Inflammation may not be the key to fighting liver fibrosis in MAFLD

UCLA Health researchers have uncovered recent information about the role of inflammation in mitigating liver fibrosis, which is associated with metabolic fatty liver disease (MAFLD), one of the most common diseases in the world, affecting up to 40 percent of American adults. While inflammation in the liver has long been thought to be a prerequisite for the development of liver fibrosis, scarring and thickening of tissue that can impair the liver’s ability to function, recent research suggests that reducing inflammation may not affect the extent of fibrosis.

Liver fibrosis is a critical feature that causes chronic liver disease and liver cancer. If we can keep fibrosis under control, we can significantly impact liver disease.

Tamer Sallam, MD, PhD, corresponding author of the study, vice chair and associate professor, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles

He added: “For decades, we have believed that targeting inflammation was one of the most critical ways to reduce MAFLD. However, recent research suggests that inflammation, while still critical, may not be the primary driver of fibrosis.”

A study published in Journal of Clinical Research, looked specifically at a protein called lipopolysaccharide binding protein (LBP), which is involved in the body’s immune response, and how LBP works in mice. The results 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, researchers have also explored genetic analyses of vast human data sets and human tissue samples from MAFLD patients at different stages of the disease to investigate the consequences of LBP loss of function. The cumulative evidence has shown that LBP does not alter scar tissue markers.

Sallam pointed out the need for further research into the effect of LBP on inflammation and whether other factors might provide more effective reduction in inflammation and have an impact on reducing fibrosis.

“Reducing scar tissue burden is one of the holy grails in treating advanced liver disease,” Sallam said. “These results suggest that certain treatments for inflammation may not be viable options and that more targeted therapies against other pathways may facilitate us better treat fibrosis and improve patient outcomes.”