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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 x 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 x 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 x ULN and bilirubin ≤ 1 x ULN (52.1 vs. 75%, p = 0.002). The addition of bezafibrates appeared to induce the strongest beneficial effect in this cohort (Paris II: 24 vs. 74%, p = 0.004; Barcelona: 50 vs. 84%, p = 0.046; ALP < 1.67x 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.

We present four patients who underwent simultaneous liver-kidney transplantation (SLK) and were diagnosed with calciphylaxis, also known as calcific uremic arteriolopathy (CUA). Common characteristics included high MELD scores (mean 35.2 AE 4.8) and advanced renal disease (duration range 6-44 weeks). CUA was diagnosed within the first 2 months post-SLK based on clinical features. Severe morbidity and prolonged hospital stay were observed and one of the patients died secondary to sepsis. Treatment included metabolic support, wound care, calcium level correction and use of sodium thiosulphate. CUA should be considered in the presence of painful dermatologic changes in patients status post SLK.

Aim Muscarinic acetylcholine receptor type 3‐mediated signaling might be involved in the pathogenesis of chronic inflammatory biliary diseases, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). The aim of the present study was to investigate the prevalence of five well‐characterized specific single‐nucleotide polymorphisms within the muscarinic acetylcholine receptor type 3 gene, CHRM3 (rs11578320, rs6690809, rs6429157, rs7548522, and rs4620530), in patients with PBC and PSC. Patients with chronic hepatitis C (CHC) and healthy individuals served as control cohorts. In the PBC cohort, baseline characteristics and response to ursodeoxycholic acid therapy applying established response criteria at 12 months after the initiation of treatment were evaluated according to the underlying CHRM3 genotype. Methods CHRM3 genotyping was carried out in 306 PBC patients, 205 PSC patients, 208 CHC patients, and 240 healthy controls from two independent German tertiary care university centers in Berlin and Leipzig, Germany. Results CHRM3 rs4620530 proportions in patients with PBC significantly differed from patients with PSC (P = 0.005), CHC (P = 0.009), and healthy controls (P = 0.008), primarily due to a substantial overrepresentation of the T allele in PBC (49.3% in PBC vs. 39.8% in PSC, 35.7% in CHC, and 40% in healthy controls), indicating a potential association of the rs4620530 T allele with PBC (OR 1.461, 95% CI 1.147–1.861, P = 0.002). Further analysis showed no association of CHRM3 single‐nucleotide polymorphism rs4620530 with baseline characteristics and ursodeoxycholic acid treatment response in PBC. Conclusion CHRM3 single‐nucleotide polymorphism rs4620530 might confer an increased genetic risk for the development of PBC.

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