Chronic Inflammation in Non-Alcoholic Steatohepatitis: Molecular Mechanisms and Therapeutic Strategies

Abstract

Non-Alcoholic Steatohepatitis (NASH) is the progressive form of Non-Alcoholic Fatty Liver Disease (NAFLD), the main cause of chronic liver complications. The development of NASH is the consequence of aberrant activation of hepatic conventional immune, parenchymal, and endothelial cells in response to inflammatory mediators from the liver, adipose tissue, and gut. Hepatocytes, Kupffer cells and liver sinusoidal endothelial cells contribute to the significant accumulation of bone-marrow derived-macrophages and neutrophils in the liver, a hallmark of NASH. The aberrant activation of these immune cells elicits harmful inflammation and liver injury, leading to NASH progression. In this review, we highlight the processes triggering the recruitment and/or activation of hepatic innate immune cells, with a focus on macrophages, neutrophils, and innate lymphoid cells as well as the contribution of hepatocytes and endothelial cells in driving liver inflammation/fibrosis. On-going studies and preliminary results from global and specific therapeutic strategies to manage this NASH-related inflammation will also be discussed.

Scolymus hispanicus (Golden Thistle) Ameliorates Hepatic Steatosis and Metabolic Syndrome by Reducing Lipid Accumulation, Oxidative Stress, and Inflammation in Rats under Hyperfatty Diet

“…e intake will be higher and the storage lipids will therefore be increased. e increase in the storage of lipids and lipid derivatives leads to the expansion of adipose tissue (hyperplasia and hypertrophy) and the installation of lipotoxicity, which has harmful effects resulting in nonalcoholic fatty liver disease (NAFLD), which is associated with obesity [2].…”

“…NAFLD was recently redefined as metabolic-associated fatty liver disease (MAFLD) to reflect better the pathogenesis [2]. NAFLD is the most common chronic liver disease that affects around 25% of the population.…”

“…NAFLD encompasses a broad spectrum of diseases that include simple fatty infiltration nonalcoholic steatohepatitis (NASH), which is defined as the presence of fat leading to inflammatory damage to hepatocytes, fibrosis, and finally cirrhosis. e importance of NAFLD lies in the possibility of its gradual progress to advanced fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) [2,3]. e overall prevalence of NAFLD is growing in parallel with the global epidemic of obesity [4].…”

“…Abdominal fat overage is a fundamental determinant in NAFLD pathogenesis due to its association with IR and a possible source of free fatty acids (FFA) [3,6]. Trunk fat was found to be indicative of elevated ALT, supporting the potential involvement of the metabolically active intra-abdominal fat in increased liver injury [2].…”

“…Obesity is associated with an increase in adipose tissue lipolysis, secretion of inflammatory, and fibrotic mediators, which can reach the liver. e accumulation of inflammatory/immune cells and the modification of the activities of these cells in the adipose tissue contributed to chronic lowgrade inflammation during obesity [2,3].…”