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For: The Keta-Cov research groupMalletVincent1BockKilian23MandenguePaul Doumbe1DufourNicolas4VoigtlaenderTorsten2RicardJean-Damien5IsnardPierre6FrochotVincent78LetavernierEmmanuel78MogaLucile9LandrieuxAmandine9RautouPierre-Emmanuel9Pons-KerjeanNathalie10Vallet-PichardAnaïs1ChouchanaLaurent11GernezCoralie5BurgerCarole12ScemlaAnne12de TymoskiChristian131415DepretFrançois131415DudoignonEmmanuel131415LamhautLionel16FlicoteauRémi17RousseauGéraldine18Duong Van HuyenJean-Paul6CorreasJean-Michel19WedemeyerHeiner23PolStanislas11Université de Paris, AP-HP, Hôpital Cochin, DMU Cancérologie et spécialités médico-chirurgicales, Service d’Hépatologie, Paris, France2Dept. of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany3German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, France4Centre Hospitalier René Dubos, 95300 Pontoise, France5Université de Paris, AP-HP, Hôpital Louis Mourier, DMU Esprit, Service de Réanimation Médico-Chirurgicale, Colombes, France6Université de Paris, AP-HP, Hôpital Necker Enfants Malades, DMU Imagina, Service d’Anatomo-Pathologie, Paris, France7Sorbonne Université, AP-HP, Hôpital Tenon, DMU Biogem, Service de Physiologie, F-75020 Paris, France8INSERM, UMR S 1155, Hôpital Tenon, F-75020 Paris, France9Université de Paris, AP-HP, Hôpital Beaujon, Service d'Hépatologie, DMU Digest, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Centre de recherche sur l'inflammation, Inserm, UMR 1149, Paris, France10AP-HP, Hôpital Beaujon, Service de Pharmacie, DMU Prisme, Paris, France11Université de Paris, AP-HP, Hôpital Cochin, DMU Prime, Service de Pharmacovigilance, Paris, France12Université de Paris, AP-HP, Hôpital Necker Enfants Malades, DMU Carte, Service de Néphrologie et de Transplantation rénale, Paris, France13Université de Paris, AP-HP, Groupe Hospitalier St-Louis-Lariboisière, DMU Parabol, Département d’Anesthésie Réanimation et Centre de Traitement des Brûlés, Paris, France14FHU Promice, Paris, France15INI-CRCT, Nancy, France16Université de Paris, AP-HP, Hôpital Necker Enfants Malades, Department of Anesthesiology and Critical Care, Paris, France17Université de Paris, AP-HP, Hôpital Saint Louis, DMU Prisme, Service de Biostatistique et Information Médicale, Paris, France18Service de Chirurgie Digestive, Hépato-Bilio-Pancréatique et Transplantation Hépatique, Hôpital Pitié-Salpêtrière, DMU SAPERE - APHP Sorbonne Université, France19Université de Paris, AP-HP, Hôpital Necker Enfants Malades, DMU Imagina, Service de Radiologie, Paris, France. Intravenous ketamine and progressive cholangiopathy in COVID-19 patients. J Hepatol 2021;74:1243-1244. [PMID: 33617925 PMCID: PMC7893247 DOI: 10.1016/j.jhep.2021.02.007] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 02/03/2021] [Accepted: 02/08/2021] [Indexed: 02/07/2023]

For:	The Keta-Cov research groupMalletVincent1BockKilian23MandenguePaul Doumbe1DufourNicolas4VoigtlaenderTorsten2RicardJean-Damien5IsnardPierre6FrochotVincent78LetavernierEmmanuel78MogaLucile9LandrieuxAmandine9RautouPierre-Emmanuel9Pons-KerjeanNathalie10Vallet-PichardAnaïs1ChouchanaLaurent11GernezCoralie5BurgerCarole12ScemlaAnne12de TymoskiChristian131415DepretFrançois131415DudoignonEmmanuel131415LamhautLionel16FlicoteauRémi17RousseauGéraldine18Duong Van HuyenJean-Paul6CorreasJean-Michel19WedemeyerHeiner23PolStanislas11Université de Paris, AP-HP, Hôpital Cochin, DMU Cancérologie et spécialités médico-chirurgicales, Service d’Hépatologie, Paris, France2Dept. of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany3German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, France4Centre Hospitalier René Dubos, 95300 Pontoise, France5Université de Paris, AP-HP, Hôpital Louis Mourier, DMU Esprit, Service de Réanimation Médico-Chirurgicale, Colombes, France6Université de Paris, AP-HP, Hôpital Necker Enfants Malades, DMU Imagina, Service d’Anatomo-Pathologie, Paris, France7Sorbonne Université, AP-HP, Hôpital Tenon, DMU Biogem, Service de Physiologie, F-75020 Paris, France8INSERM, UMR S 1155, Hôpital Tenon, F-75020 Paris, France9Université de Paris, AP-HP, Hôpital Beaujon, Service d'Hépatologie, DMU Digest, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Centre de recherche sur l'inflammation, Inserm, UMR 1149, Paris, France10AP-HP, Hôpital Beaujon, Service de Pharmacie, DMU Prisme, Paris, France11Université de Paris, AP-HP, Hôpital Cochin, DMU Prime, Service de Pharmacovigilance, Paris, France12Université de Paris, AP-HP, Hôpital Necker Enfants Malades, DMU Carte, Service de Néphrologie et de Transplantation rénale, Paris, France13Université de Paris, AP-HP, Groupe Hospitalier St-Louis-Lariboisière, DMU Parabol, Département d’Anesthésie Réanimation et Centre de Traitement des Brûlés, Paris, France14FHU Promice, Paris, France15INI-CRCT, Nancy, France16Université de Paris, AP-HP, Hôpital Necker Enfants Malades, Department of Anesthesiology and Critical Care, Paris, France17Université de Paris, AP-HP, Hôpital Saint Louis, DMU Prisme, Service de Biostatistique et Information Médicale, Paris, France18Service de Chirurgie Digestive, Hépato-Bilio-Pancréatique et Transplantation Hépatique, Hôpital Pitié-Salpêtrière, DMU SAPERE - APHP Sorbonne Université, France19Université de Paris, AP-HP, Hôpital Necker Enfants Malades, DMU Imagina, Service de Radiologie, Paris, France. Intravenous ketamine and progressive cholangiopathy in COVID-19 patients. J Hepatol 2021;74:1243-1244. [PMID: 33617925 PMCID: PMC7893247 DOI: 10.1016/j.jhep.2021.02.007] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 02/03/2021] [Accepted: 02/08/2021] [Indexed: 02/07/2023]

Number

Cited by Other Article(s)

Borges VFA, Cotrim HP, Andrade ARCF, Mendes LSC, Penna FGC, Silva MC, Salomão FC, Freitas LAR. COVID-19-Related Cholangiopathy: Histological Findings. Diagnostics (Basel) 2024;14:1804. [PMID: 39202292 PMCID: PMC11354040 DOI: 10.3390/diagnostics14161804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 08/06/2024] [Accepted: 08/14/2024] [Indexed: 09/03/2024] Open

Leonhardt S, Grajecki D, Geisel D, Fehrenbach U, Adler A, Leonhardt J, Horst D, Kurth F, Thibeault C, Janssen HJ, Kaul T, Faiss S, Tacke F, Jürgensen C. Endoscopic Features of Post-COVID-19 Cholangiopathy and Its Management Using ERCP. Am J Gastroenterol 2024;119:748-759. [PMID: 37843039 PMCID: PMC10984637 DOI: 10.14309/ajg.0000000000002562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Accepted: 09/22/2023] [Indexed: 10/17/2023]

Abstract

INTRODUCTION

Despite growing awareness of post-coronavirus disease 2019 (COVID-19) cholangiopathy as one of the most serious long-term gastrointestinal consequences of COVID-19, the endoscopic features of this disease are still poorly characterized. This study aimed to more precisely define its endoscopic features and to outline the role of endoscopic retrograde cholangiopancreatography (ERCP) in the management of this entity.

METHODS

In this observational study, 46 patients with confirmed post-COVID-19 cholangiopathy were included.

RESULTS

Based on the endoscopic features observed in 141 ERCP procedures, post-COVID-19 cholangiopathy can be classified as a variant of secondary sclerosing cholangitis in critically ill patients. It appeared early in the course of intensive care treatment of patients with COVID-19 (cholestasis onset 4.5 days after intubation, median). This form of cholangiopathy was more destructive than stricturing in nature and caused irreversible damage to the bile ducts. A centripetal pattern of intrahepatic bile duct destruction, the phenomenon of vanishing bile ducts, the absence of extrahepatic involvement, and the presence of intraductal biliary casts (85% of patients) were typical cholangiographic features of post-COVID-19 cholangiopathy. This cholangiopathy was often complicated by small peribiliary liver abscesses with isolation of Enterococcus faecium and Candida spp. in bile culture. The prognosis was dismal, with a 1-year liver transplantation-free survival rate of 44%. In particular, patients with peribiliary liver abscesses or destruction of the central bile ducts tended to have a poor prognosis (n.s.). As shown by multivariate analysis, bilirubin levels (on intensive care unit day 25-36) negatively correlated with liver transplantation-free survival (hazard ratio 1.08, P < 0.001). Interventional endoscopy with cast removal had a positive effect on cholestasis parameters (gamma-glutamyl transpeptidase, alkaline phosphatase, and bilirubin); approximately 60% of all individual values decreased.

DISCUSSION

Gastrointestinal endoscopy makes an important contribution to the management of post-COVID-19 cholangiopathy. ERCP is not only of great diagnostic and prognostic value but also has therapeutic value and therefore remains indispensable.

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Affiliation(s)

Silke Leonhardt Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
Donata Grajecki Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
Dominik Geisel Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
Uli Fehrenbach Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
Andreas Adler Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
Julia Leonhardt Department of Anesthesiology and Intensive Care Medicine, University Hospital Jena and Center for Sepsis Control and Care, University Hospital Jena, Jena, Germany
David Horst Institute of Pathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
Florian Kurth Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
Charlotte Thibeault Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
Hans-Joachim Janssen Department of Anesthesiology, Intensive Care and Pain Medicine, BG Klinikum Unfallkrankenhaus Berlin gGmbH, Berlin, Germany
Thomas Kaul Department of Internal Medicine, BG Klinikum Unfallkrankenhaus Berlin gGmbH, Berlin, Germany
Siegbert Faiss Department of Internal Medicine, BG Klinikum Unfallkrankenhaus Berlin gGmbH, Berlin, Germany
Frank Tacke Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
Christian Jürgensen Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

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Yoo N, Thomas S, Bender M, Cheng XJC. A Case of Hepatotoxicity Induced by Therapeutic Ketamine Use for Sedation. Case Rep Crit Care 2024;2024:8366034. [PMID: 38505599 PMCID: PMC10950395 DOI: 10.1155/2024/8366034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 01/23/2024] [Accepted: 02/19/2024] [Indexed: 03/21/2024] Open

De Tymowski C, Dépret F, Dudoignon E, Moreno N, Zagdanski AM, Hodjat K, Deniau B, Mebazaa A, Legrand M, Mallet V, for the Keta-Cov research group. Ketamine restriction correlates with reduced cholestatic liver injury and improved outcomes in critically ill patients with burn injury. JHEP Rep 2024;6:100950. [PMID: 38304235 PMCID: PMC10832380 DOI: 10.1016/j.jhepr.2023.100950] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Accepted: 09/29/2023] [Indexed: 02/03/2024] Open

Abstract

Background & Aims

Ketamine-associated cholestatic liver injury is reported in patients with severe burn injury, but its association with patient outcome is unclear. We investigated the relationship between ketamine exposure, cholestatic liver injury, and outcome of critically ill patients with burn injury.

Methods

In a retrospective study, patients with severe burn injury were analysed across two periods: unrestricted ketamine prescription (ketamine-liberal) and capped ketamine dosage (ketamine-restricted). The primary endpoint was cholestatic liver injury, and the secondary endpoint was 3-month mortality. Binary logistic regression models and the revised electronic causality assessment method were used to measure the strength of associations and causality assessment, respectively.

Results

Of 279 patients (median age 51 [IQR 31-67] years; 63.1% men; burned surface area 28.5%, IQR 20-45%), 155 (56%) were in the ketamine-liberal group, and 124 (44%) were in the ketamine-restricted group, with comparable clinical characteristics, except for ketamine exposure (median doses 265.0 [IQR 0-8,021] mg and 20 [IQR 0-105] mg, respectively; p <0.001). A dose- and time-dependent relationship was observed between ketamine exposure and cholestatic liver injury. Ketamine restriction was associated with a reduced risk of cholestatic liver injury (adjusted odds ratio 0.16, 95% CI 0.04-0.50; p = 0.003) and with a higher probability of 3-month survival (p = 0.035). The revised electronic causality assessment method indicated that ketamine was probably and possibly the cause of cholestatic liver injury for 14 and 10 patients, respectively. Cholangitis was not observed in the ketamine-restricted group. In propensity-matched patients, the risk of 3-month mortality was higher (adjusted odds ratio 9.92, 95% CI 2.76-39.05; p = 0.001) in patients with cholestatic liver injury and ketamine exposure ≥10,000 mg. Other sedative drugs were not associated with liver and patient outcome.

Conclusions

In this cohort, ketamine restriction was associated with less cholestatic liver injury and reduced 3-month mortality.

Impact and implications

In a cohort of 279 critically ill patients with burn injury, ketamine was associated with a risk of liver bile duct toxicity. The risk was found to be dependent on both the dosage and duration of ketamine use. A restriction policy of ketamine prescription was associated with a risk reduction of liver injury and 3-month mortality. These findings have implications for the analgesia and sedation of critically ill patients with ketamine, with higher doses raising safety concerns.

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Affiliation(s)

Christian De Tymowski Université Paris Cité, Paris, France Department of Anaesthesiology and Surgical Intensive Care Unit, Groupe Hospitalier Bichat Claude Bernard, DMU PARABOL, Assistance Publique–Hôpitaux de Paris, Paris, France Department of Anaesthesiology, Hôpital Louis Mourier, DMU PARABOL, Assistance Publique–Hôpitaux de Paris, Paris, France AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, DMU PARABOL, Département d’anesthésie réanimation et centre de traitement des brûlés, Paris, France Université Paris Cité, Centre de Recherche sur l’Inflammation, INSERM UMR 1149, CNRS ERL8252, Paris, France
François Dépret Université Paris Cité, Paris, France AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, DMU PARABOL, Département d’anesthésie réanimation et centre de traitement des brûlés, Paris, France Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM UMR-S 942 Mascot, Lariboisière Hospital, Paris, France INI-CRCT Network, Nancy, France FHU PROMICE, Paris, France
Emmanuel Dudoignon Université Paris Cité, Paris, France AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, DMU PARABOL, Département d’anesthésie réanimation et centre de traitement des brûlés, Paris, France FHU PROMICE, Paris, France
Nabila Moreno AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, Laboratoire de Biochimie, Paris, France
Anne-Marie Zagdanski AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, Département de radiologie, Paris, France
Kyann Hodjat AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, DMU PARABOL, Département d’anesthésie réanimation et centre de traitement des brûlés, Paris, France
Benjamin Deniau Université Paris Cité, Paris, France AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, DMU PARABOL, Département d’anesthésie réanimation et centre de traitement des brûlés, Paris, France Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM UMR-S 942 Mascot, Lariboisière Hospital, Paris, France FHU PROMICE, Paris, France
Alexandre Mebazaa Université Paris Cité, Paris, France AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, DMU PARABOL, Département d’anesthésie réanimation et centre de traitement des brûlés, Paris, France Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM UMR-S 942 Mascot, Lariboisière Hospital, Paris, France FHU PROMICE, Paris, France
Matthieu Legrand INI-CRCT Network, Nancy, France Department of Anesthesia and Peri-operative Care, Division of Critical Care Medicine, University of California, San Francisco, CA, USA
Vincent Mallet Université Paris Cité, Paris, France AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, DMU PARABOL, Département d’anesthésie réanimation et centre de traitement des brûlés, Paris, France Assistance Publique–Hôpitaux de Paris (AP-HP), Groupe Hospitalier Cochin Port Royal, DMU Cancérologie et spécialités médico-chirurgicales, Service de Maladie du Foie, Paris, France
for the Keta-Cov research group Université Paris Cité, Paris, France Department of Anaesthesiology and Surgical Intensive Care Unit, Groupe Hospitalier Bichat Claude Bernard, DMU PARABOL, Assistance Publique–Hôpitaux de Paris, Paris, France Department of Anaesthesiology, Hôpital Louis Mourier, DMU PARABOL, Assistance Publique–Hôpitaux de Paris, Paris, France AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, DMU PARABOL, Département d’anesthésie réanimation et centre de traitement des brûlés, Paris, France Université Paris Cité, Centre de Recherche sur l’Inflammation, INSERM UMR 1149, CNRS ERL8252, Paris, France Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM UMR-S 942 Mascot, Lariboisière Hospital, Paris, France INI-CRCT Network, Nancy, France FHU PROMICE, Paris, France AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, Laboratoire de Biochimie, Paris, France AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, Département de radiologie, Paris, France Department of Anesthesia and Peri-operative Care, Division of Critical Care Medicine, University of California, San Francisco, CA, USA Assistance Publique–Hôpitaux de Paris (AP-HP), Groupe Hospitalier Cochin Port Royal, DMU Cancérologie et spécialités médico-chirurgicales, Service de Maladie du Foie, Paris, France

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Leonhardt S, Jürgensen C, Frohme J, Grajecki D, Adler A, Sigal M, Leonhardt J, Voll JM, Kruse JM, Körner R, Eckardt KU, Janssen HJ, Gebhardt V, Schmittner MD, Frey C, Müller-Ide H, Bauer M, Thibeault C, Kurth F, Sander LE, Müller T, Tacke F. Hepatobiliary long-term consequences of COVID-19: dramatically increased rate of secondary sclerosing cholangitis in critically ill COVID-19 patients. Hepatol Int 2023;17:1610-1625. [PMID: 37119516 PMCID: PMC10148013 DOI: 10.1007/s12072-023-10521-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 03/13/2023] [Indexed: 05/01/2023]

Affiliation(s)

Silke Leonhardt Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.
Christian Jürgensen Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Mitte, Charitéplatz 1, 10117, Berlin, Germany
Josephine Frohme Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany
Donata Grajecki Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany
Andreas Adler Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany
Michael Sigal Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany
Julia Leonhardt Department of Anesthesiology and Intensive Care Medicine, University Hospital Jena and Center for Sepsis Control and Care, University Hospital Jena, Am Klinikum 1, 07747, Jena, Germany
Julian M Voll Department of Anesthesiology and Intensive Care Medicine, University Hospital Jena and Center for Sepsis Control and Care, University Hospital Jena, Am Klinikum 1, 07747, Jena, Germany
Jan Matthias Kruse Department of Nephrology and Medical Intensive Care, Charité-Universitäts-Medizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
Roland Körner Department of Nephrology and Medical Intensive Care, Charité-Universitäts-Medizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
Kai-Uwe Eckardt Department of Nephrology and Medical Intensive Care, Charité-Universitäts-Medizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
Hans-Joachim Janssen Department of Anesthesiology, Intensive Care and Pain Medicine, BG Klinikum Unfallkrankenhaus Berlin gGmbH, Warener Strasse 7, 12683, Berlin, Germany
Volker Gebhardt Department of Anesthesiology, Intensive Care and Pain Medicine, BG Klinikum Unfallkrankenhaus Berlin gGmbH, Warener Strasse 7, 12683, Berlin, Germany
Marc D Schmittner Department of Anesthesiology, Intensive Care and Pain Medicine, BG Klinikum Unfallkrankenhaus Berlin gGmbH, Warener Strasse 7, 12683, Berlin, Germany
Christian Frey Department of Anesthesiology and Intensive Care, Bundeswehrkrankenhaus, Berlin, Scharnhorststrasse 13, 10115, Berlin, Germany
Hendrik Müller-Ide Department of Internal Medicine, Cardiology and Medical Intensive Care, Vivantes Hospital Spandau, Neue Bergstrasse 6, 13585, Berlin, Germany
Michael Bauer Department of Anesthesiology and Intensive Care Medicine, University Hospital Jena and Center for Sepsis Control and Care, University Hospital Jena, Am Klinikum 1, 07747, Jena, Germany
Charlotte Thibeault Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany
Florian Kurth Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany
Leif Erik Sander Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany German Centre for Lung Research (DZL), Gießen, Germany
Tobias Müller Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany
Frank Tacke Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany

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Leonhardt S, Baumann S, Jürgensen C, Hüter L, Leonhardt J. Role of intravenous ketamine in the pathogenesis of secondary sclerosing cholangitis in critically ill patients: perpetrator or innocent bystander? Answers provided by forensic toxicology. Intensive Care Med 2023;49:1549-1551. [PMID: 37943301 PMCID: PMC10709220 DOI: 10.1007/s00134-023-07257-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/16/2023] [Indexed: 11/10/2023]

Kim HY, Lee SS. Post-COVID-19 Cholangiopathy: Clinical and Radiologic Findings. Korean J Radiol 2023;24:1167-1171. [PMID: 37899526 PMCID: PMC10613835 DOI: 10.3348/kjr.2023.0832] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 09/18/2023] [Accepted: 09/18/2023] [Indexed: 10/31/2023] Open

Grama A, Mititelu A, Sîrbe C, Benţa G, Pop TL. Immune-mediated cholangiopathies in children: the need to better understand the pathophysiology for finding the future possible treatment targets. Front Immunol 2023;14:1206025. [PMID: 37928553 PMCID: PMC10623351 DOI: 10.3389/fimmu.2023.1206025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Accepted: 09/28/2023] [Indexed: 11/07/2023] Open

Abstract

Cholangiopathies are defined as focal or extensive damage of the bile ducts. According to the pathogenetic mechanism, it may be immune-mediated or due to genetic, infectious, toxic, vascular, and obstructive causes. Their chronic evolution is characterized by inflammation, obstruction of bile flow, cholangiocyte proliferation, and progression toward fibrosis and cirrhosis. Immune-mediated cholangiopathies comprise primary sclerosing cholangitis (PSC), autoimmune cholangitis and IgG4-associated cholangitis in adults and biliary atresia (BA), neonatal sclerosing cholangitis (NSC) in children. The main purpose of this narrative review was to highlight the similarities and differences among immune-mediated cholangiopathies, especially those frequent in children in which cholangiocyte senescence plays a key role (BA, NSC, and PSC). These three entities have many similarities in terms of clinical and histopathological manifestations, and the distinction between them can be hard to achieve. In BA, bile duct destruction occurs due to aggression of the biliary cells due to viral infections or toxins during the intrauterine period or immediately after birth. The consequence is the activation of the immune system leading to severe inflammation and fibrosis of the extrahepatic biliary tract, lumen stenosis, and impairment of the biliary flow. PSC is characterized by inflammation and fibrosis of intra- and extrahepatic bile ducts, leading to secondary biliary cirrhosis. It is a multifactorial disease that occurs because of genetic predisposition [human leukocyte antigen (HLA) and non-HLA haplotypes], autoimmunity (cellular immune response, autoantibodies, association with inflammatory bowel disease), environmental factors (infections or toxic bile), and host factors (intestinal microbiota). NSC seems to be a distinct subgroup of childhood PSC that appears due to the interaction between genetic predisposition (HLA B8 and DR3) and the disruption of the immune system, validated by elevated IgG levels or specific antibodies [antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA)]. Currently, the exact mechanism of immune cholangiopathy is not fully understood, and further data are required to identify individuals at high risk of developing these conditions. A better understanding of the immune mechanisms and pathophysiology of BA, NSC, and PSC will open new perspectives for future treatments and better methods of preventing severe evolution.

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Lim JK, Njei B. Clinical and Histopathological Discoveries in Patients with Hepatic Injury and Cholangiopathy Who Have Died of COVID-19: Insights and Opportunities for Intervention. Hepat Med 2023;15:151-164. [PMID: 37814605 PMCID: PMC10560482 DOI: 10.2147/hmer.s385133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 09/28/2023] [Indexed: 10/11/2023] Open

Rasheed MA, Ballotin VR, Bigarella LG, Soldera J. Post-COVID-19 cholangiopathy: Systematic review. World J Methodol 2023;13:296-322. [PMID: 37771872 PMCID: PMC10523251 DOI: 10.5662/wjm.v13.i4.296] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 06/07/2023] [Accepted: 08/23/2023] [Indexed: 09/20/2023] Open

Abstract

BACKGROUND

The coronavirus disease 2019 (COVID-19) pandemic has had a profound impact on global health, primarily characterized by severe respiratory illness. However, emerging evidence suggests that COVID-19 can also lead to secondary sclerosing cholangitis (SC), referred to as post-COVID-19 cholangiopathy.

AIM

To synthesize currently reported cases to assess the current state of knowledge on post-COVID-19 cholangiopathy.

METHODS

Medical Subject Headings and Health Sciences Descriptors were used to retrieve relevant studies, which were combined using Boolean operators. Searches were conducted on electronic databases including Scopus, Web of Science, and MEDLINE (PubMed). Studies published in English, Spanish, or Portuguese were included, with no restrictions on the publication date. Additionally, the reference lists of retrieved studies were manually searched. Simple descriptive analyses were used to summarize the results. Then the data were extracted and assessed based on Reference Citation Analysis (https://www.referencecitationanalysis.com/).

RESULTS

The initial search yielded a total of 192 articles. After screening, 85 articles were excluded due to duplication, leaving 107 articles for further review. Of these, 63 full-length articles met the inclusion criteria and were included in the analyses. Most of the patients were male and exhibited elevated liver function tests (93.8%). Magnetic resonance imaging revealed duct thickening with contrast enhancement (47.7%), as well as beading of the intrahepatic ducts (45.7%) with peribiliary contrast enhancement on diffusion (28.7%). Liver biopsy results confirmed SC in most cases (74.4%). Sixteen patients underwent liver transplantation, with three experiencing successful outcomes.

CONCLUSION

Post-COVID-19 cholangiopathy is a serious condition that is expected to become increasingly concerning in the coming years, particularly considering long COVID syndromes. Although liver transplantation has been proposed as a potential treatment option, more research is necessary to establish its efficacy and explore other potential treatments.

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Bartoli A, Cursaro C, Seferi H, Andreone P. Secondary Sclerosing Cholangitis After SARS-CoV2: ICU Ketamine Use or Virus-Specific Biliary Tropism and Injury in the Context of Biliary Ischemia in Critically Ill Patients? Hepat Med 2023;15:93-112. [PMID: 37547355 PMCID: PMC10404108 DOI: 10.2147/hmer.s384220] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 07/12/2023] [Indexed: 08/08/2023] Open

Abstract

Purpose

From the beginning of the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV2) pandemic, different cases of a cholangiopathy with features of secondary sclerosing cholangitis in critically ill patients (SSC-CIP) have been reported. Patients developing it are generally recovering from severe Coronavirus disease 19 (COVID-19) and required intensive care unit (ICU) admission and mechanical ventilation. Many of them have been administered with ketamine during their ICU stay. The pathogenesis of this novel disease is still debated, and, since prognosis is poor, efforts are needed in order to better understand it.

Patients and Methods

In this review, we focused our attention on COVID-19 SSC clinical, imaging, and histology findings in order to clarify the different pathogenetic options, particularly in regard of the ischemic-direct viral damage and ketamine-related theories, beginning with a recapitulation of SSC-CIP and ketamine-induced cholangiopathy in abusers. The research has been conducted using PubMed and Google Scholar databases. Key-words were "Secondary Sclerosing Cholangiopathy", "SSC-CIP", "Secondary Sclerosing Cholangiopathy in critically ill patients", "Ketamine and cholangiopathy", "Ketamine abusers and liver disease", "Ketamine-related cholangiopathy", "SARS-CoV2 infection and liver disease", "post Covid-19 secondary sclerosing cholangitis", "Covid-19 cholangiopathy".

Results

Many authors, based on the clinical, histological, imaging, and prognostic features of the disease, have pointed out the similarities between post COVID-19 SSC and SSC-CIP; however, peculiar features in the former were not previously observed. Therefore, a direct viral cytopathic action and SARS-CoV2-related coagulopathy are considered the most likely causes. On the other hand, ketamine, with the available data, cannot be surely linked as the main determinant cause of cholangiopathy. Moreover, ketamine-induced cholangitis (KIC) presentation is different from post COVID-19 SSC. Its role as a cofactor precipitating the disease cannot be ruled out.

Conclusion

Post COVID-19 SSC is a rare clinical entity following severe COVID-19 disease. The most accepted theory is that a sum of different insults determines the disease: biliary ischemia, direct viral damage, toxic bile, possibly worsened by ketamine and hyperinflammation due to the cytokine storm. Given the severe prognosis of the disease, with persistent cholangiopathy, organ failure, and orthotopic liver transplantation (OLT), further study on this novel clinical entity is needed.

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Zippi M, Fiorino S, Hong W, de Biase D, Gallo CG, Grottesi A, Centorame A, Crispino P. Post-COVID-19 cholangiopathy: A systematic review. World J Meta-Anal 2023;11:229-237. [DOI: 10.13105/wjma.v11.i5.229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/28/2023] Open

Schep LJ, Slaughter RJ, Watts M, Mackenzie E, Gee P. The clinical toxicology of ketamine. Clin Toxicol (Phila) 2023:1-14. [PMID: 37267048 DOI: 10.1080/15563650.2023.2212125] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 05/01/2023] [Accepted: 05/04/2023] [Indexed: 06/04/2023]

Abstract

INTRODUCTION

Ketamine is a pharmaceutical drug possessing both analgesic and anaesthetic properties. As an anaesthetic, it induces anaesthesia by producing analgesia with a state of altered consciousness while maintaining airway tone, respiratory drive, and hemodynamic stability. At lower doses, it has psychoactive properties and has gained popularity as a recreational drug.

OBJECTIVES

To review the epidemiology, mechanisms of toxicity, pharmacokinetics, clinical features, diagnosis and management of ketamine toxicity.

METHODS

Both OVID MEDLINE (January 1950-April 2023) and Web of Science (1900-April 2023) databases were searched using the term "ketamine" in combination with the keywords "pharmacokinetics", "kinetics", "poisoning", "poison", "toxicity", "ingestion", "adverse effects", "overdose", and "intoxication". Furthermore, bibliographies of identified articles were screened for additional relevant studies. These searches produced 5,268 non-duplicate citations; 185 articles (case reports, case series, pharmacokinetic studies, animal studies pertinent to pharmacology, and reviews) were considered relevant. Those excluded were other animal investigations, therapeutic human clinical investigations, commentaries, editorials, cases with no clinical relevance and post-mortem investigations.

EPIDEMIOLOGY

Following its introduction into medical practice in the early 1970s, ketamine has become a popular recreational drug. Its use has become associated with the dance culture, electronic and dubstep dance events.

MECHANISM OF ACTION

Ketamine acts primarily as a non-competitive antagonist on the glutamate N-methyl-D-aspartate receptor, causing the loss of responsiveness that is associated with clinical ketamine dissociative anaesthesia.

PHARMACOKINETICS

Absorption of ketamine is rapid though the rate of uptake and bioavailability is determined by the route of exposure. Ketamine is metabolized extensively in the liver. Initially, both isomers are metabolized to their major active metabolite, norketamine, by CYP2B6, CYP3A4 and CYP2C9 isoforms. The hydroxylation of the cyclohexan-1-one ring of norketamine to the three positional isomers of hydroxynorketamine occurs by CYP2B6 and CYP2A6. The dehydronorketamine metabolite occurs either by direct dehydrogenation from norketamine via CYP2B6 metabolism or non-enzymatic dehydration of hydroxynorketamine. Norketamine, the dehydronorketamine isomers, and hydroxynorketamine have pharmacological activity. The elimination of ketamine is primarily by the kidneys, though unchanged ketamine accounts for only a small percentage in the urine. The half-life of ketamine in humans is between 1.5 and 5 h.

CLINICAL FEATURES

Acute adverse effects following recreational use are diverse and can include impaired consciousness, dizziness, irrational behaviour, hallucinations, abdominal pain and vomiting. Chronic use can result in impaired verbal information processing, cystitis and cholangiopathy.

DIAGNOSIS

The diagnosis of acute ketamine intoxication is typically made on the basis of the patient's history, clinical features, such as vomiting, sialorrhea, or laryngospasm, along with neuropsychiatric features. Chronic effects of ketamine toxicity can result in cholangiopathy and cystitis, which can be confirmed by endoscopic retrograde cholangiopancreatography and cystoscopy, respectively.

MANAGEMENT

Treatment of acute clinical toxicity is predominantly supportive with empiric management of specific adverse effects. Benzodiazepines are recommended as initial treatment to reduce agitation, excess neuromuscular activity and blood pressure. Management of cystitis is multidisciplinary and multi-tiered, following a stepwise approach of pharmacotherapy and surgery. Management of cholangiopathy may require pain management and, where necessary, biliary stenting to alleviate obstructions. Chronic effects of ketamine toxicity are typically reversible, with management focusing on abstinence.

CONCLUSIONS

Ketamine is a dissociative drug employed predominantly in emergency medicine; it has also become popular as a recreational drug. Its recreational use can result in acute neuropsychiatric effects, whereas chronic use can result in cystitis and cholangiopathy.

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Kang D, Kim HS, Han S, Lee Y, Kim YP, Lee DY, Lee J. A local water molecular-heating strategy for near-infrared long-lifetime imaging-guided photothermal therapy of glioblastoma. Nat Commun 2023;14:2755. [PMID: 37179387 PMCID: PMC10183012 DOI: 10.1038/s41467-023-38451-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 05/04/2023] [Indexed: 05/15/2023] Open

Yadlapati S, Jarrett SA, Baik D, Chaaya A. COVID-19 related biliary injury: A review of recent literature. World J Gastroenterol 2023;29:2127-2133. [PMID: 37122603 PMCID: PMC10130971 DOI: 10.3748/wjg.v29.i14.2127] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 03/11/2023] [Accepted: 03/21/2023] [Indexed: 04/13/2023] Open

Toxicity patterns associated with chronic ketamine exposure. TOXICOLOGIE ANALYTIQUE ET CLINIQUE 2023. [DOI: 10.1016/j.toxac.2023.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/08/2023]

Ippolito D, Maino C, Vernuccio F, Cannella R, Inchingolo R, Dezio M, Faletti R, Bonaffini PA, Gatti M, Sironi S. Liver involvement in patients with COVID-19 infection: A comprehensive overview of diagnostic imaging features. World J Gastroenterol 2023;29:834-850. [PMID: 36816623 PMCID: PMC9932422 DOI: 10.3748/wjg.v29.i5.834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 12/06/2022] [Accepted: 01/20/2023] [Indexed: 02/06/2023] Open

Henrie J, Gerard L, Declerfayt C, Lejeune A, Baldin P, Robert A, Laterre PF, Hantson P. Profile of liver cholestatic biomarkers following prolonged ketamine administration in patients with COVID-19. BMC Anesthesiol 2023;23:44. [PMID: 36750971 PMCID: PMC9902832 DOI: 10.1186/s12871-023-02006-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 02/02/2023] [Indexed: 02/09/2023] Open

Zippi M, Fiorino S, Hong W, de Biase D, Gallo CG, Grottesi A, Centorame A, Crispino P. Post-COVID-19 cholangiopathy: A systematic review. World J Meta-Anal 2023;11:29-37. [DOI: 10.13105/wjma.v11.i1.29] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 10/13/2022] [Accepted: 11/23/2022] [Indexed: 01/11/2023] Open

Schmid S, Kandulski A, Müller-Schilling M. COVID-19 und Lebererkrankungen. DIE GASTROENTEROLOGIE 2023;18:107-114. [PMCID: PMC9993380 DOI: 10.1007/s11377-023-00680-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 02/02/2023] [Indexed: 01/03/2025]

Abstract

Bis zu 53 % der PatientInnen mit Coronavirus Disease 2019 (COVID-19) weisen eine hepatische Beteiligung auf. Durch die Expression der Hauptzielstruktur für „severe acute respiratory syndrome coronavirus type 2“ (SARS-CoV-2), des Angiotensin-converting-Enzym-2(ACE2)-Rezeptors, auch auf Cholangiozyten, sinusoidalen Endothelzellen und Hepatozyten kann es zu einer direkten Schädigung der Leber kommen. Ferner spielt eine indirekte (nicht durch Rezeptoren vermittelte) Schädigung der Leber im Rahmen von COVID-19 durch eine schwere systemische Inflammation mit Zytokinsturm, hepatischen Thrombosen und einer systemischen Hypoxie eine wichtige Rolle. Bei COVID-19 gelten Leberwerte als wichtige Prädiktoren für die Prognose der PatientInnen. Wichtig ist es hierbei Differenzialdiagnosen für die Leberwerterhöhung, wie andere Virusinfektionen, medikamentös-toxisch induzierte Leberschädigung sowie autoimmune, metabolische und andere Lebererkrankungen, abzuklären. Von hoher klinischer Relevanz für die Behandlung kritisch kranker PatientInnen auf der Intensivstation ist das Krankheitsbild der „secondary sclerosing cholangitis in critically ill patients“ (SSC-CIP). Hierfür sind unter anderem hochdosierte Katecholamine, eine Beatmung mit hohem positivem endexspiratorischem Druck (PEEP) und die extrakorporale Membranoxygenierung (ECMO) Risikofaktoren. Eine frühe Diagnose dieser Erkrankung und Behandlung mittels interventioneller endoskopischer retrograder Cholangiographie (ERC) ist hierbei von entscheidender Bedeutung. Auch sollte eine Lebertransplantation evaluiert werden. Bei einer COVID-19-Erkrankung treten Fälle mit SSC, sog. COVID-SSC, auf. Die COVID-SSC und die SSC-CIP sind im klinischen Phänotyp, Risikofaktoren, Prognose und transplantatfreien Überleben vergleichbar. PatientInnen mit vorbestehender Lebererkrankung haben kein erhöhtes Risiko für eine Infektion mit SARS-CoV‑2, erkranken jedoch schwerer an COVID-19 als PatientInnen ohne Lebervorerkrankungen. Bei PatientInnen mit einer vorbestehenden Leberzirrhose kann eine SARS-CoV-2-Infektion ein akut-auf-chronisches Leberversagen (ACLF) induzieren. Hierbei handelt es sich um ein Krankheitsbild mit einer sehr hohen Mortalität, das im Rahmen einer intensivmedizinischen Behandlung therapiert werden muss.

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Polyzogopoulou E, Amoiridou P, Abraham TP, Ventoulis I. Acute liver injury in COVID-19 patients hospitalized in the intensive care unit: Narrative review. World J Gastroenterol 2022;28:6662-6688. [PMID: 36620339 PMCID: PMC9813941 DOI: 10.3748/wjg.v28.i47.6662] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 11/14/2022] [Accepted: 12/05/2022] [Indexed: 12/19/2022] Open

Abstract

In recent years, humanity has been confronted with a global pandemic due to coronavirus disease 2019 (COVID-19), which has caused an unprecedented health and economic crisis worldwide. Apart from the respiratory symptoms, which are considered the principal manifestations of COVID-19, it has been recognized that COVID-19 constitutes a systemic inflammatory process affecting multiple organ systems. Across the spectrum of organ involvement in COVID-19, acute liver injury (ALI) has been gradually gaining increasing attention by the international scientific community. COVID-19 associated liver impairment can affect a considerable proportion of COVID-19 patients and seems to correlate with the severity of the disease course. Indeed, COVID-19 patients hospitalized in the intensive care unit (ICU) run a greater risk of developing ALI due to the severity of their clinical condition and in the context of multi-organ failure. The putative pathophysiological mechanisms of COVID-19 induced ALI in ICU patients remain poorly understood and appear to be multifactorial in nature. Several theories have been proposed to explain the occurrence of ALI in the ICU setting, such as hypoperfusion and ischemia due to hemodynamic instability, passive liver congestion as a result of congestive heart failure, ischemia-reperfusion injury, hypoxia due to respiratory failure, mechanical ventilation itself, sepsis and septic shock, cytokine storm, endotheliitis with concomitant coagulopathy, drug-induced liver injury, parenteral nutrition and direct cytopathic viral effect. It should be noted that no specific therapy for COVID-19 induced ALI exists. Therefore, the therapeutic approach lies in preventive measures and is exclusively supportive once ALI ensues. The aim of the current review is to scrutinize the existing evidence on COVID-19 associated ALI in ICU patients, explore its clinical implications, shed light on the underlying pathophysiological mechanisms and propose potential therapeutic approaches. Ongoing research on the particular scientific field will further elucidate the pathophysiology behind ALI and address unresolved issues, in the hope of mitigating the tremendous health consequences imposed by COVID-19 on ICU patients.

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Heucke N, Keitel V. COVID-19-associated cholangiopathy: What is left after the virus has gone? Hepatology 2022;76:1560-1562. [PMID: 35822670 PMCID: PMC9350171 DOI: 10.1002/hep.32668] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 07/01/2022] [Indexed: 12/08/2022]

Kulkarni AV, Khelgi A, Sekaran A, Reddy R, Sharma M, Tirumalle S, Gora BA, Somireddy A, Reddy J, Menon B, Reddy DN, Rao NP. Post-COVID-19 Cholestasis: A Case Series and Review of Literature. J Clin Exp Hepatol 2022;12:1580-1590. [PMID: 35719861 PMCID: PMC9187855 DOI: 10.1016/j.jceh.2022.06.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 06/06/2022] [Indexed: 12/12/2022] Open

Abstract

BACKGROUND

Coronavirus disease-2019 (COVID-19) cholangiopathy is a recently known entity. There are very few reports of liver transplantation (LT) for COVID-19-induced cholangiopathy. It is well known that vaccines can prevent severe disease and improve outcomes. However, there are no reports on the impact of COVID-19 vaccines on cholestasis. Therefore, we aimed to compare the course and outcome of patients who developed cholestasis following COVID-19 infection among vaccinated and unvaccinated individuals. Methods: Patients diagnosed with post-COVID cholestasis during the pandemic were included in the study after excluding other causes of cholestasis.

RESULTS

Eight unvaccinated and seven vaccinated individuals developed cholestasis following COVID-19 infection. Baseline demographics, presentation, severity, and management of COVID-19 were similar in both groups. However, patients in the unvaccinated group had a protracted course. The peak ALP was 312 (239-517) U/L in the vaccinated group and 571.5 (368-1058) U/L in the unvaccinated group (P = 0.02). Similarly, the peak γ-glutamyl transpeptidase values were lower in the vaccinated (325 [237-600] U/L) than in the unvaccinated group (832 [491-1640] U/L; P = 0.004). However, the peak values of total bilirubin, transaminases, and INR were similar in both groups. Five patients developed ascites gradually in the unvaccinated group whereas none in the vaccinated group developed ascites. Plasma exchange was done in five patients, and two were successfully bridged to living donor LT in the unvaccinated group. Only two patients recovered with conservative management in the unvaccinated group, whereas all recovered with conservative management in the vaccinated group. The other four patients in the unvaccinated group were planned for LT.

CONCLUSION

Post-COVID-19 cholestasis is associated with high morbidity and mortality, meriting early identification and appropriate management. Vaccination can modify the course of severe COVID-19 infection and improve outcomes.

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Post-Covid- 19 Cholangiopathy:A Systematic Review. J Clin Exp Hepatol 2022;13:489-499. [PMID: 36337085 PMCID: PMC9618303 DOI: 10.1016/j.jceh.2022.10.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 10/07/2022] [Accepted: 10/23/2022] [Indexed: 11/07/2022] Open

Impact of COVID-19 on the liver and on the care of patients with chronic liver disease, hepatobiliary cancer, and liver transplantation: An updated EASL position paper. J Hepatol 2022;77:1161-1197. [PMID: 35868584 PMCID: PMC9296253 DOI: 10.1016/j.jhep.2022.07.008] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 07/06/2022] [Accepted: 07/06/2022] [Indexed: 02/06/2023]

Schwarz S, Lang C, Harlander M, Štupnik T, Slambrouck JV, Ceulemans LJ, Ius F, Gottlieb J, Kuhnert S, Hecker M, Aigner C, Kneidinger N, Verschuuren EAM, Smits JM, Tschernko E, Schaden E, Faybik P, Markstaller K, Trauner M, Jaksch P, Hoetzenecker K. Gamma-glutamyltransferase is a strong predictor of secondary sclerosing cholangitis after lung transplantation for COVID-19 ARDS. J Heart Lung Transplant 2022;41:1501-1510. [PMID: 35907758 PMCID: PMC9249665 DOI: 10.1016/j.healun.2022.06.020] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 06/20/2022] [Accepted: 06/24/2022] [Indexed: 01/31/2023] Open

Affiliation(s)

Stefan Schwarz Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
Christian Lang Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
Matevz Harlander Department of Pulmonary Diseases, University Medical Center, Ljubljana, Slovenia
Tomaz Štupnik Department of Thoracic Surgery, University Medical Center, Ljubljana, Slovenia
Jan Van Slambrouck Department of Thoracic Surgery, Lab of BREATHE, University Hospitals Leuven, KU Leuven, Leuven, Belgium
Laurens J. Ceulemans Department of Thoracic Surgery, Lab of BREATHE, University Hospitals Leuven, KU Leuven, Leuven, Belgium
Fabio Ius Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Hannover, Germany
Jens Gottlieb Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany
Stefan Kuhnert Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine II, University Hospital Giessen, Justus Liebig University of Giessen, Giessen, Germany
Matthias Hecker Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine II, University Hospital Giessen, Justus Liebig University of Giessen, Giessen, Germany
Clemens Aigner Department of Thoracic Surgery, West German Cancer Center, University Medicine Essen - Ruhrlandklinik, Essen, Germany
Nikolaus Kneidinger Department of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center (CPC), Member of German Center for Lung Research (DZL), Munich, Germany
Erik AM. Verschuuren Department of Respiratory Diseases, Tuberculosis and Lung Transplantation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
Jacqueline M. Smits Eurotransplant International Foundation, Leiden, The Netherlands
Edda Tschernko Division of Cardiac, Thoracic and Vascular Anesthesia and Intensive Care, Medical University of Vienna, Vienna, Austria
Eva Schaden Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria
Peter Faybik Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria
Klaus Markstaller Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria
Michael Trauner Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
Peter Jaksch Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
Konrad Hoetzenecker Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria,⁎Reprint requests: Konrad Hoetzenecker, MD PhD, Division of Thoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna. Telephone: +43-1-404-005-6440. Fax: +43-1-404-005-1000

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Mayorquín-Aguilar JM, Lara-Reyes A, Revuelta-Rodríguez LA, Flores-García NC, Ruiz-Margáin A, Jiménez-Ferreira MA, Macías-Rodríguez RU. Secondary sclerosing cholangitis after critical COVID-19: Three case reports. World J Hepatol 2022;14:1678-1686. [PMID: 36157873 PMCID: PMC9453459 DOI: 10.4254/wjh.v14.i8.1678] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 04/04/2022] [Accepted: 08/15/2022] [Indexed: 02/06/2023] Open

Secondary sclerosing cholangitis after COVID-19 pneumonia: a report of two cases and review of the literature. Clin J Gastroenterol 2022;15:1124-1129. [PMID: 35953614 PMCID: PMC9371366 DOI: 10.1007/s12328-022-01687-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 08/01/2022] [Indexed: 01/08/2023]

Faruqui S, Shanbhogue K, Jacobson IM. Biliary Tract Injury in Patients With COVID-19: A Review of the Current Literature. Gastroenterol Hepatol (N Y) 2022;18:380-387. [PMID: 36397771 PMCID: PMC9666809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]

Shih AR, Hatipoglu D, Wilechansky R, Goiffon R, Deshpande V, Misdraji J, Chung RT. Persistent Cholestatic Injury and Secondary Sclerosing Cholangitis in COVID-19 Patients. Arch Pathol Lab Med 2022;146:1184-1193. [PMID: 35657750 DOI: 10.5858/arpa.2021-0605-sa] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/01/2022] [Indexed: 02/06/2023]

Abstract

CONTEXT.–

Coronavirus disease 2019 (COVID-19) has been associated with liver injury, and a small subset of patients recovering from severe disease have shown persistent markedly elevated liver biochemistries for months after infection.

OBJECTIVE.–

To characterize persistent biliary injury after COVID-19.

DESIGN.–

A search of the pathology archives identified 7 post-COVID-19 patients with persistent biliary injury, and the clinical, radiologic, and pathologic features were assessed.

RESULTS.–

All patients in this cohort presented with respiratory symptoms and had a complicated clinical course with acute elevation of liver biochemistries. Alkaline phosphatase (ALP) was markedly and persistently elevated after discharge (median peak ALP: 1498 IU/L, at a median of 84 days from diagnosis). Magnetic resonance cholangiopancreatography (MRCP) showed 3 patients with irregularity, stricturing, and dilatation of intrahepatic ducts; no radiographic abnormalities were identified in the remaining 4 patients. Liver biopsies showed mild portal changes with features of cholestatic injury in 4 patients (bile duct injury and canalicular cholestasis) and marked biliary obstruction in 2 patients (profound cholestasis, ductular reaction, and bile infarcts), but no SARS-CoV-2 ribonucleic acid (RNA) was identified on in-situ hybridization. On follow-up, most patients had minimal intervention and showed marked improvement of liver biochemistries but with mild persistent elevation of ALP.

CONCLUSIONS.–

A subset of critically ill COVID-19 patients demonstrates marked and persistent cholestatic injury, with radiographic and histologic evidence of secondary sclerosing cholangitis, suggesting that cholestatic liver disease and secondary sclerosing cholangitis may be long-term sequelae of COVID-19 acute illness as a longstanding manifestation of critical illness.

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Long-term ketamine infusion-induced cholestatic liver injury in COVID-19-associated acute respiratory distress syndrome. Crit Care 2022;26:148. [PMID: 35606831 PMCID: PMC9125956 DOI: 10.1186/s13054-022-04019-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Accepted: 05/15/2022] [Indexed: 12/24/2022] Open

Abstract

Background

A higher-than-usual resistance to standard sedation regimens in COVID-19 patients suffering from acute respiratory distress syndrome (ARDS) has led to the frequent use of the second-line anaesthetic agent ketamine. Simultaneously, an increased incidence of cholangiopathies in mechanically ventilated patients receiving prolonged infusion of high-dose ketamine has been noted. Therefore, the objective of this study was to investigate a potential dose–response relationship between ketamine and bilirubin levels.

Methods

Post hoc analysis of a prospective observational cohort of patients suffering from COVID-19-associated ARDS between March 2020 and August 2021. A time-varying, multivariable adjusted, cumulative weighted exposure mixed-effects model was employed to analyse the exposure–effect relationship between ketamine infusion and total bilirubin levels.

Results

Two-hundred forty-three critically ill patients were included into the analysis. Ketamine was infused to 170 (70%) patients at a rate of 1.4 [0.9–2.0] mg/kg/h for 9 [4–18] days. The mixed-effects model revealed a positively correlated infusion duration–effect as well as dose–effect relationship between ketamine infusion and rising bilirubin levels (p < 0.0001). In comparison, long-term infusion of propofol and sufentanil, even at high doses, was not associated with increasing bilirubin levels (p = 0.421, p = 0.258). Patients having received ketamine infusion had a multivariable adjusted competing risk hazard of developing a cholestatic liver injury during their ICU stay of 3.2 [95% confidence interval, 1.3–7.8] (p = 0.01).

Conclusions

A causally plausible, dose–effect relationship between long-term infusion of ketamine and rising total bilirubin levels, as well as an augmented, ketamine-associated, hazard of cholestatic liver injury in critically ill COVID-19 patients could be shown. High-dose ketamine should be refrained from whenever possible for the long-term analgosedation of mechanically ventilated COVID-19 patients.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13054-022-04019-8.

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Drug-induced bile duct injury: new agents, new mechanisms. Curr Opin Gastroenterol 2022;38:83-88. [PMID: 34931623 DOI: 10.1097/mog.0000000000000813] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]

Bartoli A, Cursaro C, Andreone P. Severe acute respiratory syndrome coronavirus-2-associated cholangiopathies. Curr Opin Gastroenterol 2022;38:89-97. [PMID: 35098930 PMCID: PMC8815639 DOI: 10.1097/mog.0000000000000808] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]

Severe Cholestatic Hepatitis Secondary to SARS-CoV-2. ACG Case Rep J 2022;9:e00753. [PMID: 35359752 PMCID: PMC8963841 DOI: 10.14309/crj.0000000000000753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 11/17/2021] [Indexed: 12/15/2022] Open

Cotter S, Wong J, Gada N, Gill R, Jones SC, Chai G, Foster D, Avigan M, Mundkur M. Repeated or Continuous Medically Supervised Ketamine Administration Associated with Hepatobiliary Adverse Events: A Retrospective Case Series. Drug Saf 2021;44:1365-1374. [PMID: 34699023 PMCID: PMC8546385 DOI: 10.1007/s40264-021-01120-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/12/2021] [Indexed: 01/02/2023]

Abstract

Introduction

Emerging off-label medical uses of ketamine for the treatment of persistent conditions such as depression and chronic pain often require repeated administration. Cases reported by other countries suggest that long-term and repeated exposure to ketamine may be associated with several risks, including but not limited to hepatobiliary damage.

Objective

We aimed (1) to characterize the association between repeated administration of ketamine for off-label medical use and hepatobiliary events and (2) to describe recent trends in the use of ketamine across different clinical settings.

Methods

We conducted a retrospective case series analysis, utilizing reports identified from the US Food and Drug Administration Adverse Event Reporting System database as well as the medical literature. We included all cases reported through July 2018 describing both repeated exposure to ketamine in a hospital or ambulatory setting and a hepatobiliary adverse event. We excluded cases describing ketamine abuse. We identified adverse hepatobiliary events using the Medical Dictionary for Regulatory Activities (MedDRA^®) and summarized various case characteristics including: patient demographics, route of ketamine administration, dose, time to onset of event, type of event, and pre-existing risk factors for hepatobiliary disease. To assess trends in the demand for ketamine, we used IQVIA, National Sales Perspectives™ to provide the nationally estimated number of vials sold for ketamine from the manufacturer to all US channels of distribution from 2013 through 2017.

Results

We identified 14 unique cases that met selection criteria with 21 hepatobiliary adverse events including liver enzyme elevation in all cases, biliary dilation with liver cirrhosis (n = 1), biliary dilation with cholangitis (n = 1), and pericholeductal fibrosis (n = 1). Most cases received ketamine for the treatment of complex regional pain syndrome or chronic pain. In cases with a reported time to onset, the majority of events occurred within 4 days. The nationally estimated number of ketamine vials sold in the USA from manufacturers to various channels of distribution increased from 1.2 million in 2013 to 2.1 million in 2017.

Conclusions

We report an association between repeated or continuous administration of ketamine and hepatobiliary adverse events. Increased awareness among clinicians may mitigate these adverse outcomes, especially in the context of growing ketamine sales.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40264-021-01120-9.

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Affiliation(s)

Samantha Cotter Affiliated with the Office of Surveillance and Epidemiology, Office of Pharmacovigilance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD, 20993, USA.
Jennie Wong Affiliated with the Office of Surveillance and Epidemiology, Office of Pharmacovigilance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD, 20993, USA
Neha Gada Affiliated with the Office of Surveillance and Epidemiology, Office of Pharmacovigilance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD, 20993, USA
Rajdeep Gill Affiliated with the Office of Surveillance and Epidemiology, Office of Pharmacovigilance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD, 20993, USA
S Christopher Jones Affiliated with the Office of Surveillance and Epidemiology, Office of Pharmacovigilance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD, 20993, USA
Grace Chai Affiliated with the Office of Surveillance and Epidemiology, Office of Pharmacovigilance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD, 20993, USA
Daniel Foster Affiliated with the Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD, 20993, USA
Mark Avigan Affiliated with the Office of Surveillance and Epidemiology, Office of Pharmacovigilance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD, 20993, USA
Mallika Mundkur Affiliated with the Office of Surveillance and Epidemiology, Office of Pharmacovigilance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD, 20993, USA

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Mallet V. Reply to: "Progressive cholangiopathy in COVID-19 patients: Other possible diagnoses than ketamine-induced cholangiopathy should be considered". J Hepatol 2021;75:990-992. [PMID: 34174378 PMCID: PMC8223115 DOI: 10.1016/j.jhep.2021.06.024] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 06/09/2021] [Indexed: 12/19/2022]

Deltenre P, Moreno C, Trépo E. Progressive cholangiopathy in COVID-19 patients: Other possible diagnoses than ketamine-induced cholangiopathy should be considered. J Hepatol 2021;75:989-990. [PMID: 33753153 PMCID: PMC7977066 DOI: 10.1016/j.jhep.2021.02.036] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 02/28/2021] [Indexed: 12/23/2022]

Liu L, Huang H, Li Y, Zhang R, Wei Y, Wu W. Severe Encephalatrophy and Related Disorders From Long-Term Ketamine Abuse: A Case Report and Literature Review. Front Psychiatry 2021;12:707326. [PMID: 34658951 PMCID: PMC8519172 DOI: 10.3389/fpsyt.2021.707326] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Accepted: 09/07/2021] [Indexed: 12/02/2022] Open

Lee A, Wein AN, Doyle MBM, Chapman WC. Liver transplantation for post-COVID-19 sclerosing cholangitis. BMJ Case Rep 2021;14:14/8/e244168. [PMID: 34446515 PMCID: PMC8395362 DOI: 10.1136/bcr-2021-244168] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open

Levy E, Stintzi A, Cohen A, Desjardins Y, Marette A, Spahis S. Critical appraisal of the mechanisms of gastrointestinal and hepatobiliary infection by COVID-19. Am J Physiol Gastrointest Liver Physiol 2021;321:G99-G112. [PMID: 34009033 PMCID: PMC8289353 DOI: 10.1152/ajpgi.00106.2021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]

Abstract

COVID-19 represents a novel infectious disease induced by SARS-CoV-2. It has to date affected 24,240,000 individuals and killed 2,735,805 people worldwide. The highly infectious virus attacks mainly the lung, causing fever, cough, and fatigue in symptomatic patients, but also pneumonia in severe cases. However, growing evidence highlights SARS-CoV-2-mediated extrarespiratory manifestations, namely, gastrointestinal (GI) and hepatic complications. The detection of 1) the virus in the GI system (duodenum, colon, rectum, anal region, and feces); 2) the high expression of additional candidate coreceptors/auxiliary proteins to facilitate the virus entry; 3) the abundant viral angiotensin-converting enzyme 2 receptor; 4) the substantial expression of host transmembrane serine protease 2, necessary to induce virus-cell fusion; 5) the viral replication in the intestinal epithelial cells; and 6) the primarily GI disorders in the absence of respiratory symptoms lead to increased awareness of the risk of disease transmission via the fecal-oral route. The objectives of this review are to provide a brief update of COVID-19 pathogenesis and prevalence, present a critical overview of its GI and liver complications that affect clinical COVID-19 outcomes, clarify associated mechanisms (notably microbiota-related), define whether gut/liver disorders occur more frequently among critically ill patients with COVID-19, determine the impact of COVID-19 on preexisting gut/liver complications and vice versa, and discuss the available strategies for prevention and treatment to improve prognosis of the patients. The novel SARS-CoV-2 can cause gastrointestinal and hepatobiliary manifestations. Metagenomics studies of virobiota in response to SARS-CoV-2 infection are necessary to highlight the contribution of bacterial microflora to COVID-19 phenotype, which is crucial for developing biomarkers and therapeutics.

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de Tymowski C, Dépret F, Dudoignon E, Legrand M, Mallet V. Ketamine-induced cholangiopathy in ARDS patients. Intensive Care Med 2021;47:1173-1174. [PMID: 34313797 PMCID: PMC8315088 DOI: 10.1007/s00134-021-06482-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/14/2021] [Indexed: 12/19/2022]

Affiliation(s)

Christian de Tymowski Department of Anesthesiology and Critical Care and Burn Unit, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier St-Louis-Lariboisière, Paris, France.,University de Paris, Paris, France.,Centre de Recherche sur l'Inflammation (CRI), INSERM U1149, Paris, France.,Laboratoire d'Excellence (Labex) Inflammex, ComUE Sorbonne Paris Cité, Paris, France
François Dépret Department of Anesthesiology and Critical Care and Burn Unit, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier St-Louis-Lariboisière, Paris, France. .,University de Paris, Paris, France. .,Institut National de La Santé Et de La Recherche Médicale (INSERM), UMR INSERM 942, Lariboisière Hospital University Paris Diderot, 75475, Paris, France. .,F-CRIN INI-CRCT Network, Nancy, France.
Emmanuel Dudoignon Department of Anesthesiology and Critical Care and Burn Unit, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier St-Louis-Lariboisière, Paris, France.,University de Paris, Paris, France.,Institut National de La Santé Et de La Recherche Médicale (INSERM), UMR INSERM 942, Lariboisière Hospital University Paris Diderot, 75475, Paris, France
Matthieu Legrand Institut National de La Santé Et de La Recherche Médicale (INSERM), UMR INSERM 942, Lariboisière Hospital University Paris Diderot, 75475, Paris, France.,F-CRIN INI-CRCT Network, Nancy, France.,Department of Critical Care and Peri Operative Medicine, University of California, San Francisco, USA
Vincent Mallet Department of Anesthesiology and Critical Care and Burn Unit, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier St-Louis-Lariboisière, Paris, France.,University de Paris, Paris, France.,AP-HP Centre, Groupe Hospitalier Cochin Port Royal, DMU Cancérologie Et Spécialités Médico-Chirurgicales, Service d'Hépatologie, Université de Paris, Paris, France

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Ketamine. REACTIONS WEEKLY 2021. [PMCID: PMC8160405 DOI: 10.1007/s40278-021-96572-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]

Mallet M, Allaire M, Thabut D, Rudler M. Liver damage associated with Covid-19: A direct causality is difficult to establish. JOURNAL OF LIVER TRANSPLANTATION 2021;2:100011. [PMID: 38620765 PMCID: PMC8108473 DOI: 10.1016/j.liver.2021.100011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 05/05/2021] [Indexed: 11/24/2022] Open