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Lean NAFLD: an underrecognized and challenging disorder in medicine

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Abstract

Classically, Non-Alcoholic Fatty Liver Disease (NAFLD) has been thought to be driven by excessive weight gain and obesity. The overall greater awareness of this disorder has led to its recognition in patients with normal body mass index (BMI). Ongoing research has helped to better understand potential causes of Lean NAFLD, the risks for more advanced disease, and potential therapies. Here we review the recent literature on prevalence, risk factors, severity of disease, and potential therapeutic interventions.

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Abbreviations

NAFLD:

Non-Alcoholic Fatty Liver Disease

BMI:

body mass index

BMI:

body mass index

MetS:

metabolic syndrome

MAFLD:

Metabolic Associated Fatty Liver Disease

T2DM:

type 2 diabetes

NASH:

Non-alcoholic steatohepatitis

WHO:

World Health Organization

AACE:

Association of Clinical Endocrinologists

FFA:

free fatty acids

PNPLA3:

patatin-like phospholipasedomain-containing 3

TM6SF2:

transmembrane 6-superfamily member 2

DAG:

diacylglyceral

di-PPA:

di-palmitoyl phosphatidic acid

AASLD:

American Association for the Study of Liver Disease

EASL:

European Association for the Study of Liver

EASD:

European Association for the Study of Diabetes

EASO:

European Association for the Study of Obesity

ADA:

American Diabetes Association

APASL:

Asian Pacific Association for the Study of the Liver

ALT:

Alanine transaminase

FLI:

fatty liver index

HCV:

hepatitis C

ACG:

American College of Gastroenterology

HFCS:

high fructose corn syrup

NHANES:

National Health and Nutrition Examination Survey

FIB-4:

fibrosis-4 index

NFS:

NAFLD fibrosis score

ATP:

adenosine triphosphate

LPS:

Lipopolysaccharide

TASH:

toxicant-associated steatohepatitis

HCC:

hepatocellular carcinoma

HSD17B13:

hydroxysteroid 17-beta dehydrogenase 13

CETP:

Cholesteryl Ester Transfer Protein

SREBF:

Sterol regulatory element-binding factor

GCKR:

Glucokinase Regulatory Protein

LFT:

liver function test

US:

ultrasound

DEXA:

Dual-energy X-ray absorptiometry

CAP:

Controlled Attenuation Parameter

TZD:

thiazolidinediones

(GLP-1) agonists:

glucagon like-peptide-1

DPP-4:

Dipeptidyl peptidase 4

DNL:

De novo Lipogenesis

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Authors and Affiliations

  1. Division of Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA

    Sheila Maier & Thomas Jensen

  2. Division of Hepatology, University of Colorado School of Medicine, Aurora, CO, USA

    Amanda Wieland

  3. Division of Pediatric Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA

    Melanie Cree-Green & Kristen Nadeau

  4. Division of Gastroenterology, University of Colorado School of Medicine, Aurora, CO, USA

    Shelby Sullivan

  5. Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, CO, USA

    Miguel A. Lanaspa & Richard J. Johnson

  6. Division of Endocrinology, University of Colorado, Denver, Denver, CO, USA

    Thomas Jensen

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SM, AW, MCG, KN, SS, and TJ have no conflicts of interest to report. RJ and ML have equity with Colorado Research Partners LLC that is developing inhibitors of fructose metabolism. RJ also has equity with XORTX Therapeutics that is developing novel xanthine oxidase inhibitors. RJ also has consulted for Astra Zeneca and Horizon Pharma. RJ and ML are inventors on several patents and patent applications related to fructose metabolism.

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Maier, S., Wieland, A., Cree-Green, M. et al. Lean NAFLD: an underrecognized and challenging disorder in medicine. Rev Endocr Metab Disord 22, 351–366 (2021). https://doi.org/10.1007/s11154-020-09621-1

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