Inflammatory pathways to liver fibrosis in non-alcoholic and alcoholic steatohepatitis: reversal by NLRP3 inhibitors

Nonalcoholic steatohepatitis (NASH) caused by obesity and diabetes made worse by alcohol, leads to cirrhosis. There is no effective treatment. In mice with NASH, MCC950, a novel drug that blocks NLRP3 (molecule that incites inflammation) reverses liver inflammation and possibly scarring. This proposal will test what activates NLRP3 in NASH, and whether blocking it completely with MCC950 or a new lasting longer inhibitor will dissolve severe liver scarring, and scarring made worse by alcohol.