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      Current Status in Testing for Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH)

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          Abstract

          Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries with almost 25% affected adults worldwide. The growing public health burden is getting evident when considering that NAFLD-related liver transplantations are predicted to almost double within the next 20 years. Typically, hepatic alterations start with simple steatosis, which easily progresses to more advanced stages such as nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis. This course of disease finally leads to end-stage liver disease such as hepatocellular carcinoma, which is associated with increased morbidity and mortality. Although clinical trials show promising results, there is actually no pharmacological agent approved to treat NASH. Another important problem associated with NASH is that presently the liver biopsy is still the gold standard in diagnosis and for disease staging and grading. Because of its invasiveness, this technique is not well accepted by patients and the method is prone to sampling error. Therefore, an urgent need exists to find reliable, accurate and noninvasive biomarkers discriminating between different disease stages or to develop innovative imaging techniques to quantify steatosis.

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          Most cited references101

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          Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease

          Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem of unknown etiology that varies in prevalence among ethnic groups. To identify genetic variants contributing to differences in hepatic fat content, we performed a genome-wide association scan of nonsynonymous sequence variations (n=9,229) in a multiethnic population. An allele in PNPLA3 (rs738409; I148M) was strongly associated with increased hepatic fat levels (P=5.9×10−10) and with hepatic inflammation (P=3.7×10−4). The allele was most common in Hispanics, the group most susceptible to NAFLD; hepatic fat content was > 2-fold higher in PNPLA3-148M homozygotes than in noncarriers. Resequencing revealed another allele associated with lower hepatic fat content in African-Americans, the group at lowest risk of NAFLD. Thus, variation in PNPLA3 contributes to ethnic and inter-individual differences in hepatic fat content and susceptibility to NAFLD.
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            Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease.

            To optimize management of nonalcoholic fatty liver disease (NAFLD), a simple screening tool is necessary. In this study, we aimed to devise a simple index of NAFLD. A cross-sectional study with 10,724 health check-up subjects (5362 cases with NAFLD versus age- and sex-matched controls) was conducted. Study subjects were randomly assigned to a derivation cohort or a validation cohort. Multivariate analysis indicated that high serum alanine aminotransferase (ALT) to serum aspartate aminotransferase (AST) ratio, high body mass index (BMI), and diabetes mellitus were independent risk factors of NAFLD (all P 36.0, HSI ruled out NAFLD with a sensitivity of 93.1%, or detected NAFLD with a specificity of 92.4%, respectively. Of 2692 subjects with HSI 36.0 in the derivation cohort, 2305 (85.6%) were correctly classified. HSI was validated in the subsequent validation cohort. HSI is a simple, efficient screening tool for NAFLD that may be utilized for selecting individuals for liver ultrasonography and for determining the need for lifestyle modifications. (c) 2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
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              Noninvasive Assessment of Liver Disease in Patients With Nonalcoholic Fatty Liver Disease

              Nonalcoholic fatty liver disease (NAFLD) is estimated to afflict approximately 1 billion individuals worldwide. In a subset of NAFLD patients, who have the progressive form of NAFLD termed nonalcoholic steatohepatitis (NASH), it can progress to advanced fibrosis, cirrhosis, hepatocellular carcinoma, and liver-related morbidity and mortality. NASH is typically characterized by a specific pattern on liver histology, including steatosis, lobular inflammation, and ballooning with or without peri-sinusoidal fibrosis. Thus, key issues in NAFLD patients are the differentiation of NASH from simple steatosis and identification of advanced hepatic fibrosis. Until now, liver biopsy has been the gold standard for identifying these 2 critical end points, but has well-known limitations, including invasiveness; rare but potentially life-threatening complications; poor acceptability; sampling variability; and cost. Furthermore, due to the epidemic proportion of individuals with NAFLD worldwide, liver biopsy evaluation is impractical, and noninvasive assessment for the diagnosis of NASH and fibrosis is needed. Although much of the work remains to be done in establishing cost-effective strategies for screening for NASH, advanced fibrosis, and cirrhosis, in this review, we summarize the current state of the noninvasive assessment of liver disease in NAFLD, and we provide an expert synthesis of how these noninvasive tools could be utilized in clinical practice. Finally, we also list the key areas of research priorities in this area to move forward clinical practice.
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                Author and article information

                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                07 August 2019
                August 2019
                : 8
                : 8
                : 845
                Affiliations
                [1 ]Gastrointestinal Unit and Liver Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
                [2 ]Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital, 52074 Aachen, Germany
                Author notes
                Author information
                https://orcid.org/0000-0001-9945-1239
                https://orcid.org/0000-0003-3888-0931
                Article
                cells-08-00845
                10.3390/cells8080845
                6721710
                31394730
                52dfcf30-3768-4003-875b-c08fea504fc7
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 23 July 2019
                : 06 August 2019
                Categories
                Review

                nonalcoholic steatohepatitis,fibrosis,grading,staging,imaging,algorithms,scores,biomarkers

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