Hepatobiliary long-term consequences of COVID-19: dramatically increased rate of secondary sclerosing cholangitis in critically ill COVID-19 patients

Silke Leonhardt*, Christian Jürgensen, Josephine Frohme, Donata Grajecki, Andreas Adler, Michael Sigal, Julia Leonhardt, Julian M. Voll, Jan Matthias Kruse, Roland Körner, Kai Uwe Eckardt, Hans Joachim Janssen, Volker Gebhardt, Marc D. Schmittner, Stefan Hippenstiel, Martin Witzenrath, Norbert Suttorp, Elisa T. Helbig, Lena J. Lippert, Paula StubbemannPinkus Tober-Lau, David Hillus, Sascha S. Haenel, Alexandra Horn, Willi M. Koch, Nadine Olk, Mirja Mittermaier, Fridolin Steinbeis, Tilman Lingscheid, Bettina Temmesfeld-Wollbrück, Thomas Zoller, Holger Müller-Redetzky, Alexander Uhrig, Daniel Grund, Christoph Ruwwe-Glösenkamp, Miriam S. Stegemann, Katrin M. Heim, Ralf H. Hübner, Christian Drosten, Victor M. Corman, Bastian Opitz, Martin Möckel, Felix Balzer, Claudia Spies, Steffen Weber-Carstens, Chantip Dang-Heine, Michael Hummel, Georg Schwanitz, Uwe D. Behrens, Christof von Kalle, Pa-COVID-19 collaborative study group

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

Abstract

Background: Increasing evidence suggests that secondary sclerosing cholangitis (SSC), which can lead to cirrhosis or liver failure, may be a hepatobiliary long-term complication of COVID-19. The aim of this study was to estimate the frequency and outcome of this COVID-19 sequela and to identify possible risk factors. Methods: This observational study, conducted at University Hospital Charité Berlin and Unfallkrankenhaus Berlin, Germany, involved hospitalized patients with COVID-19 pneumonia, including 1082 ventilated COVID-19 patients. We compared COVID-19 patients who developed SSC with a COVID-19 control group by univariate and multivariate analyses. Results: SSC occurrence after COVID-19 was observed exclusively in critically ill patients with invasive ventilation, albeit with extreme clustering among them. One in every 43 invasively ventilated COVID-19 patients developed this complication. Risk factors preceding the development of secondary sclerosing cholangitis in critically ill COVID-19 patients (SSC-CIP) were signs of systemic reduced blood oxygen supply (e.g., low PaO2/FiO2, ischemic organ infarctions), multi-organ failure (high SOFA score) at admission, high fibrinogen levels and intravenous ketamine use. Multivariate analysis confirmed fibrinogen and increased plasma lactate dehydrogenase as independent risk factors associated with cholangiopathy onset. The 1-year transplant-free survival rate of COVID-19-associated SSC-CIP was 40%. Conclusions: COVID-19 causes SSC-CIP in a substantial proportion of critically ill patients. SSC-CIP most likely develops due to severe tissue hypoxia and fibrinogen-associated circulatory disturbances. A significant increase of patients with SSC-CIP is to be expected in the post-COVID era.

Original languageEnglish
Pages (from-to)1610-1625
Number of pages16
JournalHepatology International
Volume17
Issue number6
DOIs
Publication statusPublished - Dec 2023

Keywords

  • COVID-19 associated SSC-CIP
  • COVID-19 cholangiopathy
  • COVID-19 long-term consequences
  • Ischemic cholangiopathy
  • Secondary sclerosing cholangitis in critically ill patients

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