Role of Perturbated Hemostasis in MASLD and Its Correlation with Adipokines

Abstract

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise, making it one of the most prevalent chronic liver disorders. MASLD encompasses a range of liver pathologies, from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) with inflammation, hepatocyte damage, and fibrosis. Interestingly, the liver exhibits close intercommunication with fatty tissue. In fact, adipose tissue could contribute to the etiology and advancement of MASLD, acting as an endocrine organ that releases several hormones and cytokines, with the adipokines assuming a pivotal role. The levels of adipokines in the blood are altered in people with MASLD, and recent research has shed light on the crucial role played by adipokines in regulating energy expenditure, inflammation, and fibrosis in MASLD. However, MASLD disease is a multifaceted condition that affects various aspects of health beyond liver function, including its impact on hemostasis. The alterations in coagulation mechanisms and endothelial and platelet functions may play a role in the increased vulnerability and severity of MASLD. Therefore, more attention is being given to imbalanced adipokines as causative agents in causing disturbances in hemostasis in MASLD. Metabolic inflammation and hepatic injury are fundamental components of MASLD, and the interrelation between these biological components and the hemostasis pathway is delineated by reciprocal influences, as well as the induction of alterations. Adipokines have the potential to serve as the shared elements within this complex interrelationship. The objective of this review is to thoroughly examine the existing scientific knowledge on the impairment of hemostasis in MASLD and its connection with adipokines, with the aim of enhancing our comprehension of the disease.

Keywords: MASLD; NAFLD; adipokines; coagulation; dysfunctional hemostasis; endothelium; inflammation; insulin resistance; platelet.

Figure 1

MASLD, hemostasis, and adipokines. Patients with MASLD have modifications in the physiological process of hemostasis. Adipokines, principally produced by the adipose tissue, could play a significant role in the pathogenesis of MASLD and could contribute to the disruption of hemostasis. Created with https://BioRender.com (accessed on 27 November 2023); MASLD: metabolic dysfunction-associated steatotic liver disease.

Figure 2

A simplified diagram illustrating the process of hemostasis. Hemostasis is a complex physiological process that relies heavily on the intricate interplay between coagulation factors that facilitate clot formation and those that promote clot dissolution. The maintenance of this delicate equilibrium is of paramount importance for the prevention of excessive bleeding or thrombosis and thus forms a critical aspect of the clinical management of many medical conditions. Created with https://BioRender.com (accessed on 29 November 2023).

Figure 3

Dysfunctional hemostasis in MASLD. The pathophysiology of MASLD encompasses a complex interplay of various mechanisms, including coagulation abnormalities and platelet and endothelial dysfunction, which collectively contribute to the dysregulation of hemostasis in MASLD individuals. Severe manifestations of MASLD are more likely to occur in individuals with COVID-19, in which hemostasis disruptions appear to play a significant role. Given that liver malfunctioning is a common disturbance between the two diseases, it is possible that the coexistence of COVID-19 disease, which is also distinguished by hemostasis alterations, could exacerbate the hemostatic dysfunction of individuals with MASLD. Created with https://BioRender.com (accessed on 27 November 2023) and modified with Microsoft PowerPoint v.16; MASLD: metabolic dysfunction-associated steatotic liver disease.

Figure 4

Circuit of perturbed hemostasis. Metabolic inflammation and liver injury are integral components of MASLD. The intricate interplay between these components and the hemostasis is distinguished by mutual influences and the elicitation of alterations. Adipokines have the potential to function as the common factors within this intricate association. Adiponectin and ghrelin (circles in green) have a favorable impact on MASLD’s pathogenesis and hemostasis, while adipose tissue-derived plasminogen inhibitor-1, leptin, and resistin (circles in red) have a detrimental effect on MASLD. Created with https://BioRender.com (accessed on 27 November 2023); MASLD: metabolic dysfunction-associated steatotic liver disease.