Analysis of Common Pathways and Markers From Non-Alcoholic Fatty Liver Disease to Immune-Mediated Diseases

Abstract

Metabolic associated fatty liver disease (MAFLD) is the most prevalent form of liver disease worldwide, accounting for a high liver-related mortality and morbidity with extensive multi-organ involvement. This entity has displaced viral hepatitis as the main cause of severe forms of hepatic diseases, although the onset and transition of MAFLD stages still remains unclear. Nevertheless, innate and adaptive immune responses seem to play an essential role in the establishment and further progression of this disease. The immune system is responsible of safeguard and preserves organs and systems function, and might be altered under different stimuli. Thus, the liver suffers from metabolic and immune changes leading to different injuries and loss of function. It has been stablished that cell-cell crosstalk is a key process in the hepatic homeostasis maintenance. There is mounting evidence suggesting that MAFLD pathogenesis is determined by a complex interaction of environmental, genetic and host factors that leads to a full plethora of outcomes. Therefore, herein we will revisit and discuss the interplay between immune mechanisms and MAFLD, highlighting the potential role of immunological markers in an attempt to clarify its relationship.

PD-1/PD-L1 Immuno-Mediated Therapy in NAFLD: Advantages and Obstacles in the Treatment of Advanced Disease

“…Patients with NAFLD with pronounced intestinal inflammation show decreased numbers of CD4+ and CD8+ T lymphocytes in the intestinal mucosa, associated with increased cytokine secretion and disruption of tight junctions [ 14 ]. Lipopolysaccharide (LPS), a PAMP which activates TLR4 signaling, induces liver inflammation triggering the production of tumor necrosis factors by liver macrophages and participates in the development of hepatic fibrosis [ 41 ]. Moreover, it has been previously demonstrated that the response of colonic myofibroblasts (CMFs) to the bacterial PAMPs may favor a suppressive effect on activated CD4+ T cells in the colonic mucosa via upregulation of negative co-stimulator PD-L1 mainly through TLR2, 4, and/or TLR5.…”

Emerging pharmacological treatment options for MAFLD

“…Fat hepatocyte injury increases several mechanisms of hepatic inflammation driving the progression of MAFLD and thus are under-studied as new targets for MAFLD. 53 …”

The protective roles of augmenter of liver regeneration in hepatocytes in the non-alcoholic fatty liver disease

“…With economic growth and changing lifestyles, the prevalence of NAFLD has increased rapidly to become a global burden. NAFLD occurs in 25% of the general population, especially in developed countries ( Younossi et al, 2016 ; Cotter and Rinella, 2020 ; Gallego-Duran et al, 2021 ). It is estimated that the annual incidence of hepatocellular carcinoma is between 0.5% and 2.6% in patients with NAFLD and cirrhosis ( Huang et al, 2021a ).…”