title: Obesity, insulin resistance, NASH and hepatocellular carcinoma.
abstract: Epidemiological and clinical data have clearly demonstrated that non-alcoholic steatohepatitis (NASH) predisposes risk to the development of hepatocellular carcinoma (HCC). NASH is the liver manifestation of metabolic syndrome, which constellates obesity, insulin resistance and dyslipidemia. Although the percentage of patients diagnosed annually with NASH-associated HCC is still relatively low, this number signifies a large population due to the rapidly increasing incidence of obesity and diabetes globally. Fundamental studies on lipid storage, regulation of adipose factors, inflammatory cytokine recruitments and oxidative stress have provided insights into NASH as well as metabolic syndrome. Recent evidence also indicates the significant role of genetic factors in contributing to the pathogenesis of NASH and induced hepatic malignancy. In this review, we attempt to collate current research on NASH biology that lead to our understandings on how metabolic disorders may intersect with cancer development. We also discuss study models that have supported discoveries of molecular and cellular defects, and offered a perspective on therapeutic developments. These studies have collectively increased our knowledge on the complex signaling pathways involved in NASH and cancer, and provided the foundation for improved clinical management of patients with metabolic diseases.
authors.affiliation: Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China. Electronic address: junyu@cuhk.edu.hk.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Jiayun
authors.initials: J
authors.lastname: Shen
authors.forename: Ting Ting
authors.initials: TT
authors.lastname: Sun
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.forename: Nathalie
authors.initials: N
authors.lastname: Wong
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D005234:Fatty Liver / Q000150:complications* / Q000209:etiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000209:etiology*; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000150:complications*; D012307:Risk Factors; D015398:Signal Transduction
chemical_list: D015415:Biomarkers
keywords: Hepatocellular carcinoma; Insulin resistance; Metabolic syndrome; NASH; Obesity