*Article* **Real-World Clinical Management of Patients with Primary Biliary Cholangitis—A Retrospective Multicenter Study from Germany**

**Anne-Christin Beatrice Wilde 1,\*,†, Charlotte Lieb 1,†, Elise Leicht 1, Lena Maria Greverath 1, Lara Marleen Steinhagen 1, Nina Wald de Chamorro 1, Jörg Petersen 2, Wolf Peter Hofmann 3, Holger Hinrichsen 4, Renate Heyne 5, Thomas Berg 6, Uwe Naumann 7, Jeannette Schwenzer 8, Johannes Vermehren 9, Andreas Geier 10, Frank Tacke <sup>1</sup> and Tobias Müller <sup>1</sup>**


**Abstract:** Background: Clinical practice guidelines for patients with primary biliary cholangitis (PBC) have been recently revised and implemented for well-established response criteria to standard first-line ursodeoxycholic acid (UDCA) therapy at 12 months after treatment initiation for the early identification of high-risk patients with inadequate treatment responses who may require treatment modification. However, there are only very limited data concerning the real-world clinical management of patients with PBC in Germany. Objective: The aim of this retrospective multicenter study was to evaluate response rates to standard first-line UDCA therapy and subsequent Second-line treatment regimens in a large cohort of well-characterized patients with PBC from 10 independent hepatological referral centers in Germany prior to the introduction of obeticholic acid as a licensed second-line treatment option. Methods: Diagnostic confirmation of PBC, standard first-line UDCA treatment regimens and response rates at 12 months according to Paris-I, Paris-II, and Barcelona criteria, the follow-up cut-off alkaline phosphatase (ALP) ≤ 1.67 × upper limit of normal (ULN) and the normalization of bilirubin (bilirubin ≤ 1 × ULN) were retrospectively examined between June 1986 and March 2017. The management and hitherto applied second-line treatment regimens in patients with an inadequate response to UDCA and subsequent response rates at 12 months were also evaluated. Results: Overall, 480 PBC patients were included in this study. The median UDCA dosage was 13.2 mg UDCA/kg bodyweight (BW)/d. Adequate UDCA treatment response rates according to Paris-I, Paris-II, and Barcelona criteria were observed in 91, 71.3, and 61.3% of patients, respectively. In 83.8% of patients, ALP ≤ 1.67 × ULN were achieved. A total of 116 patients (24.2%) showed an inadequate response to UDCA according to at least one criterion. The diverse second-line treatment regimens applied led to significantly higher response rates according to Paris-II (35 vs. 60%, *p =* 0.005), Barcelona (13 vs. 34%, *p =* 0.0005), ALP ≤ 1.67 × ULN and bilirubin ≤ 1 × ULN (52.1 vs. 75%, *p* = 0.002). The addition of bezafibrates appeared to induce the

**Citation:** Wilde, A.-C.B.; Lieb, C.; Leicht, E.; Greverath, L.M.; Steinhagen, L.M.; Wald de Chamorro, N.; Petersen, J.; Hofmann, W.P.; Hinrichsen, H.; Heyne, R.; et al. Real-World Clinical Management of Patients with Primary Biliary Cholangitis—A Retrospective Multicenter Study from Germany. *J. Clin. Med.* **2021**, *10*, 1061. https:// doi.org/10.3390/jcm10051061

Academic Editor: Pierluigi Toniutto

Received: 14 February 2021 Accepted: 1 March 2021 Published: 4 March 2021

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strongest beneficial effect in this cohort (Paris II: 24 vs. 74%, *p* = 0.004; Barcelona: 50 vs. 84%, *p =* 0.046; ALP < 1.67 × ULN and bilirubin ≤ 1 × ULN: 33 vs. 86%, *p =* 0.001). Conclusion: Our large retrospective multicenter study confirms high response rates following UDCA first-line standard treatment in patients with PBC and highlights the need for close monitoring and early treatment modification in high-risk patients with an insufficient response to UDCA since early treatment modification significantly increases subsequent response rates of these patients.

**Keywords:** primary biliary cholangitis; autoantibodies; ursodeoxycholic acid; treatment response; second line therapy
