**1. Introduction**

Primary biliary cholangitis (PBC) is a rare chronic inflammatory biliary disease characterized by the progressive destruction of intrahepatic bile ducts, leading to cholestasis and subsequent liver damage. Although immune-mediated processes are widely considered as a major underlying cause, the exact etiology of biliary inflammation still remains to be fully elucidated but likely comprises additional factors such as environmental stimuli and epigenetic factors [1]. If untreated, PBC may lead to end-stage liver cirrhosis and eventually liver failure. Orthotopic liver transplantation is the only definitive therapy for PBC patients with end-stage liver disease. Early treatment with weight-based ursodeoxycholic acid (UDCA) has been proven to extend transplant-free survival and is therefore recommended at a dosage of 13 to 15 mg UDCA/kg bodyweight (BW)/d as a standard first-line therapy by national and international PBC clinical practice guidelines [2–4]. These guidelines also implemented the evaluation of specific response criteria at 12 months after the initiation of UDCA treatment for the early detection of high-risk patients with inadequate treatment responses who need treatment modification. The most commonly applied Paris-I, Paris-II, and Barcelona criteria have been widely accepted for treatment monitoring including laboratory parameters such as bilirubin and alkaline phosphatase (ALP). Recently, ALP levels ≤ 1.67 × upper limit of normal (ULN)or ALP normalization and the normalization of bilirubin values (bilirubin ≤ 1 × ULN) have been proven to yield prognostic relevance [5,6]. The risk of PBC disease progression to severe liver disease in patients with PBC may also be estimated using the UK-PBC risk score, which is based on continuous variables that have been specifically developed to identify patients at an increased risk for progression to death or liver transplantation after 5, 10, and 15 years [7,8].

In December 2016, obeticholic acid was licensed as a second-line treatment option in combination with UDCA for patients with an inadequate UDCA response or monotherapy for patients with an intolerance to UDCA and is therefore recommended by current PBC clinical practice guidelines. Bezafibrates have also been shown to increase response rates in patients with an inadequate response to first-line UDCA therapy [9] and have therefore been depicted as a potential off-label second-line treatment option in combination with UDCA in the current guidelines.

There are only very limited data concerning the real-world clinical management of patients with PBC in Germany [10]. Moreover, a recent German population-based study reported the rising prevalence of PBC and deficits in their subsequent clinical management [11]. We therefore aimed to evaluate real-world diagnostic approaches, standard first-line UDCA treatment regimens and respective response rates at 12 months applying Paris-I, Paris-II, and Barcelona criteria, ALP levels ≤ 1.67 × ULN, and bilirubin ≤ 1 × ULN in a large cohort of well-characterized patients with PBC in a retrospective multicenter study from 10 independent hepatological referral centers in Germany. The real-world management of patients with an inadequate response to standard first-line UDCA treatment including the hitherto applied individual second-line treatment regimens prior to the introduction of obeticholic acid and the subsequent response rates at 12 months were also evaluated.
