The “Domino effect” in MASLD: The inflammatory cascade of steatohepatitis

Mladenić, Karlo; Lenartić, Maja; Marinović, Sonja; Polić, Bojan; Wensveen, Felix Martinus (2024) The “Domino effect” in MASLD: The inflammatory cascade of steatohepatitis. European Journal of Immunology, 54 (4). ISSN 0014-2980

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Abstract

Metabolic dysfunction‐associated steatotic liver disease (MASLD) is an increasingly common complication of obesity, affecting over a quarter of the global adult population. A key event in the pathophysiology of MASLD is the development of metabolic‐associated steatohepatitis (MASH), which greatly increases the chances of developing cirrhosis and hepatocellular carcinoma. The underlying cause of MASH is multifactorial, but accumulating evidence indicates that the inflammatory process in the hepatic microenvironment typically follows a pattern that can be roughly divided into three stages: (1) Detection of hepatocyte stress by tissue‐resident immune cells including γδ T cells and CD4−CD8− double‐negative T cells, followed by their secretion of pro‐inflammatory mediators, most notably IL‐17A. (2) Recruitment of pro‐inflammatory cells, mostly of the myeloid lineage, and initiation of inflammation through secretion of effector‐type cytokines such as TNF, TGF‐β, and IL‐1β. (3) Escalation of the inflammatory response by recruitment of lymphocytes including Th17, CD8 T, and B cells leading to chronic inflammation, hepatic stellate cell activation, and fibrosis. Here we will discuss these three stages and how they are consecutively linked like falling domino tiles to the pathophysiology of MASH. Moreover, we will highlight the clinical potential of inflammation as a biomarker and therapeutic target for the treatment of MASLD.

Item Type:	Article
Uncontrolled Keywords:	cytokines; fibrosis; hepatocytes; immune cells; Inflammation; MAFLD; NASH; NAFLD; T cells; MASLD
Subjects:	BIOMEDICINE AND HEALTHCARE BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences > Immunology
Divisions:	Division of Molecular Medicine
Projects:	Project title Project leader Project code Project type Uloga stanica urođene imunosti u razvoju nealkoholnog steatohepatitisa (NASH) i fibroze jetre- Bojan Polić uniri-biomed-18-89 NadSve Imunosni mehanizmi u razvoju upale i metaboličkog sindroma u debljini-INFLAMETAB Bojan Polić IP-2016-06-9306 HRZZ Mehanizmi imunološkog prepoznavanja u jetri i njihova uloga u razvoju nealkoholnog steatohepatitisa-MITRAS Bojan Polić IPCH-2020-10-8440 HRZZ
Depositing User:	Sonja Marinović
Date Deposited:	12 Dec 2025 07:11
URI:	http://fulir.irb.hr/id/eprint/10402
DOI:	10.1002/eji.202149641

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