26
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Clinical epidemiology and disease burden of nonalcoholic fatty liver disease

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma (HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type II diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear to experience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis.

          Related collections

          Most cited references60

          • Record: found
          • Abstract: found
          • Article: not found

          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.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease

            Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease. To elucidate the molecular basis of NAFLD we performed an exome-wide association study of liver fat content. Three variants were associated with increased liver fat at the exome-wide significance level: two in PNPLA3, an established locus for NAFLD, and one (Glu167Lys) in TM6SF2, a gene of unknown function. The Glu167LysTM6SF2 variant was also associated with higher circulating levels of alanine transaminase, a marker of liver injury, and lower levels of LDL-cholesterol, triglycerides and alkaline phosphatase in 3 independent populations (n>80,000). Recombinant Glu167LysTM6SF2 produced 50% less protein than wild-type TM6SF2 when expressed in cultured hepatocytes. Adeno-associated virus-mediated shRNA knockdown of Tm6sf2 in mice increased liver triglyceride content 3-fold and decreased VLDL secretion by 50%. Taken together, these data indicate that TM6SF2 activity is required for normal VLDL secretion, and that impaired TM6SF2 function causally contributes to NAFLD.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease.

              Our objective was to estimate the strength of the effect of the I148M (rs738409 C/G) patatin-like phospholipase domain containing 3 (PNPLA3) variant on nonalcoholic fatty liver (NAFLD) and disease severity across different populations. We performed a systematic review by a meta-analysis; literature searches identified 16 studies. Our results showed that rs738409 exerted a strong influence not only on liver fat accumulation (GG homozygous showed 73% higher lipid fat content when compared with CC ones, data from 2,937 subjects; P < 1 × 10(-9) ), but also on the susceptibility of a more aggressive disease (GG homozygous had 3.24-fold greater risk of higher necroinflammatory scores and 3.2-fold greater risk of developing fibrosis when compared with CC homozygous; P < 1 × 10(-9) ; data from 1,739 and 2,251 individuals, respectively). Nonalcoholic steatohepatitis (NASH) was more frequently observed in GG than CC homozygous (odds ratio [OR] 3.488, 95% confidence interval [CI] 1.859-6.545, random model; P < 2 × 10(-4) ; data from 2,124 patients). Evaluation of the risk associated with heterozygosity for the variant suggests that the additive genetic model best explains the effect of rs738409 on the susceptibility to develop NAFLD. Nevertheless, carrying two G alleles does not seem to increase the risk of severe histological features. Meta-regression showed a negative correlation between male sex and the effect of rs738409 on liver fat content (slope: -2.45 ± 1.04; P < 0.02). The rs738409 GG genotype versus the CC genotype was associated with a 28% increase in serum alanine aminotransferase levels. By summarizing the amount of evidence, this study provided unequivocal evidence of rs738409 as a strong modifier of the natural history of NAFLD in different populations around the world. Copyright © 2011 American Association for the Study of Liver Diseases.
                Bookmark

                Author and article information

                Contributors
                Journal
                World J Gastroenterol
                World J. Gastroenterol
                WJG
                World Journal of Gastroenterology
                Baishideng Publishing Group Inc
                1007-9327
                2219-2840
                21 December 2017
                21 December 2017
                : 23
                : 47
                : 8263-8276
                Affiliations
                Department of Medicine, College of Medicine, Drexel University, Philadelphia, PA 19129, United States
                Division of Gastroenterology and Hepatology, Health Science Center, University of Tennessee, Memphis, TN 38163, United States
                Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA 95128, United States
                Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA 94304, United States
                Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA 94304, United States
                Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA 94304, United States. aijazahmed@ 123456stanford.edu
                Author notes

                Author contributions: Perumpail BJ, Khan MA, Kim D, Cholankeril G and Ahmed A drafted the manuscript; Cholankeril G and Ahmed A critically revised intellectual input; all authors approved the final manuscript.

                Correspondence to: Aijaz Ahmed, MD, Associate Professor, Attending Doctor, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 750 Welch Road # 210, Palo Alto, CA 94304, United States. aijazahmed@ 123456stanford.edu

                Telephone: +1-650-4986091 Fax: +1-650-4985692

                Article
                jWJG.v23.i47.pg8263
                10.3748/wjg.v23.i47.8263
                5743497
                29307986
                9102f848-9bd1-4985-8176-7d096f31cadc
                ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 22 October 2017
                : 8 November 2017
                : 4 December 2017
                Categories
                Review

                nonalcoholic fatty liver disease,hepatic steatosis,fatty liver,prevalence,incidence,fibrosis,risk factor,epidemiology,outcomes,nonalcoholic steatohepatitis

                Comments

                Comment on this article