UCLA Health researchers have discovered 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 American adults. While inflammation in the liver has long been considered a prerequisite for the development of liver fibrosis — scarring and thickening of tissue that can impair the liver’s ability to function — this new research suggests that reducing inflammation may not influence the extent of fibrosis.
“Liver fibrosis is the critical feature that drives chronic liver disease and liver cancer. If we can keep fibrosis under control, we can have a significant impact on liver disease,” said Dr. Tamer Sallam, corresponding author of the study and vice chair and associate professor in the Department of Medicine at the David Geffen School of Medicine at UCLA.
“For decades we have believed that targeting inflammation is one of the most important ways to reduce MAFLD. But this new research indicates that inflammation, while still important, may not be the primary cause of fibrosis.”
The study, published in the journal Clinical Research Journal, Specifically, they studied a protein called lipopolysaccharide-binding protein (LBP), which is involved in the body’s immune response, and how LBP works in mice. The findings showed that mice without LBP in their liver cells had lower levels of liver inflammation and better liver function, but no changes in fibrosis.
In addition to mouse models, the researchers also studied genetic analyses of large human data sets and human tissue samples from MAFLD patients at different stages of the disease, to examine the consequences of loss of LBP function. The combined evidence showed that LBP does not alter scar tissue markers.
Sallam noted the need to further explore how LBP influences inflammation and whether other factors may offer a more potent reduction in inflammation and have an impact on reducing fibrosis.
“Reducing scar burden is one of the holy grails in treating advanced liver disease,” Sallam said. “These results suggest that certain ways of targeting inflammation may not be a viable option and that more targeted therapies against other pathways could help us better target fibrosis and improve outcomes for patients.”