Future Treatment Options in PBC

Because the etiopathogenesis of PBC is incompletely defined, curative therapies have not been identified, and the focus has been on prevention of disease progression. Ursodeoxycholic acid retards progression and is likely to be combined with newer therapies in future trials. Advances in our understanding of the roles of retroviral infection and autoimmune responses of T and B cells to PBC-specific autoantigens provides rationales for studies of the safety and efficacy of antiretroviral, immunosuppressive, and immunomodulatory agents in PBC. Promising options include inhibition of (1) T-cell activation and proliferation; (2) transendothelial migration and activation of effector cells; (4) cytokine and immunoglobulin effector mechanisms; and (5) inflammation and oxidation. Depletion and immunomodulation of T and B cells may provide opportunities to thwart re-emergence of effector mechanisms. Induction of tolerance in susceptible people before onset of disease or of hyporesponsiveness in established disease is increasingly feasible, as is prevention of biliary fibrosis.