Critical parameters under the expanded “two hit hypothesis” were examined as potential underlying mechanism(s) to explain the differential effects between WT and Cyp2e1-null mice fed FF, i.e., by examining hepatic steatosis “the first hit” and various “second hit” factors such as oxidative stress, inflammatory response, gut-derived serum endotoxin, ER stress, and IR, which can contribute to liver fibrosis5, 6, 7. The gene discussed is CYP2E1; the disease is fatty liver disease.