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Cause, Pathogenesis, and Treatment of Nonalcoholic Steatohepatitis

Published on Nov 23, 2017in The New England Journal of Medicine 70.67
· DOI :10.1056/NEJMra1503519
Anna Mae Diehl98
Estimated H-index: 98
,
Christopher P. Day82
Estimated H-index: 82
Cite
Abstract
Nonalcoholic steatohepatitis is a major cause of cirrhosis and liver cancer. It is associated with visceral adiposity and the metabolic syndrome and is nearly as common as type 2 diabetes. Metabolic stress, inflammation, and fibrosis are the primary pathogenic mechanisms.
  • References (58)
  • Citations (95)
Cite
References58
Newest
Published on Jul 1, 2017in Gut 17.94
Timothy Hardy8
Estimated H-index: 8
(Newcastle University),
Müjdat Zeybel10
Estimated H-index: 10
(Koç University)
+ 10 AuthorsJeremy French4
Estimated H-index: 4
(Newcastle upon Tyne Hospitals NHS Foundation Trust)
Objective Liver biopsy is currently the most reliable way of evaluating liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Its inherent risks limit its widespread use. Differential liver DNA methylation of peroxisome proliferator-activated receptor gamma (PPARγ) gene promoter has recently been shown to stratify patients in terms of fibrosis severity but requires access to liver tissue. The aim of this study was to assess whether DNA methylation of circulating DNA could be...
Published on Dec 1, 2016in Cancer Cell 23.92
Nicole Michelle Kettner6
Estimated H-index: 6
(BCM: Baylor College of Medicine),
Horatio Voicu1
Estimated H-index: 1
(BCM: Baylor College of Medicine)
+ 7 AuthorsLoning Fu14
Estimated H-index: 14
(BCM: Baylor College of Medicine)
Summary Chronic jet lag induces spontaneous hepatocellular carcinoma (HCC) in wild-type mice following a mechanism very similar to that observed in obese humans. The process initiates with non-alcoholic fatty liver disease (NAFLD) that progresses to steatohepatitis and fibrosis before HCC detection. This pathophysiological pathway is driven by jet-lag-induced genome-wide gene deregulation and global liver metabolic dysfunction, with nuclear receptor-controlled cholesterol/bile acid and xenobioti...
Published on Nov 1, 2016in Hepatology 14.97
Zobair M. Younossi76
Estimated H-index: 76
,
Deirdre Blissett1
Estimated H-index: 1
+ 6 AuthorsRachel Beckerman1
Estimated H-index: 1
Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease. There is uncertainty around the economic burden of NAFLD. We constructed a steady-state prevalence model to quantify this burden in the United States and Europe. Five models were constructed to estimate the burden of NAFLD in the United States and four European countries. Models were built using a series of interlinked Markov chains, each representing age increments of the NAFLD and the general populations. Incid...
Published on Oct 1, 2016in Journal of Biological Rhythms 2.47
Tiffany Fleet2
Estimated H-index: 2
(BCM: Baylor College of Medicine),
Erin Stashi8
Estimated H-index: 8
(BCM: Baylor College of Medicine)
+ 8 AuthorsBert W. O'Malley115
Estimated H-index: 115
(BCM: Baylor College of Medicine)
Circadian rhythmicity is a fundamental process that synchronizes behavioral cues with metabolic homeostasis. Disruption of daily cycles due to jet lag or shift work results in severe physiological consequences including advanced aging, metabolic syndrome, and even cancer. Our understanding of the molecular clock, which is regulated by intricate positive feedforward and negative feedback loops, has expanded to include an important metabolic transcriptional coregulator, Steroid Receptor Coactivato...
Published on Aug 1, 2016in Metabolism-clinical and Experimental 6.51
Paola Dongiovanni38
Estimated H-index: 38
(Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico),
Luca Valenti48
Estimated H-index: 48
(Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico)
Abstract Epidemiological, familial, and twin studies indicate that non-alcoholic fatty liver disease, now the leading cause of liver damage in developed countries, has a strong heritability. The common I148M variant of PNPLA3 impairing hepatocellular lipid droplets remodeling is the major genetic determinant of hepatic fat content. The I148M variant has a strong impact on the full spectrum of liver damage related to fatty liver, encompassing non-alcoholic steatohepatitis, advanced fibrosis, and ...
Published on Jul 2, 2016in Expert Opinion on Emerging Drugs 3.23
Mazen Noureddin13
Estimated H-index: 13
(Cedars-Sinai Medical Center),
Alice Zhang1
Estimated H-index: 1
(Cedars-Sinai Medical Center),
Rohit Loomba53
Estimated H-index: 53
(UCSD: University of California, San Diego)
ABSTRACTIntroduction: Non-alcoholic fatty liver disease (NAFLD) has become the most common etiology for abnormal aminotransferase levels and chronic liver disease. Its growing prevalence is largely linked to the presence of metabolic syndrome, particularly diabetes and insulin resistance. It is estimated that 60–80% of the type 2 diabetic population has NAFLD. NAFLD encompasses a range of conditions ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). A subset of patients with ...
Published on Jul 1, 2016in Hepatology 14.97
Zobair M. Younossi76
Estimated H-index: 76
,
Aaron B. Koenig6
Estimated H-index: 6
+ 3 AuthorsMark Wymer1
Estimated H-index: 1
Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. We estimated the global prevalence, incidence, progression, and outcomes of NAFLD and nonalcoholic steatohepatitis (NASH). PubMed/MEDLINE were searched from 1989 to 2015 for terms involving epidemiology and progression of NAFLD. Exclusions included selected groups (studies that exclusively enrolled morbidly obese or diabetics or pediatric) and no data on alcohol consumption or other liver diseases. Incidence of...
Published on Jun 1, 2016in Gastroenterology 19.23
Quentin M. Anstee39
Estimated H-index: 39
(Newcastle University),
Devanshi Seth18
Estimated H-index: 18
(USYD: University of Sydney),
Christopher P. Day82
Estimated H-index: 82
(Newcastle University)
Genome-wide association studies and candidate gene studies have informed our understanding of factors contributing to the well-recognized interindividual variation in the progression and outcomes of alcoholic liver disease and nonalcoholic fatty liver disease. We discuss the mounting evidence for shared modifiers and common pathophysiological processes that contribute to development of both diseases. We discuss the functions of proteins encoded by risk variants of genes including patatin-like ph...
Published on Jun 1, 2016in Gastroenterology 19.23
Guillaume Lassailly9
Estimated H-index: 9
(French Institute of Health and Medical Research),
Robert Caiazzo25
Estimated H-index: 25
(French Institute of Health and Medical Research)
+ 1 AuthorsPhilippe Mathurin62
Estimated H-index: 62
(French Institute of Health and Medical Research)
It is important to provide treatment to patients with nonalcoholic steatohepatitis (NASH) because one third of patients with the metabolic syndrome die of liver disease. Basic research studies have elucidated mechanisms of NASH pathogenesis, which could lead to therapeutic targets. Health agencies have confirmed strategies for the optimal management of NASH and approved new drugs and treatments, which urgently are needed. The US Food and Drug Administration recently endorsed end points for NASH ...
Published on Jun 1, 2016in Current Hepatitis Reports
Lisa Beth VanWagner14
Estimated H-index: 14
(NU: Northwestern University),
Mary Eugenia Rinella24
Estimated H-index: 24
(NU: Northwestern University)
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide with an increased prevalence of metabolic, macro-, and microvascular complications. The primary causes of mortality in NAFLD are cardiovascular disease (CVD), malignancy, and liver disease. NAFLD is a multisystem disease that affects a variety of extrahepatic organ systems. The main focus of this review is to summarize the reported extrahepatic associations, which include CVD, chronic kidney dise...
Cited By95
Newest
Published on Dec 1, 2019in Scientific Reports 4.01
Yin-Yin Liao9
Estimated H-index: 9
(HK: Hungkuang University),
Chih-Kuang Yeh26
Estimated H-index: 26
(NTHU: National Tsing Hua University)
+ 2 AuthorsKuen-Cheh Yang7
Estimated H-index: 7
(NTU: National Taiwan University)
Nonalcoholic fatty liver disease (NAFLD) is an emerging epidemic worldwide and is regarded as a hepatic manifestation of metabolic syndrome (MetS). Only a few studies have discussed the biological features associated with quantitative assessment of ultrasound for characterizing NAFLD. Our aim was to delineate relevant metabolic characteristics using a new quantitative tool, the ultrasound quantitative diagnostic index (QDI). A total of 394 ultrasound data were analyzed to extract texture-feature...
Published in Nature Communications 11.88
Yuan Tian7
Estimated H-index: 7
(CAS: Chinese Academy of Sciences),
Bin Yang5
Estimated H-index: 5
(CAS: Chinese Academy of Sciences)
+ -3 AuthorsYao-cheng Rui ('SMMU': Second Military Medical University)
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome that elevates the risk of hepatocellular carcinoma (HCC). Although alteration of lipid metabolism has been increasingly recognized as a hallmark of cancer cells, the deregulated metabolic modulation of HCC cells in the NAFLD progression remains obscure. Here, we discovers an endoplasmic reticulum-residential protein, Nogo-B, as a highly expressed metabolic modulator in both murine and human NAFLD-ass...
Published on Feb 18, 2019in Cell Death & Differentiation 8.09
Isabel Schulien (University of Freiburg), Birgit Hockenjos6
Estimated H-index: 6
(University of Freiburg)
+ 4 AuthorsPeter Hasselblatt14
Estimated H-index: 14
(University of Freiburg)
Progression of non-alcoholic fatty liver disease (NAFLD) from steatosis to non-alcoholic steatohepatitis (NASH) is a key step of NASH pathogenesis. The AP-1 transcription factor c-Jun is an important regulator of hepatic stress responses, but its contribution to NASH pathogenesis remains poorly defined. We therefore addressed c-Jun expression in liver biopsies of patients with steatosis and NASH. The role of c-Jun during NASH pathogenesis was analyzed mechanistically in c-Jun mutant mice fed wit...
Published on Sep 1, 2019in Biomedicine & Pharmacotherapy 3.74
Xin Xin (SHU: Shanghai University), Cheng Chen2
Estimated H-index: 2
(SHU: Shanghai University)
+ 1 AuthorsQin Feng2
Estimated H-index: 2
(SHU: Shanghai University)
Abstract NAFLD is a vital health problem worldwide; however, no effective treatment is currently available for NAFLD. Intensive studies have indicated the efficacy of genistein (GE), a bioactive isoflavone extracted from soy, in treating NAFLD. In addition to its oestrogen-like effects, GE is known to have multiple molecular effects, for instance, lipid and glucose metabolism-promoting effects and activities against lipid peroxidation, inflammation, fibrosis, and NAFLD-related tumours. Here, thi...
Published on Jul 1, 2019in Toxicology and Applied Pharmacology 3.58
Takahiro Suga2
Estimated H-index: 2
(Tohoku University),
Hiroaki Yamaguchi18
Estimated H-index: 18
(Tohoku University)
+ 3 AuthorsMANONariyasu22
Estimated H-index: 22
(Tohoku University)
Abstract Non-alcoholic steatohepatitis (NASH) is a progressive inflammatory and fibrotic disease. However, the progression mechanism of NASH is not well understood. Bile acids are endogenous molecules that regulate cholesterol homeostasis, lipid solubilization in the intestinal lumen, and metabolic signaling via several receptors. In this study, we investigated the relationship between bile acid composition and NASH-associated fibrosis using a mouse model fed choline-deficient, L-amino-acid-defi...
Ben Murray2
Estimated H-index: 2
,
Lucía Barbier-Torres7
Estimated H-index: 7
+ -3 AuthorsShelly C. Lu57
Estimated H-index: 57
Published on Jun 20, 2019in Hepatology 14.97
Yutao Wang1
Estimated H-index: 1
(WHU: Wuhan University),
Huan Wen (WHU: Wuhan University)+ 14 AuthorsHan Tian (WHU: Wuhan University)
Maria João Meneses4
Estimated H-index: 4
,
Regina Silvestre + -3 AuthorsMaria Paula Macedo13
Estimated H-index: 13
Metabolic disorders are characterized by an overall state of inflammation and oxidative stress, which highlight the importance of a functional antioxidant system and normal activity of some endogenous enzymes, namely paraoxonase-1 (PON1). PON1 is an antioxidant and anti-inflammatory glycoprotein from the paraoxonases family. It is mainly expressed in the liver and secreted to the bloodstream, where it binds to HDL. Although it was first discovered due to its ability to hydrolyze paraoxon, it is ...
Published in Nature Reviews Immunology 44.02
Herbert Tilg71
Estimated H-index: 71
,
Niv Zmora14
Estimated H-index: 14
(Weizmann Institute of Science)
+ -3 AuthorsEran Elinav10
Estimated H-index: 10
(Weizmann Institute of Science)
Low-grade inflammation is the hallmark of metabolic disorders such as obesity, type 2 diabetes and nonalcoholic fatty liver disease. Emerging evidence indicates that these disorders are characterized by alterations in the intestinal microbiota composition and its metabolites, which translocate from the gut across a disrupted intestinal barrier to affect various metabolic organs, such as the liver and adipose tissue, thereby contributing to metabolic inflammation. Here, we discuss some of the rec...