Blocking EFHD1 reduces liver scarring by up to 60% in mice

A fatty, sugary diet left some mouse livers scarred and inflamed. But when University of Utah researchers blocked a protein called EFHD1, measures of liver inflammation and scarring fell by roughly 30% to 60% in mouse injury models and human liver organoids, lab-grown structures that mimic parts of the organ.

The finding addresses a gap in how obesity-related metabolic liver disease is understood. Excess fat affects hundreds of millions of people worldwide, yet only some fatty livers progress to injury, scarring and eventual failure. Earlier work had linked human genetic variants that increase EFHD1 to liver injury, but not to the buildup of liver fat itself.

The mechanism sits inside the cell. EFHD1 tethers mitochondria—the structures that support cellular energy production—to the endoplasmic reticulum, a nearby cell compartment, and helps mitochondria divide. When mice received a fatty, sugary diet, higher EFHD1 levels drove excessive division. The mitochondria then leaked double-stranded RNA into the cell, where it resembled material released during infection by viruses such as hepatitis C.

The liver responded as if it were under viral attack. That antiviral pathway, useful against an actual infection, instead shut down healthy but strained liver cells and worsened the injury. Removing EFHD1 produced long, string-like mitochondria rather than the compact, bean-shaped forms seen in ordinary liver cells, suggesting that less frequent division may prevent the RNA leak.

So what changes in practice? EFHD1 offers a possible second route for treatment alongside drugs that target lipid metabolism, which often only partly resolve liver injury. The University of Utah team is developing therapies to lower EFHD1, and mice lacking the protein showed normal activity, weight gain and other metabolic measures. The work is still preclinical: the reported benefits come from mice and human organoids, not from patients, and no human treatment or clinical result is reported.