US EPA

5932818 

Journal Article 

The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis 

Kazankov, K; Jørgensen, S; Thomsen, K.L.; Møller, HJ; Vilstrup, H; George, J; Schuppan, D; Grønbæk, H 

2018 

1 

Nature Reviews. Gastroenterology & Hepatology
ISSN: 1759-5045
EISSN: 1759-5053 

16 

3 

145-159 

English 

30482910 

10.1038/s41575-018-0082-x 

Nonalcoholic fatty liver disease (NAFLD) and its inflammatory and often progressive subtype nonalcoholic steatohepatitis (NASH) are becoming the leading cause of liver-related morbidity and mortality worldwide, and a primary indication for liver transplantation. The pathophysiology of NASH is multifactorial and not yet completely understood; however, innate immunity is a major contributing factor in which liver-resident macrophages (Kupffer cells) and recruited macrophages play a central part in disease progression. In this Review, we assess the evidence for macrophage involvement in the development of steatosis, inflammation and fibrosis in NASH. In this process, not only the polarization of liver macrophages towards a pro-inflammatory phenotype is important, but adipose tissue macrophages, especially in the visceral compartment, also contribute to disease severity and insulin resistance. Macrophage activation is mediated by factors such as endotoxins and translocated bacteria owing to increased intestinal permeability, factors released from damaged or lipoapoptotic hepatocytes, as well as alterations in gut microbiota and defined nutritional components, including certain free fatty acids, cholesterol and their metabolites. Reflecting the important role of macrophages in NASH, we also review studies investigating drugs that target macrophage recruitment to the liver, macrophage polarization and their inflammatory effects as potential treatment options for patients with NASH.