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Increased Intrahepatic Mast Cell Density in Liver Cirrhosis Due to MASLD and Other Non-Infectious Chronic Liver
Nicolás Ortiz-López1,2, Araceli Pinto-León1, Javiera Favi1
1Laboratory of Immunogastroenterology I, Section of Gastroenterology, Department of Medicine, Hospital Clínico Universidad de Chile, Santiago 8380456, Chile.
Abstract:
Metabolic dysfunction-associated steatotic liver disease (MASLD) has become highly prevalent worldwide, and its pathogenesis and progression mechanisms remain incompletely understood. An increased activation of innate immune cells in the liver contributes to hepatic fibrogenesis via a chronic loop of inflammation and regeneration processes. Among them are mast cells (MCs), whose role in hepatic cirrhosis secondary to MASLD remains poorly studied. Our aim was to evaluate differences in MC density in cirrhotic liver tissue among patients with MASLD and other chronic liver disease etiologies. For this, a retrospective study of MC count was performed in cirrhotic liver explants obtained from MASLD, alcohol-related liver disease (ALD), and autoimmune hepatitis (AIH). We included a control group of subjects without liver damage. Tryptase-positive MCs were identified by indirect immunofluorescence and quantified as MC density per low-power field (MC/LPF). Group differences were analyzed using the Kruskal-Wallis test with Dunn's multiple comparisons, considering p < 0.05 as statistically significant. A significantly higher MC density was observed in MASLD, ALD, and AIH patients compared with the control group. The group analysis showed that ALD patients exhibited higher MC density than AIH, with no observed difference between ALD and MASLD. MC density was correlated positively with tobacco smoking and alcohol use in the full analyzed group, suggesting them as risk factors of high MC liver infiltration. We conclude that MC density is augmented in MASLD-related cirrhosis, highlighting potential links between lifestyle factors and MC-mediated hepatic inflammation. Future studies should explore the mechanisms driving this association and evaluate whether targeting MCs could help mitigate fibrosis progression.
Insights
Mast cells (MCs) are increased in liver cirrhosis, particularly in metabolic dysfunction-associated steatotic liver disease (MASLD). Lifestyle factors like smoking and alcohol correlate with higher MC density, suggesting a role in MASLD-related liver inflammation.
Area of Science:
- Hepatology
- Immunology
- Pathology
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health concern with unclear progression mechanisms.
- Innate immune cell activation, including mast cells (MCs), contributes to liver fibrosis through chronic inflammation and regeneration.
- The specific role of MCs in MASLD-related hepatic cirrhosis is not well understood.
Purpose of the Study:
- To compare mast cell (MC) density in cirrhotic liver tissue across different etiologies, focusing on MASLD.
- To investigate potential associations between MC density and lifestyle factors in chronic liver disease.
Main Methods:
- A retrospective analysis of cirrhotic liver explants from patients with MASLD, alcohol-related liver disease (ALD), and autoimmune hepatitis (AIH).
- Inclusion of a control group without liver damage.
- Identification and quantification of tryptase-positive MCs using indirect immunofluorescence (MC density per low-power field).
- Statistical analysis using Kruskal-Wallis test and Dunn's multiple comparisons (p < 0.05 significance).
Main Results:
- MC density was significantly higher in MASLD, ALD, and AIH patients compared to controls.
- ALD patients showed higher MC density than AIH patients; no significant difference was found between ALD and MASLD.
- MC density positively correlated with tobacco smoking and alcohol consumption in the overall study group.
Conclusions:
- MC density is elevated in MASLD-related liver cirrhosis.
- Findings suggest a link between lifestyle factors (smoking, alcohol) and increased MC infiltration in the liver.
- Further research is warranted to elucidate MC-mediated mechanisms in MASLD and explore MC-targeted therapies for fibrosis.
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