Study Reveals Inflammation Targeting Ineffective for Reducing Liver Fibrosis in MAFLD

A study published in the Journal of Clinical Investigation uncovered new information about the role inflammation plays in mitigating liver fibrosis, which is associated with metabolic-associated fatty liver disease (MAFLD), one of the most common diseases in the world affecting up to 40 percent of the adults. While inflammation in the liver has long been considered a prerequisite to developing liver fibrosis, the scarring and thickening of tissue that can impair the liver’s ability to function, this new research suggested that reducing inflammation may not influence the extent of fibrosis.

The study looked specifically at a protein called lipopolysaccharide binding protein (LBP), which is involved in the body's immune response, and how LBP functions in mice. Findings showed that mice without LBP in their liver cells had lower levels of liver inflammation and better liver function but no change in fibrosis.

In addition to mouse models, the researchers also studied genetic analyses from large human datasets and human tissue samples from MAFLD patients at different stages in the disease, to examine the consequence of loss of LBP function. The evidence combined showed that the LBP does not alter scar tissue markers.

Researchers indicated a need to further explore how LBP influences inflammation and whether other factors can offer a more potent reduction in inflammation and have an impact on reducing fibrosis.

This study suggested that targeting inflammation may not be effective in reducing liver fibrosis in individuals with Metabolic Associated Fatty Liver Disease (MAFLD).

Despite inflammation being a known contributor to liver damage, the study’s findings indicated that therapies aimed at mitigating inflammation alone might not significantly improve fibrosis outcomes. This underscored the need for alternative or complementary strategies to address liver fibrosis in MAFLD, potentially focusing on other pathways or mechanisms involved in the disease's progression.

Reference: Dan Wang, Jihane N. Benhammou, Tamer Sallam; Hepatic lipopolysaccharide binding protein partially uncouples inflammation from fibrosis in MAFLD; J Clin Invest. 2024. https://doi.org/10.1172/JCI179752.