. Among these, 32 (71%) and 40 (89%) showed diffuse CD34 vascular staining and negative VEGF staining, respectively (p<0.05). The association of these 2 parameters in a weighted score (TRIP) was able to predict TACE resistance with 81% accuracy, 89% sensitivity and 59% specificity. The effectiveness of TRIP was validated in an independent series of 28 HCC biopsies from patients subsequently treated with TACE and for whom radiologic follow-up was available.
This study demonstrates the potential value of pre-treatment tumor biopsy as predictors of TACE resistance in HCC. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
No preview · Article · Apr 2015 · Liver international: official journal of the International Association for the Study of the Liver