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).

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.