Amongst several soluble checkpoint receptors and pro-inflammatory cytokines that were found to be elevated in patients with advanced/end-stage PBC (including soluble CD80, soluble LAG3, soluble CD137, IL-6, TNF-α, and CXCL10), our key findings highlight that IFN-γ levels increased as disease progressed and discriminated UDC responders and non-responders independently of cirrhosis, whereas elevated IFN-λ3 may have a role in advanced PBC that is distinct from IFN-λ2. Here, IFNL3 is linked to primary biliary cholangitis.