Macrophages and platelets in liver fibrosis and hepatocellular carcinoma

Abstract

During fibrosis, (myo)fibroblasts deposit large amounts of extracellular matrix proteins, thereby replacing healthy functional tissue. In liver fibrosis, this leads to the loss of hepatocyte function, portal hypertension, variceal bleeding, and increased susceptibility to infection. At an early stage, liver fibrosis is a dynamic and reversible process, however, from the cirrhotic stage, there is significant progression to hepatocellular carcinoma. Both liver-resident macrophages (Kupffer cells) and monocyte-derived macrophages are important drivers of fibrosis progression, but can also induce its regression once triggers of chronic inflammation are eliminated. In liver cancer, they are attracted to the tumor site to become tumor-associated macrophages (TAMs) polarized towards a M2- anti-inflammatory/tumor-promoting phenotype. Besides their role in thrombosis and hemostasis, platelets can also stimulate fibrosis and tumor development by secreting profibrogenic factors and regulating the innate immune response, e.g., by interacting with monocytes and macrophages. Here, we review recent literature on the role of macrophages and platelets and their interplay in liver fibrosis and hepatocellular carcinoma.

Can Nutraceuticals Support the Treatment of MASLD/MASH, and thus Affect the Process of Liver Fibrosis?

“…Some researchers indicate that KCs show the ability to initiate and progress MASH (metabolic dysfunction-associated steatohepatitis) [30,31]. During inflammation, both monocyte-derived macrophages and KCs show the expression of pro-inflammatory cytokines, i.e., TNFα (tumor necrosis factor alpha), IL-6 (interleukin 6), and chemokines, e.g., CCL2 (C-C motif chemokine ligand 2), which consequently exacerbate inflammation through the influx of macrophages from monocytes [14]. Activated macrophages secrete TGFβ1, which is a major cytokine that induces fibrinogenesis in activated myofibroblasts and stellate cells [32].…”

“…Therefore, the purpose of our review is to delve into the role of The process of liver fibrosis is complex and depends on many factors. Damage to normal liver tissue results in the accumulation of ECM proteins, and this is mainly crosslinked interstitial collagen (types I, III, and VI), basement membrane collagen (type IV), and other proteins [13,14]. The liver cells (hepatocytes) themselves can be damaged by metabolic, toxic, or viral factors [15].…”