Corticosteroids and other immunosuppressive agents have been evaluated for therapeutic use in PBC. In a 3-year, placebo-controlled trial including 36 patients with PBC, prednisolone significantly improved serum AP levels, IgGs, and AMA and diminished deterioration of liver histology, whereas bone loss was aggravated [281] . Combination of UDCA and prednisolone in comparison to UDCA alone resulted in a significant improvement of histological features [282] . It is yet unclear whether increased expression of AE2 isoforms contributes to the beneficial effect of combined treatment with UDCA and corticosteroids in PBC. Experimentally, enhanced expression of alternative AE2 isoforms and enhanced transport capacity for bicarbonate in human cholangiocytes and in a hepatocyte cell line were demonstrated [283] . AE2 expression and biliary bicarbonate secretion is usually diminished in PBC [241] .