Serious side effects of long-term glucocorticoid treatment may outweigh the potential benefit. In this respect, the introduction of budesonide, a nonhalogenated corticosteroid with an extensive first-pass metabolism has been a promising innovation. A 2-year controlled double-blinded trial included 39 patients with early-stage PBC and compared treatment with UDCA plus budesonide against UDCA plus placebo. Combination therapy improved biochemical and histological features and reported only few corticosteroid-related side effects [284] . These promising results, however, could not be confirmed in a subsequent study from the Mayo Clinic. Here, adding budesonide for 1 year in 22 patients with suboptimal response to UDCA alone had only marginal effects on serum bilirubin and AP levels. In contrast, the Mayo risk score increased and there was a significant worsening of osteoporosis [285] . This open trial, however, included latestage patients, which may in part explain the disappointing results. As found in a short-term pharmacokinetic study, administration of budesonide to cirrhotic PBC patients leads to high plasma levels of budesonide associated with serious adverse effects and should therefore be avoided [286] . A Finish study [287] included only patients with stages I to III (n=77) in a 3-year randomized trial and used a lower dose of budesonide. The effects of budesonide plus UDCA were compared to UDCA alone. A significant improvement of histological features was observed in the combination group on top of the beneficial biochemical effects of UDCA alone. Long-term controlled trials are required to define whether combination of UDCA with budesonide provides a significant benefit in patients with early-stage PBC inadequately responding to UDCA monotherapy.