Upregulation of RIP3 is a common pathological feature in a range of human inflammation-driven liver diseases, namely hepatitis B and C, alcoholic liver disease, NASH, DILI and autoimmune hepatitis,9, 10, 11, 14 likely promoting inflammation in a necroptosis-dependent and -independent manner.30 Our results are the first to show that RIP3 and p-MLKL are simultaneously activated in liver parenchymal cells of PBC patients, suggesting that necroptosis likely has an active role in disease triggering and progression. Here, MLKL is linked to primary biliary cholangitis.