That antiviral stress response, meant to prevent viral replication in infected cells, instead shuts down healthy but strained liver cells, worsening injury. When the researchers blocked or reduced the levels of EFHD1, measures of inflammation and liver scarring dropped by roughly 30 to 60%, in both diet-induced and drug-induced mouse liver injury models, as well as in human liver organoids.
Current drugs for obesity-related metabolic liver disease primarily target lipid metabolism and frequently only partially resolve liver injury. The researchers view EFHD1 as a complementary target for new therapies. “We think this is a unique opportunity because even if these other drugs work, the effects are often partial,” Chaudhuri said.
The research team is currently working to develop therapies to decrease EFHD1 levels, building on work covered by a patent filed by the university.
Reassuringly, mice engineered to lack EFHD1 have normal activity levels, weight gain, and other measures of metabolism, which suggests that treatments that block EFHD1 would have few side effects.
Future studies will explore whether the same pathway drives injury in metabolic diseases of the heart and other organs, and whether it also contributes to alcohol-related liver damage.