Intestinal permeability and immune-inflammatory markers in patients with idiosyncratic drug-induced liver injury, drug induced steatosis and metabolic dysfunction–associated steatotic liver disease (MASLD)

Abstract

Background and Purpose

Adverse immuno-inflammatory responses possibly influenced by bacterial compounds reaching the liver as a consequence of altered intestinal permeability appear to be crucial in the pathogenesis of drug-induced liver injury and steatotic liver diseases. This study aimed to assess intestinal permeability and immuno-inflammatory status in patients by measuring indirect biomarkers. Experimental Approach

Circulating marker levels were measured in serum and plasma samples of 36 healthy controls, 32 patients with drug-induced liver injury, 14 with autoimmune hepatitis, 13 with viral hepatitis, 40 with metabolic dysfunction–associated steatotic liver disease (MASLD) and 16 with drug-induced steatosis. All patients with acute liver injury were identified (visit 1) and followed for >30 days (visit 2). Correlation analyses were performed to determine potential associations. Key Results

Drug-induced liver injury, autoimmune hepatitis and viral hepatitis patients had higher levels of LBP, CD14, CD163, MCSF-1R (CSFR) and ICAM-1 and significantly lower levels of MAdCAM-1 and zonulin at detection of liver injury compared with healthy controls or the second visit. Drug-induced steatosis and MASLD patients had increased levels of S100A9, S100A12 and zonulin. MASLD patients with significant fibrosis (F2–F4) also had higher levels of CD163 and MCSF-1R. No difference was found between drug-induced steatosis and MASLD with no or low fibrosis. Conclusion and Implications

Our results highlight similarities in macrophage activation, intestinal barrier dysfunction and translocation of bacterial products in liver injury of various aetiologies. A better understanding of the pathophysiological mechanisms may aid the development of targeted therapies for liver inflammation and fibrosis.