Severe alpha1-antitrypsin (AAT) deficiency (PiZZ genotype) causes liver disease due to accumulation of the mutant Z protein (Z-AAT), which presents histologically as Z-AAT globules. An open-label, Phase 2 study (NCT03946449) that was presented as a later breaker talk at EASL by Pavel Strnad, analyzed the efficacy of ARO-AAT, an RNAi therapeutic aiming to suppress Z-AAT synthesis. Serum Z-AAT was reduced after the first dose and sustained through 1 year (78-97% reductions). There was a substantial decrease in liver total Z-AAT protein at Week 24 (72-95%) and Week 48 (77-97%). All 9 patients had a decrease in the Z-AAT globules and sustained reductions in ALT and GGT. 6 of 9 patients had a ≥1-stage improvement in fibrosis at either Week 24 or 48. ARO-AAT was generally well tolerated. These data demonstrate that removal of the causative factor, Z-AAT, in AATD liver disease allows clearance of accumulated Z-AAT and can result in fibrosis regression.