High-Risk Groups for Non-alcoholic Fatty Liver and Non-alcoholic Steatohepatitis Development and Progression
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FATTY LIVER DISEASE (V AJMERA, SECTION EDITOR)
High-Risk Groups for Non-alcoholic Fatty Liver and Non-alcoholic Steatohepatitis Development and Progression Yedidya Saiman 1 & Royce Hooks 1 & Rotonya M. Carr 1
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review This paper reviews the pathophysiology of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH) development and the clinical and genetic risk factors associated with its progression. Recent Findings Lipotoxicity underlies the development and progression of NAFLD/NASH. Obesity, insulin resistance, metabolic syndrome, ethnicity, and genetics are associated with the severity and progression of NAFLD/NASH. Summary Personalized approaches to NAFLD/NASH management should take these “high-risk” categories of NAFLD/NASH progression into account in order to reduce NAFLD/NASH-associated morbidity and mortality. Keywords NAFLD . NASH . NASH progression . Obesity . Genetics . Lipotoxicity
Introduction
NASH Development and Progression
Non-alcoholic fatty liver disease (NAFLD) is a systemic metabolic disease with hepatic manifestations. NAFLD is currently the most common cause of liver disease worldwide and is estimated to affect 30% of US adults; 24% of Europeans; 30% of South Americans; 32% of Middle Eastern populations; 27% of Asians; and 13% of Africans [1–3]. In the liver, NAFLD evolves from simple steatosis (non-alcoholic fatty liver (NAFL)) to non-alcoholic steatohepatitis (NASH). NASH can progress to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Both the promotion of NASH and the pace of its progression are impacted by a myriad of factors. These include the following: metabolic, genetic, microbial, behavioral, and environmental influences. Here, we review the mechanisms by which these factors promote NASH and NASH progression.
Development
This article is part of the Topical Collection on Fatty Liver Disease * Rotonya M. Carr [email protected] 1
Perelman School of Medicine, Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA, USA
NASH is defined histologically by the presence of the ballooned hepatocyte on liver biopsy or clinically by symptoms of end-stage liver disease in an individual with NAFLD. NASH fibrosis is staged from stage 0 (no fibrosis) to stage 4 fibrosis (cirrhosis). While fibrosis is the most significant histologic factor that predicts liver-related morbidity and mortality, steatosis (the other salient feature of earlier stage NASH) predicts cardiometabolic consequences [4]. The specific events that trigger the transition from NAFL to NASH are unknown; however, one likely inciting event is the hepatocellular accumulation of lipotoxic, bioactive lipids. Lipotoxic lipids alter cellular and membrane structure and function, promote oxidative stress, provoke inflammatory cascades, and, in some cases, cause apoptotic cellular death [5]. Consistent with this mechanism is that the ballooned hepatocyte is characterized by lipid drop
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