Can we cure primary biliary cholangitis?

Primary biliary cholangitis (PBC) is a chronic immune-mediated liver disease characterized by progressive destruction of the intrahepatic bile ducts, leading to cholestasis, fibrosis, and eventual cirrhosis. Despite advances in understanding disease pathogenesis, treatment pathways are focused on maintenance rather than cure. Moreover, the lion's share of therapeutic advances have been in the bile acid space, with currently available agents geared toward attenuating (rather than reversing) liver disease progression. In this review, we extend the therapeutic discussion beyond conventional treatments and explore paradigms rooted in autoimmune pathogenesis. In so doing, we highlight the potential role of regulatory T-cell modulation, nanoparticle-based antigen-specific tolerance, and epigenetic factors such as miRNA dysregulation, silencing bicarbonate transporters. We go on to discuss relevant concepts from autoimmune diseases more broadly, including altered peptide ligands for T-cell deviation, decoy molecules, and antigen-specific T-cell suicide pathways, contextualized with PBC-relevant data. In so doing, we posit that PBC may, in the future, be defined as a curable disease.