From complement to complosome in non‐alcoholic fatty liver disease: when location matters

Nguyen, Van Dien, Hughes, Timothy R. ORCID: https://orcid.org/0000-0003-2348-3490 and Zhou, You ORCID: https://orcid.org/0000-0002-1743-1291 2024. From complement to complosome in non‐alcoholic fatty liver disease: when location matters. Liver International 44 (2) , pp. 316-329. 10.1111/liv.15796

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Abstract

Non‐alcoholic fatty liver disease (NAFLD) is a growing public health threat and becoming the leading cause of liver transplantation. Nevertheless, no approved specific treatment is currently available for NAFLD. The pathogenesis of NAFLD is multifaceted and not yet fully understood. Accumulating evidence suggests a significant role of the complement system in the development and progression of NAFLD. Here, we provide an overview of the complement system, incorporating the novel concept of complosome, and summarise the up‐to‐date evidence elucidating the association between complement dysregulation and the pathogenesis of NAFLD. In this process, the extracellular complement system is activated through various pathways, thereby directly contributing to, or working together with other immune cells in the disease development and progression. We also introduce the complosome and assess the evidence that implicates its potential influence in NAFLD through its direct impact on hepatocytes or non‐parenchymal liver cells. Additionally, we expound upon how complement system and the complosome may exert their effects in relation with hepatic zonation in NAFLD. Furthermore, we discuss the potential therapeutic implications of targeting the complement system, extracellularly and intracellularly, for NAFLD treatment. Finally, we present future perspectives towards a better understanding of the complement system's contribution to NAFLD.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/
Publisher:	Wiley
ISSN:	1478-3223
Date of First Compliant Deposit:	28 November 2023
Date of Acceptance:	9 November 2023
Last Modified:	20 Feb 2024 15:01
URI:	https://orca.cardiff.ac.uk/id/eprint/164427

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