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Abstract Details
Nonalcoholic fatty liver disease (NAFLD) from pathogenesis to treatment concepts in humans
Mol Metab. 2021 Aug;50:101122. doi: 10.1016/j.molmet.2020.101122.Epub 2020 Nov 19.
Kalliopi Pafili1, Michael Roden2
Author information
1Institute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Düsseldorf, Germany; German Center for Diabetes Research, München-Neuherberg, Germany.
2Institute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Düsseldorf, Germany; German Center for Diabetes Research, München-Neuherberg, Germany; Division of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany. Electronic address: michael.roden@ddz.de.
Abstract
Background: Nonalcoholic fatty liver disease (NAFLD) comprises hepatic alterations with increased lipid accumulation (steatosis) without or with inflammation (nonalcoholic steatohepatitis, NASH) and/or fibrosis in the absence of other causes of liver disease. NAFLD is developing as a burgeoning health challenge, mainly due to the worldwide obesity and diabetes epidemics.
Scope of review: This review summarizes the knowledge on the pathogenesis underlying NAFLD by focusing on studies in humans and on hypercaloric nutrition, including effects of saturated fat and fructose, as well as adipose tissue dysfunction, leading to hepatic lipotoxicity, abnormal mitochondrial function, and oxidative stress, and highlights intestinal dysbiosis. These mechanisms are discussed in the context of current treatments targeting metabolic pathways and the results of related clinical trials.
Major conclusions: Recent studies have provided evidence that certain conditions, for example, the severe insulin-resistant diabetes (SIRD) subgroup (cluster) and the presence of an increasing number of gene variants, seem to predispose for excessive risk of NAFLD and its accelerated progression. Recent clinical trials have been frequently unsuccessful in halting or preventing NAFLD progression, perhaps partly due to including unselected cohorts in later stages of NAFLD. On the basis of this literature review, this study proposed screening in individuals with the highest genetic or acquired risk of disease progression, for example, the SIRD subgroup, and developing treatment concepts targeting the earliest pathophysiolgical alterations, namely, adipocyte dysfunction and insulin resistance.