Kastrupraun4783

Measures focused on taxation and price regulation have been shown to be the most effective at reducing alcohol-related mortality. IDF-11774 However, there are few studies focused on the effect of public policies on ALD. This review article summarises the factors influencing ALD burden and the role of different public health policies. © 2019 The Authors.CRISPR/Cas9 gene editing has revolutionised biomedical research. The ease of design has allowed many groups to apply this technology for disease modelling in animals. While the mouse remains the most commonly used organism for embryonic editing, CRISPR is now increasingly performed with high efficiency in other species. The liver is also amenable to somatic genome editing, and some delivery methods already allow for efficient editing in the whole liver. In this review, we describe CRISPR-edited animals developed for modelling a broad range of human liver disorders, such as acquired and inherited hepatic metabolic diseases and liver cancers. CRISPR has greatly expanded the repertoire of animal models available for the study of human liver disease, advancing our understanding of their pathophysiology and providing new opportunities to develop novel therapeutic approaches. © 2019 The Authors.Liver transplantation is widely indicated as a curative treatment for selected patients with hepatocellular carcinoma. However, with recent therapeutic advances, as well as efforts to increase the donor pool, liver transplantation has been carefully expanded to patients with other primary or secondary malignancies in the liver. Cholangiocarcinoma, colorectal and neuroendocrine liver metastases, and hepatic epithelioid haemangioendothelioma are amongst the most relevant new indications. In this review we discuss the fundamental concepts of this ambitious undertaking, as well as the newest indications for liver transplantation, with a special focus on future perspectives within the recently established concept of transplant oncology. © 2019 The Authors.Background & Aims Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammatory and fibrotic injury to the biliary tree. We sought to further delineate the contribution of macrophage lineages in PSC pathobiology. Methods Human liver tissues and/or blood samples from patients with PSC, primary biliary cholangitis, other non-cholestatic/non-autoimmune diseases, including alcohol-related liver disease and non-alcoholic steatohepatitis, as well as normal liver, were sourced from our liver transplantation program. Liver fibrosis was studied using Van Gieson staining, while the frequencies of infiltrating monocyte and macrophage lineages, both in the circulation and the liver, were investigated by flow cytometry, including the expression of TGR-5, a G protein-coupled receptor (GPBAR1/TGR-5). Results Significantly higher frequencies of CD68+CD206+ macrophages were detected in the livers of patients with PSC (median 19.17%; IQR 7.25-32.8%; n = 15) compared to thpression in PSC. Lay summary Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease associated with progressive inflammation of the bile duct, leading to fibrosis and end-stage liver disease. In this study we explore the role of a type of immune cell, the macrophage, in contributing to PSC as a disease, hoping that our findings direct scientists towards new treatment targets. Our findings based on human liver and blood analyses demonstrate a greater frequency of a particular subset of immune cell, the CD68+CD206+ macrophage, with significantly higher TGR-5 expression on this subset in PSC. © 2019 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).There is an urgent medical need to develop non-invasive tests for non-alcoholic steatohepatitis (NASH). This study evaluates the diagnostic performance of an innovative model based on mid-infrared (MIR) spectroscopy for the diagnosis of NASH. Methods Severely obese patients who underwent a bariatric procedure at the University Hospital of Nice, France (n = 395) were prospectively recruited. The clinico-biological characteristics were measured prior to surgery. Liver biopsies were collected during the surgical procedure and assessed by a pathologist. A training group (316 patients, NASH 16.8%) and a validation group (79 patients, NASH 16.5%) were randomly defined. MIR spectra were acquired by fiber evanescent wave spectroscopy, using chalcogenide glass fiber optic sensors and a spectrometer. This absorption spectroscopic technique delivers a spectrum that identifies the molecular composition of a sample, defining a patient's metabolic fingerprint. Results The areas under the receiver operating curve (AUROC) fo(MIR) spectroscopy. Using serum samples from severely obese patients who underwent a bariatric procedure, which enabled a concomitant liver biopsy to be performed, the MIR spectroscopy model performed well in screening patients for NASH compared to a traditional, histological diagnosis. © 2019 The Authors.Natural killer (NK) cells are key participants in the innate immune response. Killer cell immunoglobulin-like receptors (KIRs) are involved in the activation and inhibition of NK cells through the recognition of human leukocyte antigen (HLA) class I molecules. We investigated the impact of KIR/HLA combinations on susceptibility and long-term clinical outcome in Japanese patients with type 1 autoimmune hepatitis (AIH). Methods A total of 154 cases of AIH were recruited at Shinshu University Hospital between 1974 and 2018. KIR genes and HLA class I and II alleles were genotyped in all patients along with 201 healthy individuals. Associations between KIR/HLA pairs and clinical outcomes (liver decompensation and liver-related death) were evaluated using the Cox proportional hazards model with stepwise method. Results After a median follow-up period of 11.1 years, 12% of patients experienced liver decompensation and 8% died from liver disease. KIR3DL1/HLA-B Bw4-80Ile (p = 0.0062) and the HLA-DRB1*0405-DQB1*0401 haptibility or disease progression. KIR3DL1/HLA-B Bw4 was a novel KIR/HLA pair related to a favorable clinical outcome, while cirrhosis at the initial diagnosis was a risk factor for poor prognosis. Thus, frequent and careful surveillance is advised for KIR3DL1/HLA-B Bw4-negative patients with AIH and cirrhosis. © 2019 The Authors.