Hepatic Mac2-BP expression depends on liver fibrosis and inflammation due to fat accumulation in patients with metabolic dysfunction-associated steatotic liver disease.

Abstract

Data on the upregulation of Mac-2 binding protein (M2BP) expression associated with fat accumulation in the liver are limited. Therefore, we aimed to assess the relationship between hepatic M2BP expression and changes in the liver microenvironment due to fat accumulation in patients with metabolic dysfunction associated steatotic liver disease (MASLD). Liver specimens obtained from 46 patients with MASLD were subjected to immunohistochemical staining to visualize M2BP expression in the liver. The staining intensity in the hepatocytes and sinusoidal cells was classified as high or low grade. First, the correlation between hepatic M2BP expression and microenvironmental changes caused by fat accumulation was examined. Then, the influence of hepatic M2BP expression on serum M2BP glycosylation isomer levels in patients with MASLD was evaluated. The staining grade of M2BP was higher in the sinusoidal cells than in the hepatocytes (p=0.015). The patients with high staining grade in their hepatocytes had more severe lobular inflammation than those with low staining grade (p=0.037). Additionally, the patients with high staining grade in their sinusoidal cells presented more severe fibrosis than those with low staining grade (p=0.018). The staining grade in the hepatocytes correlated positively with serum M2BP glycosylation isomer levels (p=0.023), whereas no correlation was observed between sinusoidal staining grade and serum M2BP glycosylation isomer levels (p=0.393). Fat accumulation in patients with MASLD leads to M2BP expression in hepatocytes due to liver inflammation and that in sinusoidal cells due to fibrosis.