UDCA is currently considered the mainstay of therapy for PBC [28, 29] . Randomized, double-blinded, placebocontrolled trials have consistently shown that UDCA, administered today in standardized doses of 13 to 15 mg/kg/day, improves serum biochemical markers including bilirubin [215] [216] [217] [218] 220] , an important prognostic marker in PBC [267] . A number of studies demonstrated an improvement of histological features by UDCA. In a combined analysis of four clinical trials including a total of 367 patients [268] and in an independent in 103 patients [221] , UDCA therapy was associated with delayed progression and a marked decrease in progression rate from early-stage disease to late histologic stages. Despite these effects on disease progression and severity, the assessment of the effect of UDCA treatment on long-term survival has been more difficult. A combined analysis of three randomized controlled trials including 548 patients in total treated with UDCA for up to 4 years revealed improved survival free of liver transplantation in patients with moderate or severe disease [222] . Another combined analysis of five studies, all with a follow-up of at least 4 years, quantified the reduction in the risk of death or liver transplantation in patients treated with UDCA to 32% [269] . A long-term follow-up study in a cohort of 225 patients, in part overlapping with the aforementioned analyses, reported 10-year survival without liver transplantation to be significantly higher in UDCA-treated patients compared with survival predicted by the Mayo model [270] . Recent long-term trials from France, Spain, and The Netherlands have shown comparable results [11] [12] [13] 271] . The survival rate of patients in early stages of the disease who biochemically responded to therapy was similar to that in the control populations. "Response" here is defined as a decrease in AP to <40% of pretreatment levels or normalization at 1 year (Barcelona criteria) [12] or serum bilirubin <1 mg/dl, AP≤3 × N and AST≤2 × N after 1 year of UDCA treatment (Paris criteria) [13, 14] . An additional nonrandomized controlled study from Greece confirmed that in most patients with PBC treated with UDCA (particularly those who are in early stage of disease), the 10-year survival is comparable to that in the general population [272] . Despite these intriguing findings, the beneficial effects of UDCA on survival have repeatedly been questioned: A large randomized Swedish trial failed to confirm an effect of UDCA on disease progression and survival at a dose of approximately 8 mg/kg/day [273] . It was concluded from this and other studies that doses of UDCA lower than 10 mg/kg/day are of little benefit. In the follow-up of patients in a US [274] and a Canadian trial [217] , UDCA had no significant influence on incidence of endpoints liver transplantation or death. Also, a meta-analysis of 11 randomized trials could not confirm a significant effect of UDCA on survival and incidence of liver transplantation [275] . In this meta-analysis, however, six studies with only 2 years of follow-up were included, as were two studies administering UDCA at low doses of 10 mg/kg/day or less. Other meta-analyses suffered from similar shortcomings [276, 277] and may therefore have missed a beneficial effect of UDCA. Accordingly, metaanalyses which only included long-term trials with followup of at least 2 years and those using an effective dose of UDCA of more than 10 mg/kg/day verified that treatment with UDCA significantly improves quality of life and transplant-free survival and delays histologic progression in early-stage patients [278, 279] . Current guidelines therefore recommend to treat PBC with UDCA using doses of 13 to 15 mg/kg/day and to start treatment early [28, 29, 280] .