Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases.
Key physiological functions of the liver, including glucose and lipid metabolism, become disturbed in the setting of non-alcoholic fatty liver disease (NAFLD) and may be associated with a systemic inflammatory 'milieu' initiated in part by liver-secreted cytokines and molecules. Consequently, the pathophysiological effects of NAFLD extend beyond the liver with a large body of clinical evidence demonstrating NAFLD to be independently associated with both prevalent and incident cardiovascular disease (CVD), chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). The magnitude of risk of developing these extrahepatic diseases parallels the underlying severity of NAFLD, such that patients with non-alcoholic steatohepatitis (NASH) appear to be at greater risk of incident CVD, CKD and T2DM than those with simple steatosis. Other modifiers of risk may include genetic variants (eg, patatin-like phospholipase domain-containing 3 and trans-membrane 6 superfamily member 2 polymorphisms), visceral adipose tissue accumulation, dietary intake and the gut microbiome. Emerging data also suggest that NAFLD may be a risk factor for colonic neoplasia and reduced bone mineral density, especially among men. Importantly, improvement/resolution of NAFLD is associated with a reduced incidence of T2DM and improved kidney function, adding weight to causality and suggesting liver focused treatments may reduce risk of extrahepatic complications. Awareness of these associations is important for the clinicians such that CVD risk factor management, screening for T2DM and CKD are part of the routine management of patients with NAFLD.
School of Medicine and Pharmacology, The University of Western Australia, Nedlands, Western Australia, Australia.
Leon A
LA
Adams
Faculty of Medical Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK.|Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, UK.
Quentin M
QM
Anstee
Department of Internal Medicine I, Gastroenterology, Hepatology & Metabolism, Medical University Innsbruck, Innsbruck, Austria.
Herbert
H
Tilg
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
Giovanni
G
Targher
D054392:Adipokines / Q000378:metabolism; D000818:Animals; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000209:etiology; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000209:etiology; D016207:Cytokines / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000209:etiology; D004032:Diet; D000069196:Gastrointestinal Microbiome; D006801:Humans; D015994:Incidence; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000503:physiopathology*; D009752:Nutritional Status; D010024:Osteoporosis / Q000453:epidemiology* / Q000209:etiology; D015995:Prevalence; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology* / Q000209:etiology; D012307:Risk Factors
D054392:Adipokines; D016207:Cytokines
CARDIOVASCULAR DISEASE; DIABETES MELLITUS; NONALCOHOLIC STEATOHEPATITIS