Search

Real-world data on the management of patients with primary biliary cholangitis (PBC) are so far scarce in Germany. Therefore, we aimed to establish a nationwide registry and describe the clinical characteristics and therapy of PBC patients.Three different cohorts defined as ursodeoxycholic acid (UDCA) responders, as inadequate responders according to Paris II criteria, and as newly diagnosed patients were prospectively recruited.This manuscript includes the baseline data of the project.In total, 33/77 (43%) contacted centres (58% of university hospitals, 38% of non-university hospitals, and 24% of private practices) recruited 515 patients including 204 UDCA responders, 221 inadequate responders to UDCA, and 90 newly diagnosed patients.All patients were treated with UDCA; however, a UDCA dosage below the recommended dosage of 13 mg/kg/d was observed in 38.5% of individuals after 12 months of treatment. UDCA dosages were lower in nonacademic compared to academic centres.Only 75/219 (38.5%) of inadequate responders to UDCA received a second-line therapy with obeticholic acid (OCA) and/or bezafibrate (BZF). OCA (13% vs. 4.5%) and BZF (14% vs. 6.5%) were significantly more often prescribed by academic vs. nonacademic centres.Pruritus (27% vs. 15.5%), fatigue (23% vs. 4.5%), and sicca syndrome (14% vs. 1%) were significantly more often reported by academic centres.The German PBC registry could be established, which indicates suboptimal therapy in a relevant proportion of patients and shows significant differences between academic and nonacademic centres. Results are fundamental to improving clinical management at different levels of care., Competing Interests: JW: Lecturer and advisory board member for Intercept/Advanz Pharma, GSK, Ipsen TM: Ssupported by the German Research Foundation Grants MU 2864/1-3 and MU 2864/3- 1.KS: Receipt of speaker´s honoraria or advisory board: Gilead, Intercept/Advanz Pharma, Abbvie, Falk, Novo Nordisk HB: Consultant: Intercept/Advance Pharma, Ipsen GD: Consultant / speaker: AbbVie, Advanz/Intercept, Alexion, Falk Foundation, Gilead, Novartis, Orphalan, Univar PAR: Consulting and lectures fees: Astra Zeneca, BMS, Boston Scientific, CSL Behring, Gilead, Pfizer, Abbvie, Norgine JMS: Consultant: Astra Zeneca, Apollo Endosurgery, Bayer, Boehringer Ingelheim, BMS, Gilead Sciences, GSK, Intercept Pharmaceuticals, Ipsen, Inventiva Pharma, Madrigal, MSD, Northsea Therapeutics, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, Siemens Healthineers. Research Funding: Gilead Sciences, Boehringer Ingelheim, Siemens Healthcare GmbH. Stock Options: AGED diagnostics, Hepta Bio. Speaker Honorarium: Boehringer Ingelheim, Echosens, MedPublico GmbH, Novo Nordisk, Madrigal Pharmaceuticals, Histoindex, MedPublico GmbH SZ: Speakers bureau and/or consultancy: Abbvie, BioMarin, Boehringer Ingelheim, Gilead, GSK, Intercept, Ipsen, Janssen, Madrigal, MSD/Merck, NovoNordisk, SoBi, Theratechnologies KGS: Consultant: Advance Pharma, Speaker Honorarium: AbbVie, GileadJT has received speaking and/or consulting fees from Versantis, Gore, Boehringer-Ingelheim, Falk, Grifols, Genfit and CSL Behring. WPH: Consultant or Speaker Honorarium: Intercept /Advanz, Ipsen, NovoNordisk, Gilead, Abbvie, Norgine CS: Consultant, Study support or Speaker Honorarium: Calliditas, Falk, Intercept/Advanz, Ipsen, Mirum ER: Receipt of honoraria or consultation fees/advisory board: Abbvie, Amgen, Intercept, Medac, Merz, Norgine, Falk Foundation, Gilead, Pfizer, Repha, Takeda AEK: Research grant: Intercept. Speakers bureau: Abbvie, Advanz, AOP Orphan, Bayer, BMS, CMS, CymaBay, Falk, Gilead, GSK, Intercept, Ipsen, Newbridge, Novartis, Lilly, Mirum, MSD, Roche, Zambon. Consultant: Abbvie, Advanz, Alentis, AlphaSigma, AstraZenca, Avior, Bayer, BioNTech, CymaBay, Eisai, Escient, Falk, FMC, Gilead, GSK, Guidepoint, Intercept, Ipsen, Mirum, Medscape, MSD, Myr, Roche, Takeda, Viofor MR: Consultant, or Speaker Honorarium: Intercept/Advanz, Gilead, Abbvie AT: Speaker Honorarium: Intercept/Advanz VK: Consultant Astra Zeneca, Speaker’s Honoraria from AbbVie, Gilead, Falk, Mirum, Albireo/Ipsen, Merck, MedUpdate GmbH, Sanofi, CSL Behring ER: Receipt of honoraria or consultation fees/advisory board: Abbvie, Amgen, Intercept, Medac, Merz, Norgine, Falk Foundation, Gilead, Pfizer, Repha, Takeda FT: Research grant: Allergan, BMS, Inventiva, Gilead. Speakers bureau: Gilead, Abbvie, Falk, Merz, Orphalan, Advanz. Consultant: Allergan, AstraZeneca, Gilead, Abbvie, Alnylam, BMS, Intercept / Advanz, Inventiva, Pfizer, Novartis, Novo Nordisk, Sanofi. CT: Receipt of honoraria or consultation fees/advisory board: Intercept/Advanz Pharma TB: Receipt of grants/research supports: Abbvie, BMS, Gilead, MSD/Merck, Humedics, Intercept, Merz, Norgine, Novartis, Orphalan, Sequana Medical; Receipt of honoraria or consultation fees/advisory board: Abbvie, Alexion, Albireo, Bayer, Gilead, GSK, Eisai, Enyo Pharma, HepaRegeniX GmbH, Humedics, Intercept, Ipsen, Janssen, MSD/Merck, Novartis, Orphalan, Roche, Sequana Medical, SIRTEX, SOBI, and Shionogi; Participation in a company sponsored speaker’s bureau: Abbvie, Advance Pharma, Alexion, Albireo, Bayer, Gilead, Eisai, Falk Foundation, Intercept, Ipsen, Janssen, MedUpdate GmbH, MSD/Merck, Novartis, Orphalan, Sequana Medica, SIRTEX, and SOBI Nothing to disclose: AF, RG, UN, TB, AW, MH, RG, CB, TTW, RB, HG, ND, MM, PM, JUM, AK, KP, NKB, (Thieme. All rights reserved.)

Competing Interests: Die Interessenerklärungen aller Expert*innen sind im Anhang aufgeführt.

Background and Aims: Non-alcoholic steatohepatitis (NASH) is a chronic disease that can progress to end-stage liver disease (ESLD). A large proportion of early-stage NASH patients remain undiagnosed compared to those with advanced fibrosis, who are more likely to receive disease management interventions. This study estimated the disease burden and economic impact of diagnosed NASH in the adult population of France, Germany, Italy, Spain and the United Kingdom in 2018., Methods: The socioeconomic burden of diagnosed NASH was estimated using cost-of-illness methodology applying a prevalence approach to estimate the number of adults with NASH and the attributable economic and wellbeing costs. Given undiagnosed patients do not incur costs in the study, the probability of diagnosis is central to cost estimation. The analysis was based on a literature review, databases and consultation with clinical experts, economists and patient groups., Results: The proportion of adult NASH patients with a diagnosis ranged from 11.9% to 12.7% across countries, which increased to 38.8%-39.1% for advanced fibrosis (F3-F4 compensated cirrhosis). Total economic costs were €8548-19 546M. Of these, health system costs were €619-1292M. Total wellbeing costs were €41 536-90 379M. The majority of the undiagnosed population (87.3%-88.2% of total prevalence) was found to have early-stage NASH, which, left untreated, may progress to more resource consuming ESLD over time., Conclusions: This study found that the majority of economic and wellbeing costs of NASH are experienced in late disease stages. Earlier diagnosis and care of NASH patients could reduce future healthcare costs., (© 2021 The Authors. Liver International published by John Wiley & Sons Ltd.)

Objective: Homozygous alpha1-antitrypsin (AAT) deficiency increases the risk for developing cirrhosis, whereas the relevance of heterozygous carriage remains unclear. Hence, we evaluated the impact of the two most relevant AAT variants ('Pi*Z' and 'Pi*S'), present in up to 10% of Caucasians, on subjects with non-alcoholic fatty liver disease (NAFLD) or alcohol misuse., Design: We analysed multicentric case-control cohorts consisting of 1184 people with biopsy-proven NAFLD and of 2462 people with chronic alcohol misuse, both cohorts comprising cases with cirrhosis and controls without cirrhosis. Genotyping for the Pi*Z and Pi*S variants was performed., Results: The Pi*Z variant presented in 13.8% of patients with cirrhotic NAFLD but only in 2.4% of counterparts without liver fibrosis (p<0.0001). Accordingly, the Pi*Z variant increased the risk of NAFLD subjects to develop cirrhosis (adjusted OR=7.3 (95% CI 2.2 to 24.8)). Likewise, the Pi*Z variant presented in 6.2% of alcohol misusers with cirrhosis but only in 2.2% of alcohol misusers without significant liver injury (p<0.0001). Correspondingly, alcohol misusers carrying the Pi*Z variant were prone to develop cirrhosis (adjusted OR=5.8 (95% CI 2.9 to 11.7)). In contrast, the Pi*S variant was not associated with NAFLD-related cirrhosis and only borderline with alcohol-related cirrhosis (adjusted OR=1.47 (95% CI 0.99 to 2.19))., Conclusion: The Pi*Z variant is the hitherto strongest single nucleotide polymorphism-based risk factor for cirrhosis in NAFLD and alcohol misuse, whereas the Pi*S variant confers only a weak risk in alcohol misusers. As 2%-4% of Caucasians are Pi*Z carriers, this finding should be considered in genetic counselling of affected individuals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)