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Mahmoud S, Sarkar A, AlMahmoud L, Alladaboina S, Syed LF, Yaghmour M, Elmoh S, AlShebani M, Aly K, Al-Ansari H, Al-Mohamedi M, Yagan L, Zakaria D. Solid Organ Transplants Caused by COVID-19 Infection and the Outcome of Transplantation Post-COVID-19: A Systematic Review. Biomedicines 2025; 13:428. [PMID: 40002841 PMCID: PMC11852956 DOI: 10.3390/biomedicines13020428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Revised: 01/22/2025] [Accepted: 01/27/2025] [Indexed: 02/27/2025] Open
Abstract
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has imposed several medical and economic challenges since its onset in 2019. This is due to its ability to target the respiratory system as well as other organs, resulting in significant impacts and necessitating organ transplants. Our goal is to compile information from the existing literature to investigate how COVID-19 affects outcomes following organ transplantation. A comprehensive literature search was conducted to target studies reporting post-COVID-19 complications. We included 45 studies reporting data related to solid organ transplants, where either the recipient, organ, or donor was affected by SARS-CoV-2. The majority of the included studies concluded that organ transplantation following COVID-19 infection could be performed safely and with similar outcomes to non-COVID-19 patients, regardless of whether the organ, donor, or recipient was affected by COVID-19. No deviation from standard immunosuppression regimens or surgical protocols was necessary either, further re-assuring the feasibility of these transplants as viable treatment options. This applies to organ transplants involving the lungs, kidneys, liver, or heart. However, there was a limited number of studies in some areas, which warrants the need for additional research in order to reach more concrete conclusions pertaining to COVID-19's effect on organ transplants.
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Affiliation(s)
- Shadi Mahmoud
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
| | - Aparajita Sarkar
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
| | - Latifa AlMahmoud
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
| | - Sushanth Alladaboina
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
| | - Leena F. Syed
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
| | - Mohammad Yaghmour
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
| | - Safaa Elmoh
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
| | - Meera AlShebani
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
| | - Kareem Aly
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
| | - Haya Al-Ansari
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
| | - Mohammed Al-Mohamedi
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
| | - Lina Yagan
- Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Dalia Zakaria
- Department of Pre-Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
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Schneeweiss-Gleixner M, Krenn K, Petter M, Haselwanter P, Kraft F, Adam L, Semmler G, Hartl L, Halilbasic E, Buchtele N, Krall C, Staudinger T, Zauner C, Trauner M, Stättermayer AF. Presence of cholestasis and its impact on survival in SARS-CoV-2 associated acute respiratory distress syndrome. Sci Rep 2024; 14:23377. [PMID: 39379494 PMCID: PMC11461911 DOI: 10.1038/s41598-024-73948-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 09/23/2024] [Indexed: 10/10/2024] Open
Abstract
Data on cholestasis and biliary injury in patients with COVID-19 are scarce. The primary aim of this study was to evaluate the prevalence of cholestasis and factors associated with its development and outcome in critically ill patients with COVID-19 associated acute respiratory distress syndrome (ARDS). In this retrospective exploratory study, COVID-19 patients with ARDS admitted to an intensive care unit (ICU) at the Medical University of Vienna were evaluated for the development of cholestasis defined as an alkaline phosphatase level of 1.67x upper limit of normal for at least three consecutive days. Simple and multiple logistic regression analysis was used to evaluate parameters associated with development of cholestasis and survival. Of 225 included patients 119 (53%) developed cholestasis during ICU stay. Patients with cholestasis had higher peak levels of alkaline phosphatase, gamma-glutamyl transferase, bilirubin and inflammation parameters. Factors independently associated with cholestasis were extracorporeal membrane oxygenation support, ketamine use, high levels of inflammation parameters and disease severity. Presence of cholestasis and peak ALP levels were independently associated with worse ICU and 6-month survival. Development of cholestasis is a common complication in critically ill COVID-19 patients and represents a negative prognostic marker for survival. It is associated with disease severity and specific treatment modalities of intensive care.
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Affiliation(s)
- Mathias Schneeweiss-Gleixner
- Department of Medicine III, Division of Gastroenterology and Hepatology with Intensive Care Unit 13h1, Medical University of Vienna, Vienna, Austria
| | - Katharina Krenn
- Department of Anesthesia, General Intensive Care and Pain Medicine, Medical University of Vienna, Vienna, Austria
| | - Mathias Petter
- Department of Medicine III, Division of Gastroenterology and Hepatology with Intensive Care Unit 13h1, Medical University of Vienna, Vienna, Austria
| | - Patrick Haselwanter
- Department of Medicine III, Division of Gastroenterology and Hepatology with Intensive Care Unit 13h1, Medical University of Vienna, Vienna, Austria
| | - Felix Kraft
- Department of Anesthesia, General Intensive Care and Pain Medicine, Medical University of Vienna, Vienna, Austria
| | - Lukas Adam
- Department of Anesthesia, General Intensive Care and Pain Medicine, Medical University of Vienna, Vienna, Austria
| | - Georg Semmler
- Department of Medicine III, Division of Gastroenterology and Hepatology with Intensive Care Unit 13h1, Medical University of Vienna, Vienna, Austria
| | - Lukas Hartl
- Department of Medicine III, Division of Gastroenterology and Hepatology with Intensive Care Unit 13h1, Medical University of Vienna, Vienna, Austria
| | - Emina Halilbasic
- Department of Medicine III, Division of Gastroenterology and Hepatology with Intensive Care Unit 13h1, Medical University of Vienna, Vienna, Austria
| | - Nina Buchtele
- Department of Medicine I, Intensive Care Unit 13i2, Medical University of Vienna, Vienna, Austria
| | - Christoph Krall
- Department of Medical Statistics, Medical University of Vienna, Vienna, Austria
| | - Thomas Staudinger
- Department of Medicine I, Intensive Care Unit 13i2, Medical University of Vienna, Vienna, Austria
| | - Christian Zauner
- Department of Medicine III, Division of Gastroenterology and Hepatology with Intensive Care Unit 13h1, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Department of Medicine III, Division of Gastroenterology and Hepatology with Intensive Care Unit 13h1, Medical University of Vienna, Vienna, Austria.
| | - Albert Friedrich Stättermayer
- Department of Medicine III, Division of Gastroenterology and Hepatology with Intensive Care Unit 13h1, Medical University of Vienna, Vienna, Austria.
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Pogorelova M, Kusztos V. Secondary Sclerosing Cholangitis (SSC): An Underrecognized Complication of Severe COVID-19 Pneumonitis. Cureus 2024; 16:e70003. [PMID: 39445269 PMCID: PMC11498318 DOI: 10.7759/cureus.70003] [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] [Accepted: 09/22/2024] [Indexed: 10/25/2024] Open
Abstract
COVID-19-secondary sclerosing cholangitis (COVID-SSC) is a distinct subset of secondary sclerosing cholangitis in critically ill patients (SSC-CIP) that presents after COVID-19 infection with alkaline phosphatase predominant elevation of liver enzymes. COVID-SSC typically presents within three months of COVID-19 diagnosis and most commonly occurs following severe COVID-19 infection. COVID-SSC can have different clinical degrees of severity, ranging from clinically latent, as shown in this case report, to severely symptomatic, requiring a liver transplant or leading to patient death. We present a case of COVID-SSC that presented in an asymptomatic patient months after severe COVID pneumonitis requiring prolonged intubation who was initially misdiagnosed with autoimmune hepatitis and found to have early cirrhosis at the time of diagnosis. The case presented was initially clinically silent and overlooked for months. In the aftermath of severe COVID-19 infection, COVID-SSC should be included in the differential diagnosis of unclear cholestasis, and general practitioners should have a high index of suspicion when encountering disproportionate elevation of alkaline phosphatase in patients with a history of COVID-19, in particular, those requiring intensive care unit (ICU) level cares.
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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
Abstract
Cholangiopathy has been described in survivors of severe COVID-19, presenting significant clinical parallels to the pre-pandemic condition of secondary sclerosing cholangitis in critically ill patients (SSC-CIP). We aimed to examine the liver histopathology of individuals with persistent cholestasis after severe COVID-19. METHODS We subjected post-COVID-19 cholestasis liver samples to routine staining techniques and cytokeratin 7 immunostaining and semi-quantitatively analyzed the portal and parenchymal changes. RESULTS All ten patients, five men, had a median age of 56, an interquartile range (IQR) of 51-60, and required intensive care unit and mechanical ventilation. The median and IQR liver enzyme concentrations proximal to biopsy were in IU/L: ALP 645 (390-1256); GGT 925 (664-2169); ALT 100 (86-113); AST 87 (68-106); and bilirubin 4 (1-9) mg/dL. Imaging revealed intrahepatic bile duct anomalies and biliary casts. We performed biopsies at a median of 203 (150-249) days after molecular confirmation of infection. We found portal and periportal fibrosis, moderate-to-severe ductular proliferation, and bile duct dystrophy in all patients, while we observed hepatocyte biliary metaplasia in all tested cases. We observed mild-to-severe parenchymal cholestasis and bile plugs in nine and six cases. We also observed mild swelling of the arteriolar endothelial cells in five patients. We observed a thrombus in a small portal vein branch and mild periductal fibrosis in one case each. One patient developed multiple small biliary infarctions. We did not observe ductopenia in any patient. CONCLUSIONS The alterations were like those observed in SSC-CIP; however, pronounced swelling of endothelial cells, necrosis of the vessel walls, and thrombosis in small vessels were notable.
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Affiliation(s)
- Valéria F. A. Borges
- Postgraduate Program in Medicine and Health, Federal University of Bahia, Salvador 40026-010, Brazil;
| | - Helma P. Cotrim
- School of Medicine of Bahia, Federal University of Bahia, Salvador 40026-010, Brazil; (A.R.C.F.A.); (L.A.R.F.)
| | | | | | - Francisco G. C. Penna
- Department of Internal Medicine, School of Medicine, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil;
| | | | | | - Luiz A. R. Freitas
- School of Medicine of Bahia, Federal University of Bahia, Salvador 40026-010, Brazil; (A.R.C.F.A.); (L.A.R.F.)
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FioCruz), Salvador 402596-710, Brazil
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Fischer AK, Stippel D, Canbay A, Nierhoff D, Thomas M, Best J, Büttner R, Drebber U. COVID-19-associated secondary sclerosing cholangitis with liver transplantation. Virchows Arch 2024; 485:371-377. [PMID: 38526652 PMCID: PMC11329547 DOI: 10.1007/s00428-024-03753-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 01/22/2024] [Accepted: 01/27/2024] [Indexed: 03/27/2024]
Abstract
We report on two cases of orthotopic liver transplantation (OLTX) due to SARS-Cov2-associated secondary sclerosing cholangitis (SSC) following long-term artificial respiration and extra-corporal membrane oxygenation in intensive care. Under these conditions, SSC is a rapidly progredient biliary disease featuring degenerative cholangiopathy, loss of bile ducts, ductular and parenchymal cholestasis, biliary fibrosis, and finally cirrhosis. Reduced perfusion and oxygenation of the peribiliary plexus, severe concurrent infections, and secondary medico-toxic effects appear to play a crucial role in the pathogenesis of the disease. A direct cytopathic effect of SARS-Cov2 on endothelial cells followed by thrombosis and fibrosing obliteration in all parts of the vascular bed of the liver may enhance the virus-associated liver disease and particularly SSC.
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Affiliation(s)
- Anne Kristin Fischer
- Institute of Pathology, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
| | - Dirk Stippel
- Department of Surgery, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Ali Canbay
- Department of Internal Medicine, Transplant Medicine, Gastroenterology and Hepatology, University of Bochum, In Der Schornau 23-25 44892, Bochum, Germany
| | - Dirk Nierhoff
- Department of Internal Medicine, Gastroenterology and Hepatology, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Michael Thomas
- Department of Surgery, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Jan Best
- Department of Internal Medicine, Transplant Medicine, Gastroenterology and Hepatology, University of Bochum, In Der Schornau 23-25 44892, Bochum, Germany
| | - Reinhard Büttner
- Institute of Pathology, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Uta Drebber
- Institute of Pathology, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
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Rodriguez-Espada A, Salgado-de la Mora M, Rodriguez-Paniagua BM, Limon-de la Rosa N, Martinez-Gutierrez MI, Pastrana-Brandes S, Navarro-Alvarez N. Histopathological impact of SARS-CoV-2 on the liver: Cellular damage and long-term complications. World J Gastroenterol 2024; 30:2866-2880. [PMID: 38947288 PMCID: PMC11212712 DOI: 10.3748/wjg.v30.i22.2866] [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: 03/08/2024] [Revised: 05/08/2024] [Accepted: 05/24/2024] [Indexed: 06/05/2024] Open
Abstract
Coronavirus disease 2019 (COVID-19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome, multiple organ failure, and death. Despite extensive studies on the pathogenicity of SARS-CoV-2, its impact on the hepatobiliary system remains unclear. While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels, the exact source of this damage is not fully understood. Proposed mechanisms for injury include direct cytotoxicity, collateral damage from inflammation, drug-induced liver injury, and ischemia/hypoxia. However, evidence often relies on blood tests with liver enzyme abnormalities. In this comprehensive review, we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients, drawing from liver biopsies, complete autopsies, and in vitro liver analyses. We present evidence of the direct impact of SARS-CoV-2 on the liver, substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes, including mitochondrial swelling, endoplasmic reticulum dilatation, and hepatocyte apoptosis. Additionally, we describe the diverse liver pathology observed during COVID-19 infection, encompassing necrosis, steatosis, cholestasis, and lobular inflammation. We also discuss the emergence of long-term complications, notably COVID-19-related secondary sclerosing cholangitis. Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.
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Affiliation(s)
- Alfonso Rodriguez-Espada
- Department of Molecular Biology, Universidad Panamericana School of Medicine, Campus México, Mexico 03920, Mexico
| | - Moises Salgado-de la Mora
- Department of Internal Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico 14080, Mexico
| | | | - Nathaly Limon-de la Rosa
- Department of Surgery, University of Colorado Anschutz Medical Campus, Denver, CO 80045, United States
| | | | - Santiago Pastrana-Brandes
- Department of Molecular Biology, Universidad Panamericana School of Medicine, Campus México, Mexico 03920, Mexico
| | - Nalu Navarro-Alvarez
- Department of Molecular Biology, Universidad Panamericana School of Medicine, Campus México, Mexico 03920, Mexico
- Department of Surgery, University of Colorado Anschutz Medical Campus, Denver, CO 80045, United States
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico 14080, Mexico
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7
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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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Werner CR, Fusco S, Kienzle K, Döbele S, Artzner K, Malek NP, Wichmann D, Göpel S. Incidence of Secondary Sclerosing Cholangitis in Hospitalized Long COVID-19 Patients: A Retrospective Single Center Study. Diagnostics (Basel) 2024; 14:745. [PMID: 38611659 PMCID: PMC11011916 DOI: 10.3390/diagnostics14070745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 03/23/2024] [Accepted: 03/29/2024] [Indexed: 04/14/2024] Open
Abstract
BACKGROUND SARS-CoV-2 infection and associated COVID-19 disease can lead to critical illness with a risk of developing a multiple organ failure. Subsequently, this may lead to various pathological sequelae, such as secondary sclerosing cholangitis after surviving COVID-19 (SSC-COVID). OBJECTIVE The aim is to retrospectively analyze a cohort of hospitalized patients with first-wave (February 2020-June 2020) SARS-CoV-2 infection and persisting unclear cholangiopathy to determine the incidence of SSC-COVID and its risk factors. RESULTS A total of 249 patients were hospitalized at the university hospital in Tübingen, Germany, with SARS-CoV-2 infection during the first wave of the pandemic. Of these, 35.3% (88/249) required intensive care treatment; 16.5% (41/249) of them died due to the complications of COVID-19; 30.8% (64/208) of surviving patients could be followed up und were retrospectively analyzed at our center. The incidence of confirmed SSC-COVID was 7.8% (5/64). All SSC-COVID patients had an ICU stay >20 days, for invasive ventilation, positioning treatment, vasopressor treatment, but possible risk factors for SSC were not significant due to the small number of patients. CONCLUSIONS SSC-COVID is an emerging disease in post-COVID patients with a high incidence in our single-center cohort. SSC-COVID should be considered as a differential diagnosis, if unclear cholangiopathy or cholestasis persists after SARS-CoV-2 infection.
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Affiliation(s)
- Christoph R. Werner
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectious Diseases and Geriatrics, University Hospital Tübingen, Otfried-Müller-Strasse 10, 72076 Tübingen, Germany; (C.R.W.); (K.A.); (N.P.M.); (D.W.); (S.G.)
| | - Stefano Fusco
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectious Diseases and Geriatrics, University Hospital Tübingen, Otfried-Müller-Strasse 10, 72076 Tübingen, Germany; (C.R.W.); (K.A.); (N.P.M.); (D.W.); (S.G.)
| | - Katharina Kienzle
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectious Diseases and Geriatrics, University Hospital Tübingen, Otfried-Müller-Strasse 10, 72076 Tübingen, Germany; (C.R.W.); (K.A.); (N.P.M.); (D.W.); (S.G.)
| | - Stefanie Döbele
- Institute for Medical Microbiology and Hygiene, University Hospital Tübingen, 72076 Tübingen, Germany;
| | - Kerstin Artzner
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectious Diseases and Geriatrics, University Hospital Tübingen, Otfried-Müller-Strasse 10, 72076 Tübingen, Germany; (C.R.W.); (K.A.); (N.P.M.); (D.W.); (S.G.)
| | - Nisar P. Malek
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectious Diseases and Geriatrics, University Hospital Tübingen, Otfried-Müller-Strasse 10, 72076 Tübingen, Germany; (C.R.W.); (K.A.); (N.P.M.); (D.W.); (S.G.)
| | - Dörte Wichmann
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectious Diseases and Geriatrics, University Hospital Tübingen, Otfried-Müller-Strasse 10, 72076 Tübingen, Germany; (C.R.W.); (K.A.); (N.P.M.); (D.W.); (S.G.)
| | - Siri Göpel
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectious Diseases and Geriatrics, University Hospital Tübingen, Otfried-Müller-Strasse 10, 72076 Tübingen, Germany; (C.R.W.); (K.A.); (N.P.M.); (D.W.); (S.G.)
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9
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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: 11] [Impact Index Per Article: 5.5] [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]
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.
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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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10
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Sambommatsu Y, Mouch C, Kulkarni AV, Bruno DA, Eslami M, Imai D, Lee SD, Khan AA, Sharma A, Saeed M, Cotterell AH, Levy MF, Morales MK, Montenovo MI, Rao PN, Reddy R, Menon B, Kumaran V. Liver transplantation for post-COVID-19 cholangiopathy: A case series. Clin Transplant 2023; 37:e15141. [PMID: 37755152 DOI: 10.1111/ctr.15141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 09/17/2023] [Indexed: 09/28/2023]
Abstract
BACKGROUND Post-COVID-19 cholangiopathy is an emerging cholestatic liver disease observed in patients recovering from severe COVID-19 infection. Its prognosis is poor, necessitating liver transplantation in some cases. This study aimed to investigate the outcomes of liver transplantation for post-COVID-19 cholangiopathy. METHODS Seven patients who underwent liver transplantation for post-COVID-19 cholangiopathy at three institutions between 2020 and 2022 were included in this retrospective multi-center case series. RESULTS At the time of initial COVID-19 infection, all patients developed acute respiratory distress syndrome, and six patients (86%) required ICU admission. Median time intervals from the initial COVID-19 diagnosis to the diagnosis of post-COVID-19 cholangiopathy and liver transplantation were 4 and 12 months, respectively. Four patients underwent living donor liver transplantation, and three patients underwent deceased donor liver transplantation. The median MELD score was 22 (range, 10-38). No significant intraoperative complications were observed. The median ICU and hospital stays were 2.5 and 12.5 days, respectively. One patient died due to respiratory failure 5 months after liver transplantation. Currently, the patient and graft survival rate is 86% at a median follow-up of 11 months. CONCLUSIONS Liver transplantation is a viable option for patients with post-COVID-19 cholangiopathy with acceptable outcome. Timely identification of this disease and appropriate management, including evaluation for liver transplantation, are essential.
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Affiliation(s)
- Yuzuru Sambommatsu
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Charles Mouch
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Anand V Kulkarni
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
| | - David A Bruno
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Mehdi Eslami
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Daisuke Imai
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Seung Duk Lee
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Aamir A Khan
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Amit Sharma
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Muhammad Saeed
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Adrian H Cotterell
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Marlon F Levy
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Megan K Morales
- Department of Internal Medicine, Division of Infectious Disease, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Martin I Montenovo
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Padaki N Rao
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Raghuram Reddy
- Department of Liver Transplantation and Hepatobiliary Surgery, Asian Institute of Gastroenterology, Hyderabad, India
| | - Balachandran Menon
- Department of Liver Transplantation and Hepatobiliary Surgery, Asian Institute of Gastroenterology, Hyderabad, India
| | - Vinay Kumaran
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
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11
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Paniskaki K, Goretzki S, Anft M, Konik MJ, Meister TL, Pfaender S, Lechtenberg K, Vogl M, Dogan B, Dolff S, Westhoff TH, Rohn H, Felderhoff-Mueser U, Stervbo U, Witzke O, Dohna-Schwake C, Babel N. Increased SARS-CoV-2 reactive low avidity T cells producing inflammatory cytokines in pediatric post-acute COVID-19 sequelae (PASC). Pediatr Allergy Immunol 2023; 34:e14060. [PMID: 38146118 DOI: 10.1111/pai.14060] [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: 07/22/2023] [Revised: 11/13/2023] [Accepted: 11/29/2023] [Indexed: 12/27/2023]
Abstract
BACKGROUND A proportion of the convalescent SARS-CoV-2 pediatric population presents nonspecific symptoms, mental health problems, and a reduction in quality of life similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID-19 symptomatic. However, data regarding its clinical manifestation and immune mechanisms are currently scarce. METHODS In this study, we perform a comprehensive clinical and immunological profiling of 17 convalescent COVID-19 children with post-acute COVID-19 sequelae (PASC) manifestation and 13 convalescent children without PASC manifestation. A detailed medical history, blood and instrumental tests, and physical examination were obtained from all patients. SARS-CoV-2 reactive T-cell response was analyzed via multiparametric flow cytometry and the humoral immunity was addressed via pseudovirus neutralization and ELISA assay. RESULTS The most common PASC symptoms were shortness of breath/exercise intolerance, paresthesia, smell/taste disturbance, chest pain, dyspnea, headache, and lack of concentration. Blood count and clinical chemistry showed no statistical differences among the study groups. We detected higher frequencies of spike (S) reactive CD4+ and CD8+ T cells among the PASC study group, characterized by TNFα and IFNγ production and low functional avidity. CRP levels are positively correlated with IFNγ producing reactive CD8+ T cells. CONCLUSIONS Our data might indicate a possible involvement of a persistent cellular inflammatory response triggered by SARS-CoV-2 in the development of the observed sequelae in pediatric PASC. These results may have implications on future therapeutic and prevention strategies.
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Affiliation(s)
- Krystallenia Paniskaki
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Bochum, Germany
| | - Sarah Goretzki
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Department of Pediatrics I, Children's Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Moritz Anft
- Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Bochum, Germany
| | - Margarethe J Konik
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Toni L Meister
- Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany
| | - Stephanie Pfaender
- Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany
| | - Klara Lechtenberg
- Department of Pediatrics I, Children's Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Melanie Vogl
- Department of Pediatrics III, Pediatric Pulmonology and Sleep Medicine, Children's Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Burcin Dogan
- Department of Pediatrics I, Children's Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Sebastian Dolff
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Timm H Westhoff
- Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany
| | - Hana Rohn
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Ursula Felderhoff-Mueser
- Department of Pediatrics I, Children's Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Center for Translational Neuro- and Behavioral Sciences C-TNBS, University of Duisburg-Essen, Essen, Germany
| | - Ulrik Stervbo
- Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Bochum, Germany
| | - Oliver Witzke
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Christian Dohna-Schwake
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Department of Pediatrics I, Children's Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Center for Translational Neuro- and Behavioral Sciences C-TNBS, University of Duisburg-Essen, Essen, Germany
| | - Nina Babel
- Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Bochum, Germany
- Berlin Institute of Health at Charité - University Clinic Berlin, BIH Center for Regenerative Therapies (BCRT) Berlin, Berlin, Germany
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12
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Bazerbachi F, Servin-Abad LA, Nassani N, Mönkemüller K. Endosonographic and ERCP findings in COVID-19 critical illness cholangiopathy. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2023; 115:648-649. [PMID: 36205332 DOI: 10.17235/reed.2022.9218/2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
A 56-year-old female developed deep jaundice months after struggling with critical illness due to COVID-19, requiring hemodialysis and tracheostomy. Lab tests included alkaline phosphatase 1,574 U/l, total bilirubin 11 mg/dl, alanine transaminase (ALT) 88 U/l and aspartate aminotransferase (AST) 101 U/l. Baseline liver tests were normal before illness. Anti-nuclear antibodies (ANA), IgG4 level and viral hepatitis were negaCritical illness cholangiopathy resulted in secondary sclerosing cholangitis. In this case, it is unclear whether the patient suffered these changes as a direct cause of COVID-19 or as a result of critical illness cholangiopathy. The overall prognosis is guarded given its progressive nature and likely need for liver transplantation.tive.
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Affiliation(s)
| | | | | | - Klaus Mönkemüller
- Gastroenterology, Ameos Klinikum University Teaching Hospital, Germany
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13
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John N, Ibrahim B, Ebaid M, Saab S. Outcomes in Patients with Liver Dysfunction Post SARS-CoV-2 Infection: What Should We Measure? Hepat Med 2023; 15:185-193. [PMID: 37850074 PMCID: PMC10578169 DOI: 10.2147/hmer.s371507] [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: 06/28/2023] [Accepted: 09/28/2023] [Indexed: 10/19/2023] Open
Abstract
Aim Since 2019, the COVID-19 pandemic wreaked havoc all over the world. Early in the course of the pandemic, multiple hepatic manifestations of COVID-19 were noted. We aim to categorize hepatic dysfunction and its outcome in COVID-19 infection. Methods This is a review article based on a literature search in PubMed and Medline databases for articles detailing short-term and long-term outcomes of COVID-19 related liver dysfunction. Results The most common hepatic manifestation of COVID-19 was aspartate amino transferase (AST) predominant transaminase elevation. Transaminases improve once the COVID-19 infection resolves. In addition, COVID-19 cholangiopathy, autoimmune hepatitis associated COVID-19, and splanchnic venous thrombosis triggered by COVID-19 are other manifestations. Patients with preexisting liver disease, especially those with cirrhosis, have poor prognosis with COVID-19 infections compared to the general population. Elevations in liver tests were associated with severe COVID-19 infections. Patients with chronic liver disease have a higher risk of morbidity and mortality from COVID-19 infection. Among patients with chronic liver disease, decompensated liver cirrhosis, hepatocellular carcinoma and alcohol-associated liver disease were associated with an increased risk of severity and mortality from COVID-19 infection. Interactions between antiviral therapy for COVID-19 and hepatitis B/hepatitis C medications must be considered in patients with chronic viral hepatitis and COVID-19 infection. COVID-19 vaccination-related hepatic dysfunction has been reported. Conclusion COVID-19 is here to stay. Hepatic dysfunction in COVID-19 signals severe COVID-19 infections. Patients with chronic liver disease have higher mortality from COVID-19 than general population. It is important to remember the lessons learned throughout the covid pandemic to take care of patients with COVID-19 now and in the future. Further studies are needed to document long-term outcomes in patients with COVID-19 who developed hepatic dysfunction.
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Affiliation(s)
- Nimy John
- Department of Medicine, University of California, Los Angeles, CA, USA
| | - Brittney Ibrahim
- Department of Surgery, University of California, Los Angeles, CA, USA
| | - Mark Ebaid
- Department of Surgery, University of California, Los Angeles, CA, USA
| | - Sammy Saab
- Department of Medicine, University of California, Los Angeles, CA, USA
- Department of Surgery, University of California, Los Angeles, CA, USA
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14
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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
Abstract
The COVID-19 pandemic has had a profound impact on global health, necessitating a comprehensive understanding of its diverse manifestations. Cholangiopathy, a condition characterized by biliary dysfunction, has emerged as a significant complication in COVID-19 patients. In this review, we report the epidemiology of COVID-19, describe the hepatotropism of SARS-CoV-2, and present the histopathology of acute liver injury (ALI) in COVID-19. Additionally, we explore the relationship between pre-existing chronic liver disease and COVID-19, shedding light on the increased susceptibility of these individuals to develop cholangiopathy. Through an in-depth analysis of cholangiopathy in COVID-19 patients, we elucidate its clinical manifestations, diagnostic criteria, and underlying pathogenesis involving inflammation, immune dysregulation, and vascular changes. Furthermore, we provide a summary of studies investigating post-COVID-19 cholangiopathy, highlighting the long-term effects and potential management strategies for this condition, and discussing opportunities for intervention, including therapeutic targets, diagnostic advancements, supportive care, and future research needs.
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Affiliation(s)
- Joseph K Lim
- Yale Liver Center and Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
| | - Basile Njei
- Yale Liver Center and Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
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15
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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: 3] [Impact Index Per Article: 1.5] [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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Affiliation(s)
| | | | | | - Jonathan Soldera
- Acute Medicine, University of South Wales, Cardiff CF37 1DL, United Kingdom
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16
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Fiel MI, Schiano TD. Systemic Disease and the Liver-Part 1: Systemic Lupus Erythematosus, Celiac Disease, Rheumatoid Arthritis, and COVID-19. Surg Pathol Clin 2023; 16:473-484. [PMID: 37536883 DOI: 10.1016/j.path.2023.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/05/2023]
Abstract
The development of liver dysfunction in patients having various systemic diseases is common and has a broad differential diagnosis, at times being the initial manifestation of the disorder. Liver injury associated with systemic lupus erythematosus is heterogeneous and may present with nonspecific histology. Differentiating autoimmune hepatitis from lupus hepatitis is challenging on histologic grounds alone. Other systemic diseases that may present mostly with nonspecific findings are rheumatoid arthritis and celiac disease. More recently COVID-19 cholangiopathy and secondary sclerosing cholangitis have become increasingly recognized as distinct liver conditions. Many patients may also have intrinsic liver disease or may develop drug-induced liver injury from the treatment of the systemic disease. Timely identification of the cause of the liver dysfunction is essential and liver biopsy may help the clinician in diagnosis and management.
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Affiliation(s)
- Maria Isabel Fiel
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY 10029, USA
| | - Thomas D Schiano
- Division of Liver Diseases, Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place-Box 1104, New York, NY 10029, USA.
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17
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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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Affiliation(s)
- Alessandra Bartoli
- Division of Internal Medicine and Metabolism, Department of Internal Medicine, Ospedale Civile di Baggiovara, University of Modena and Reggio Emilia, Modena, Italy
- Post Graduate School of Allergy and Clinical Immunology, Department of Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Carmela Cursaro
- Division of Internal Medicine and Metabolism, Department of Internal Medicine, Ospedale Civile di Baggiovara, University of Modena and Reggio Emilia, Modena, Italy
| | - Hajrie Seferi
- Division of Internal Medicine and Metabolism, Department of Internal Medicine, Ospedale Civile di Baggiovara, University of Modena and Reggio Emilia, Modena, Italy
| | - Pietro Andreone
- Chief of Division of Internal Medicine and metabolism, Department of Internal Medicine, University Hospital of Modena, Modena, Italy
- Chief of Post Graduate School of Allergy and Clinical Immunology, Department of Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy
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18
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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
Abstract
BACKGROUND The recent and still ongoing pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entailed various long-term complications, including post-infectious cholangiopathy.
AIM To identify the available studies concerning post-coronavirus disease 2019 (COVID-19) cholangiopathy.
METHODS An extensive bibliographical search was carried out in PubMed and in Cochrane Library to identify the articles (retrospective and prospective studies, cohort studies, case series and case reports) published between January 1, 2020 and August 22, 2022, using both MeSH terms and free-language keywords: cholangiopathy; COVID-19; post-COVID-19 cholangiopathy; SARS-CoV-2.
RESULTS Thirteen studies fulfilled the inclusion criteria, which included 64 patients suffering from this condition. The patients were male in 82.8% of cases. Liver transplant was executed in 6 patients and scheduled in 7 patients, while 2 patients refused the surgical approach. Therefore in 23.4% of the cases, performing this procedure appeared to be necessary.
CONCLUSION This review has revealed that generally the involvement of the liver in the course of SARS-CoV-2 infection is mild and transient, inducing cholestasis of cholangiocytes but can also be severe enough to cause organ failure in some cases.
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Affiliation(s)
- Maddalena Zippi
- Unit of Gastroenterology and Digestive Endoscopy, Sandro Pertini Hospital, Rome 00157, Italy
| | - Sirio Fiorino
- Unit of Internal Medicine, Maggiore Hospital, Local Health Unit of Bologna, Bologna 40133, Italy
| | - Wandong Hong
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Dario de Biase
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | | | - Alfonso Grottesi
- Unit of General Surgery, Sandro Pertini Hospital, Rome 00157, Italy
| | | | - Pietro Crispino
- Unit of Emergency Medicine, Santa Maria Goretti Hospital, Latina 04100, Italy
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19
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Veerankutty FH, Sengupta K, Vij M, Rammohan A, Jothimani D, Murali A, Rela M. Post-COVID-19 cholangiopathy: Current understanding and management options. World J Gastrointest Surg 2023; 15:788-798. [PMID: 37342848 PMCID: PMC10277943 DOI: 10.4240/wjgs.v15.i5.788] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 02/10/2023] [Accepted: 04/07/2023] [Indexed: 05/26/2023] Open
Abstract
Post-coronavirus disease 2019 (COVID-19) cholangiopathy (PCC) is a rare but life-threatening complication of COVID-19 infection. PCC typically presents when patients recovering from the contagion and manifests as cholestasis in patients with no history of pre-existing liver disease. The pathogenesis of PCC is little understood. Hepatic injury in PCC could be mediated by the predilection of severe acute respiratory syndrome coronavirus 2 for cholangiocytes. Though PCC shows some resemblance to secondary sclerosing cholangitis in critically ill patients, it is considered as a separate and unique entity in the literature. Various treatment options like ursodeoxycholic acid, steroids, plasmapheresis, and endoscopic retrograde cholangiopancreatography guided interventions have been tried but with limited success. We have noticed significant improvement in liver function with antiplatelet therapy in a couple of patients. PCC can progress to end-stage liver disease necessitating liver transplantation. In this article, we discuss the current knowledge of PCC focusing on its pathophysiology, clinical manifestations, and management strategies.
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Affiliation(s)
- Fadl H Veerankutty
- Institute of Liver Disease and Transplantation, Dr. Rela Institute and Research Centre, Chennai 600044, India
| | - Kushan Sengupta
- Institute of Liver Disease and Transplantation, Dr. Rela Institute and Medical Centre, Chennai 600044, India
| | - Mukul Vij
- Department of Pathology, Institute of Liver Disease and Transplantation, Chennai 600044, India
| | - Ashwin Rammohan
- Institute of Liver Disease and Transplantation, Dr. Rela Institute and Medical Centre, Chennai 600044, India
| | - Dinesh Jothimani
- Institute of Liver Disease and Transplantation, Dr. Rela Institute and Medical Centre, Chennai 600044, India
| | | | - Mohamed Rela
- Institute of Liver Disease and Transplantation, Dr. Rela Institute and Medical Centre, Chennai 600044, India
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20
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Liatsos GD. SARS-CoV-2 induced liver injury: Incidence, risk factors, impact on COVID-19 severity and prognosis in different population groups. World J Gastroenterol 2023; 29:2397-2432. [PMID: 37179584 PMCID: PMC10167898 DOI: 10.3748/wjg.v29.i16.2397] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 02/17/2023] [Accepted: 04/07/2023] [Indexed: 04/24/2023] Open
Abstract
Liver is unlikely the key organ driving mortality in coronavirus disease 2019 (COVID-19) however, liver function tests (LFTs) abnormalities are widely observed mostly in moderate and severe cases. According to this review, the overall prevalence of abnormal LFTs in COVID-19 patients ranges from 2.5% to 96.8% worldwide. The geographical variability in the prevalence of underlying diseases is the determinant for the observed discrepancies between East and West. Multifactorial mechanisms are implicated in COVID-19-induced liver injury. Among them, hypercytokinemia with "bystander hepatitis", cytokine storm syndrome with subsequent oxidative stress and endotheliopathy, hypercoagulable state and immuno-thromboinflammation are the most determinant mechanisms leading to tissue injury. Liver hypoxia may also contribute under specific conditions, while direct hepatocyte injury is an emerging mechanism. Except for initially observed severe acute respiratory distress syndrome corona virus-2 (SARS-CoV-2) tropism for cholangiocytes, more recent cumulative data show SARS-CoV-2 virions within hepatocytes and sinusoidal endothelial cells using electron microscopy (EM). The best evidence for hepatocellular invasion by the virus is the identification of replicating SARS-CoV-2 RNA, S protein RNA and viral nucleocapsid protein within hepatocytes using in-situ hybridization and immunostaining with observed intrahepatic presence of SARS-CoV-2 by EM and by in-situ hybridization. New data mostly derived from imaging findings indicate possible long-term sequelae for the liver months after recovery, suggesting a post-COVID-19 persistent live injury.
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Affiliation(s)
- George D Liatsos
- Department of Internal Medicine, Hippokration General Hospital, Athens 11527, Attiki, Greece
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21
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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
Abstract
Since its emergence in 2019, it has become apparent that coronavirus 2019 (COVID-19) infection can result in multi systemic involvement. In addition to pulmonary symptoms, hepatobiliary involvement has been widely reported. Extent of hepatic involvement ranges from minor elevation in liver function tests (LFTs) to significant hepatocellular or cholestatic injury. In majority of cases, resolution of hepatic injury or improvement in LFTs is noted as patients recover from COVID-19 infection. However, severe biliary tract injury progressing to liver failure has been reported in patients requiring prolonged intensive care unit stay or mechanical ventilation. Due to the timing of its presentation, this form of progressive cholestatic injury has been referred to as COVID-19 cholangiopathy or post-COVID-19 cholangiopathy, and can result in devastating consequences for patients. COVID-19 cholangiopathy is recognized by dramatic elevation in serum alkaline phosphatase and bilirubin and radiologic evidence of bile duct injury. Cholangiopathy in COVID-19 occurs weeks to months after the initial infection and during the recovery phase. Imaging findings and pathology often resemble bile duct injury associated with primary or secondary sclerosing cholangitis. Etiology of COVID-19 cholangiopathy is unclear. Several mechanisms have been proposed, including direct cholangiocyte injury, vascular compromise, and cytokine release syndromes. This review summarizes existing data on COVID-19 cholangiopathy, including reported cases in the literature, proposed pathophysiology, diagnostic testing, and long-term implications.
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Affiliation(s)
- Sujani Yadlapati
- Department of Gastroenterology, Cooper University Hospital, Cooper Medical School of Rowan University, Camden, NJ 08103, United States
| | - Simone A. Jarrett
- Department of Internal Medicine, Einstein Medical Center, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19140, United States
| | - Daniel Baik
- Department of Gastroenterology, Cooper University Hospital, Cooper Medical School of Rowan University, Camden, NJ 08103, United States
| | - Adib Chaaya
- Department of Gastroenterology, Cooper University Hospital, Cooper Medical School of Rowan University, Camden, NJ 08103, United States
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22
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Mansour S, Marjieh R, Kluger Y, Gilshtein H, Khuri S. Post-COVID-19 Cholangiopathy: A Recent Indication for Liver Transplantation. J Clin Med Res 2023; 15:250-254. [PMID: 37187714 PMCID: PMC10181353 DOI: 10.14740/jocmr4914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 04/04/2023] [Indexed: 05/15/2023] Open
Affiliation(s)
- Subhi Mansour
- Department of General Surgery, Rambam Medical Center, Haifa, Israel
| | - Rozan Marjieh
- Department of General Surgery, Rambam Medical Center, Haifa, Israel
| | - Yoram Kluger
- Department of General Surgery, Rambam Medical Center, Haifa, Israel
- HPB and Surgical Oncology Unit, Rambam Medical Center, Haifa, Israel
| | - Hayim Gilshtein
- Department of General Surgery, Rambam Medical Center, Haifa, Israel
- Colorectal Surgery Unit, Rambam Medical Center, Haifa, Israel
| | - Safi Khuri
- Department of General Surgery, Rambam Medical Center, Haifa, Israel
- HPB and Surgical Oncology Unit, Rambam Medical Center, Haifa, Israel
- Corresponding Author: Safi Khuri, Department of General Surgery, Rambam Medical Center, Haifa, Israel.
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23
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Seifert M, Kneiseler G, Dechene A. Secondary Sclerosing Cholangitis due to Severe COVID-19: An Emerging Disease Entity? Digestion 2023:1-7. [PMID: 36889285 PMCID: PMC10025365 DOI: 10.1159/000528689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 12/12/2022] [Indexed: 03/10/2023]
Abstract
INTRODUCTION Coronavirus disease 2019 (COVID-19) can lead to many extrapulmonary manifestations. In this case series, we report on 7 patients developing secondary sclerosing cholangitis (SSC) after severe COVID-19 with intensive care treatment. METHODS Between March 2020 and November 2021, 544 patient cases with cholangitis treated at a German tertiary care centre were screened for SSC. Patients found to be suffering from SSC were assigned to COVID-19 group if SSC presented after a severe course of COVID-19 and to non-COVID-19 group if not. Peak liver parameters as well as intensive care treatment factors and data generated from liver elastography were compared between both groups. RESULTS We identified 7 patients who developed SSC after a severe course of COVID-19. In the same period, 4 patients developed SSC due to other causes. Mean values of gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) were higher in the COVID-19 group than in the non-COVID-19 group (GGT: 2,689 U/L vs. 1,812 U/L and ALP: 1,445 U/L vs. 1,027 U/L), whereas intensive care treatment factors were comparable in both groups. Only the mean duration of mechanical ventilation was shorter in the COVID-19 group than in the non-COVID-19 group (22.1 days vs. 36.7 days). Liver elastography indicated a fast progression to liver cirrhosis with a mean liver stiffness of 17.3 kilopascals (kPa) in less than 12 weeks in the COVID-19 group. CONCLUSIONS Our data suggest a more severe course of SSC when caused by SARS-CoV-2. Reasons for this are probably multifactorial, including a direct cytopathogenic effect of the virus.
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24
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Gastrointestinal and Hepatobiliary Symptoms and Disorders with Long (Chronic) COVID Infection. Gastroenterol Clin North Am 2023; 52:139-156. [PMID: 36813422 PMCID: PMC9940919 DOI: 10.1016/j.gtc.2022.09.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2023]
Abstract
Long COVID is a novel syndrome characterizing new or persistent symptoms weeks after COVID-19 infection and involving multiple organ systems. This review summarizes the gastrointestinal and hepatobiliary sequelae of long COVID syndrome. It describes potential biomolecular mechanisms, prevalence, preventative measures, potential therapies, and health care and economic impact of long COVID syndrome, particularly of its gastrointestinal (GI) and hepatobiliary manifestations.
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25
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Abstract
PURPOSE OF REVIEW This review focuses on recent developments of histopathology in the most common biliary disorders affecting adults. The reader is referred to other sources for the specialized topics on paediatric populations and post liver transplantation. RECENT FINDINGS Fibrosis stage at diagnosis is an independent predictor of liver transplant-free survival in patients with primary biliary cholangitis. Immunohistochemistry might have an important role in predicting response to treatment. New histological scoring systems with excellent correlation with long-term clinical outcomes are being developed in primary sclerosing cholangitis (PSC). Quantification of fibrosis with collagen proportionate area can improve risk stratification and could be particularly useful to assess treatment response in PSC.Gene sequencing on cytology and intrabiliary biopsy may improve risk stratification for cholangiocarcinoma. Genetic variants of ATP8B1, ABCB11 and ABCB4 are relatively common in adults with cholestatic liver disease. New causes of cholestatic liver injury have recently been described. SUMMARY Histology is often not necessary for the diagnosis of biliary disease, but can provide important information that may assist the clinician in patients' management. Histopathology remains crucial to confirm a diagnosis of cholangiocarcinoma, and to identify the pattern of biliary injury in immune-mediated cholangiopathies and rarer pathological entities.
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Affiliation(s)
- Francesca Saffioti
- Oxford University Hospitals NHS Foundation Trust, Oxford.,UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London
| | - Rodrigo Vieira Motta
- Nuffield Department of Medicine, Investigative Medicine, University of Oxford, Oxford
| | - Alberto Quaglia
- Royal Free London NHS Foundation Trust and UCL Cancer Institute, London, UK
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26
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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
Abstract
BACKGROUND To investigate the possible influence of prolonged ketamine (K) or esketamine (ESK) infusion on the profile of liver cholestatic biomarkers in patients with COVID-19 infection. METHODS A retrospective analysis was performed on 135 patients with COVID-19 related ARDS who received prolonged K or ESK infusion. They were compared to 15 COVID-19 ICU patients who did not receive K/ESK while being mechanically ventilated and 108 COVID-19 patients who did not receive mechanical ventilation nor K/ESK. The profile of the liver function tests was analysed in the groups. RESULTS Peak values of ALP, GGT and bilirubin were higher in the K/ESK group, but not for AST and ALT. Peak values of ALP were significantly higher among patients who underwent mechanical ventilation and who received K/ESK, compared with mechanically ventilated patients who did not receive K/ESK. There was a correlation between these peak values and the cumulative dose and duration of K/ESK therapy. CONCLUSIONS Based on the observations of biliary anomalies in chronic ketamine abusers, prolonged exposure to ketamine sedation during mechanical ventilation may also be involved, in addition to viral infection causing secondary sclerosing cholangitis. The safety of prolonged ketamine sedation on the biliary tract requires further investigations.
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Affiliation(s)
- Julie Henrie
- grid.7942.80000 0001 2294 713XDepartment of Intensive Care, Cliniques St-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200 Brussels, Belgium
| | - Ludovic Gerard
- grid.7942.80000 0001 2294 713XDepartment of Intensive Care, Cliniques St-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200 Brussels, Belgium
| | - Caroline Declerfayt
- grid.7942.80000 0001 2294 713XDepartment of Intensive Care, Cliniques St-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200 Brussels, Belgium
| | - Adrienne Lejeune
- grid.7942.80000 0001 2294 713XDepartment of Intensive Care, Cliniques St-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200 Brussels, Belgium
| | - Pamela Baldin
- grid.7942.80000 0001 2294 713XDepartment of Pathology, Cliniques St-Luc, Université Catholique de Louvain, 1200 Brussels, Belgium
| | - Arnaud Robert
- grid.7942.80000 0001 2294 713XDepartment of Intensive Care, Cliniques St-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200 Brussels, Belgium
| | - Pierre-François Laterre
- grid.7942.80000 0001 2294 713XDepartment of Intensive Care, Cliniques St-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200 Brussels, Belgium
| | - Philippe Hantson
- Department of Intensive Care, Cliniques St-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200, Brussels, Belgium. .,Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Université Catholique de Louvain, 1200, Brussels, Belgium.
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27
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Anguiano-Albarran R, Cain D, Ashfaq M, Modi A, Gautam S. Multiorgan Failure and Omicron: A Suspected Case of Post-COVID-19 Cholangiopathy. Cureus 2023; 15:e35010. [PMID: 36938182 PMCID: PMC10021348 DOI: 10.7759/cureus.35010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/15/2023] [Indexed: 02/17/2023] Open
Abstract
Since the declaration of a global pandemic by the World Health Organization on March 11, 2020, coronavirus disease 2019 (COVID-19) has impacted millions worldwide. This complex disease process has been primarily associated with respiratory illness. As we continue to learn about COVID-19, there appears to be a growing spectrum of non-pulmonary manifestations. A major topic of interest is hepatic dysfunction related to COVID-19, specifically the growing number of cases involving acute liver failure in the setting of COVID-19. Here, we present a rare case of a patient with COVID-19 antibodies, negative inpatient COVID-19 testing, jaundice, and elusive multiorgan dysfunction.
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Affiliation(s)
- Ricardo Anguiano-Albarran
- Internal Medicine, Texas Christian University School of Medicine - Internal Medicine Residency Program, Fort Worth, USA
| | - Daniel Cain
- Internal Medicine, Texas Christian University School of Medicine - Internal Medicine Residency Program, Fort Worth, USA
| | - Mohammad Ashfaq
- Transplant Hepatology, Baylor Simmons Transplant Institute, Baylor Scott & White All Saints Medical Center, Fort Worth, USA
- Graduate Medical Education, Texas Christian University School of Medicine - Internal Medicine Residency Program, Fort Worth, USA
| | - Apurva Modi
- Transplant Hepatology, Baylor Simmons Transplant Institute, Baylor Scott & White All Saints Medical Center, Fort Worth, USA
- Graduate Medical Education, Texas Christian University School of Medicine - Internal Medicine Residency Program, Fort Worth, USA
| | - Shovendra Gautam
- Graduate Medical Education, Texas Christian University School of Medicine - Internal Medicine Residency Program, Fort Worth, USA
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28
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Abstract
SARS-CoV-2 is the viral agent of COVID-19, a pandemic that surfaced in 2019. Although predominantly a respiratory ailment, patients with COVID-19 can have gastrointestinal (GI) and hepatobiliary manifestations. These manifestations are often mild and transient, but they can be severe and consequential. In the GI tract, ischemic enterocolitis is the most common and significant consequence of COVID-19. In the liver, the reported pathologic findings may often be related to consequences of severe systemic viral infection, but reports of hepatitis presumed to be due to SARS-CoV-2 suggest that direct viral infection of the liver may be a rare complication of COVID-19. In both the GI tract and liver, lingering symptoms of GI or hepatic injury after resolution of pulmonary infection may be part of the evolving spectrum of long COVID.
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Affiliation(s)
- Angela R Shih
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
| | - Joseph Misdraji
- Department of Pathology, Yale New Haven Hospital, Yale University, New Haven, CT, 06510, USA.
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29
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Abstract
The coronavirus disease-2019 (COVID-19) pandemic has had a large impact on patients with chronic liver disease (CLD) and liver transplantation (LT) recipients. Patients with advanced CLD are at a significantly increased risk of poor outcomes in the setting of severe acute respiratory syndrome coronavirus 2 infection. The pandemic has also considerably altered the management and care that is provided to patients with CLD, pre-LT patients, and LT recipients. Vaccination against COVID-19 protects patients with CLD and LT recipients from adverse outcomes and is safe in these patients; however, vaccine efficacy may be reduced in LT recipients and other immunosuppressed patients.
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30
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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; 11:29-37. [DOI: 10.13105/wjma.v11.i1.29] [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: 08/25/2022] [Revised: 10/13/2022] [Accepted: 11/23/2022] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND The recent and still ongoing pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entailed various long-term complications, including post-infectious cholangiopathy.
AIM To identify the available studies concerning post-coronavirus disease 2019 (COVID-19) cholangiopathy.
METHODS An extensive bibliographical search was carried out in PubMed and in Cochrane Library to identify the articles (retrospective and prospective studies, cohort studies, case series and case reports) published between January 1, 2020 and August 22, 2022, using both MeSH terms and free-language keywords: cholangiopathy; COVID-19; post-COVID-19 cholangiopathy; SARS-CoV-2.
RESULTS Thirteen studies fulfilled the inclusion criteria, which included 64 patients suffering from this condition. The patients were male in 82.8% of cases. Liver transplant was executed in 6 patients and scheduled in 7 patients, while 2 patients refused the surgical approach. Therefore in 23.4% of the cases, performing this procedure appeared to be necessary.
CONCLUSION This review has revealed that generally the involvement of the liver in the course of SARS-CoV-2 infection is mild and transient, inducing cholestasis of cholangiocytes but can also be severe enough to cause organ failure in some cases.
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Affiliation(s)
- Maddalena Zippi
- Unit of Gastroenterology and Digestive Endoscopy, Sandro Pertini Hospital, Rome 00157, Italy
| | - Sirio Fiorino
- Unit of Internal Medicine, Maggiore Hospital, Local Health Unit of Bologna, Bologna 40133, Italy
| | - Wandong Hong
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Dario de Biase
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | | | - Alfonso Grottesi
- Unit of General Surgery, Sandro Pertini Hospital, Rome 00157, Italy
| | | | - Pietro Crispino
- Unit of Emergency Medicine, Santa Maria Goretti Hospital, Latina 04100, Italy
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Sarkis Y, Saleem N, Vuppalanchi R, Gromski M. COVID-Associated Cast-Forming Cholangiopathy: A Commentary on Disease Mechanism, Treatment, and Prognosis. Hepat Med 2023; 15:27-32. [PMID: 37013139 PMCID: PMC10066716 DOI: 10.2147/hmer.s384176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Accepted: 03/23/2023] [Indexed: 04/05/2023] Open
Abstract
The complete impact of COVID-19 infection continues to develop since the onset of the COVID-19 pandemic. COVID-19 cholangiopathy has been recently described in a subset of patients who recovered from severe COVID-19 infection. The most common phenotype of patients suffering from COVID-19 cholangiopathy had severe infection requiring a stay in the intensive care unit, mechanical ventilation and vasopressor medications. Patients with COVID-cholangiopathy present with severe and prolonged cholestatic liver injury. In cases where biliary cast formation is identified, we defined the entity as "COVID-19 cast-forming cholangiopathy". This subset of COVID-19 cholangiopathy is not well understood and there are no standardized diagnosis or management to this date. The reported clinical outcomes are variable, from resolution of symptoms and liver test abnormalities to liver transplant and death. In this commentary, we discuss the proposed pathophysiology, diagnosis, management, and prognosis of this disease.
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Affiliation(s)
- Yara Sarkis
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Nasir Saleem
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Raj Vuppalanchi
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Mark Gromski
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
- Correspondence: Mark Gromski, Gastroenterology and Hepatology Department, Indiana University Hospital, 550 N. University Blvd, Suite 1634, Indianapolis, IN, 46202, USA, Tel +317-944-0925, Fax +317-968-1265, Email
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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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Affiliation(s)
- Stephan Schmid
- Klinik und Poliklinik für Innere Medizin 1, Gastroenterologie, Endokrinologie, Infektiologie und Rheumatologie, Universitätsklinikum Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Deutschland
| | - Arne Kandulski
- Klinik und Poliklinik für Innere Medizin 1, Gastroenterologie, Endokrinologie, Infektiologie und Rheumatologie, Universitätsklinikum Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Deutschland
| | - Martina Müller-Schilling
- Klinik und Poliklinik für Innere Medizin 1, Gastroenterologie, Endokrinologie, Infektiologie und Rheumatologie, Universitätsklinikum Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Deutschland
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Fatima I, Duong N. The impact of COVID-19 on liver transplantation: challenges and perspectives. Therap Adv Gastroenterol 2023; 16:17562848231171452. [PMID: 37180361 PMCID: PMC10172841 DOI: 10.1177/17562848231171452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Accepted: 04/06/2023] [Indexed: 05/16/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic presented unique challenges to patients with decompensated cirrhosis awaiting transplant, with respect to accessing medical facilities for routine clinic visits, imaging, laboratory workup, or endoscopies. There was a delay in organ procurement that led to a decrease in the number of liver transplants (LTs) and an increase in the morality of waitlisted patients at the beginning of the pandemic. LT numbers later equalized to pre-pandemic numbers due to combined efforts and adaptability of transplant centers as well as dynamic guidelines. Due to being immunosuppressed, the demographics of LT patients were at an increased risk of infection. Although there is a higher rate of mortality and morbidity in patients with chronic liver disease, LT itself is not a risk factor for mortality in COVID-19. There was no difference in overall mortality in LT patients compared to non-LT patients, and mortality risk factors were the same: age, hypertension, diabetes, obesity, and chronic kidney disease. The most common causes of death were respiratory complications. Liver-related deaths were reported in 1.6% of patients. The optimal timing of liver transplantation post-infection depends on various factors, such as the severity of liver injury, the presence of comorbidities, and the progression of the underlying liver disease. There is not enough data available on COVID-19 cholangiopathy and the number of cases that will be seen in the future that will require LT. There are some concerns of lower immunogenicity of COVID-19 vaccines in LT patients but available evidence suggests that the vaccines are safe and well-tolerated.
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Affiliation(s)
| | - Nikki Duong
- Department of Gastroenterology, Hepatology and
Nutrition, Virginia Commonwealth University Medical Center, Richmond, VA,
USA
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Ludwig DR, Anderson MA, Itani M, Sharbidre KG, Lalwani N, Paspulati RM. Secondary sclerosing cholangitis: mimics of primary sclerosing cholangitis. Abdom Radiol (NY) 2023; 48:151-165. [PMID: 35585354 PMCID: PMC9116710 DOI: 10.1007/s00261-022-03551-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 05/01/2022] [Accepted: 05/02/2022] [Indexed: 01/21/2023]
Abstract
Sclerosing cholangitis is a chronic cholestatic disease characterized by stricturing, beading, and obliterative fibrosis of the bile ducts. Sclerosing cholangitis is considered primary (PSC) if no underlying etiology is identified or secondary (SSC) if related to another identifiable cause. In this article, we will review the clinical features, pathogenesis, diagnosis, and imaging findings of PSC and SSC, with an emphasis on features that may aid in the distinction of these entities. We will also discuss various etiologies of SSC including recurrent pyogenic cholangitis, other infectious etiologies, ischemic damage, toxic insults, and immunologic, congenital, and miscellaneous causes, highlighting the unique imaging findings and clinical context of each diagnosis.
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Affiliation(s)
- Daniel R. Ludwig
- grid.4367.60000 0001 2355 7002Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, Campus Box 8131, Saint Louis, MO 63110 USA
| | - Mark A. Anderson
- grid.38142.3c000000041936754XDepartment of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA USA
| | - Malak Itani
- grid.4367.60000 0001 2355 7002Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, Campus Box 8131, Saint Louis, MO 63110 USA
| | - Kedar G. Sharbidre
- grid.265892.20000000106344187Department of Radiology, The University of Alabama at Birmingham, Birmingham, AL USA
| | - Neeraj Lalwani
- grid.224260.00000 0004 0458 8737Department of Radiology, Virginia Commonwealth University, Richmond, VA USA
| | - Raj M. Paspulati
- grid.67105.350000 0001 2164 3847Department of Radiology, Case Western Reserve University, Cleveland, OH USA
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Steiner J, Kaufmann-Bühler AK, Fuchsjäger M, Schemmer P, Talakić E. Secondary sclerosing cholangitis in a young COVID-19 patient resulting in death: A case report. World J Gastrointest Surg 2022; 14:1411-1417. [PMID: 36632122 PMCID: PMC9827572 DOI: 10.4240/wjgs.v14.i12.1411] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/28/2022] [Accepted: 10/05/2022] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND With the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019 in Wuhan, China, liver injury in patients with coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection has been regularly reported in the literature. There are a growing number of publications describing the occurrence of secondary sclerosing cholangitis (SSC) after SARS-CoV-2 infection in various cases. We present a case of sudden onset SSC in a critically ill patient (SSC-CIP) following COVID-19 infection who was previously healthy.
CASE SUMMARY A 33-year old female patient was admitted to our University Hospital due to increasing shortness of breath. A prior rapid antigen test showed a positive result for SARS-CoV-2. The patient had no known preexisting conditions. With rapidly increasing severe hypoxemia she required endotracheal intubation and developed the need for veno-venous extracorporeal membrane oxygenation in a setting of acute respiratory distress syndrome. During the patient´s 154-d stay in the intensive care unit and other hospital wards she underwent hemodialysis and extended polypharmaceutical treatment. With increasing liver enzymes and the development of signs of cholangiopathy on magnetic resonance cholangiopancreatography (MRCP) as well as endoscopic retrograde cholangiopancreatography (ERCP), the clinical setting was suggestive of SSC. At an interdisciplinary meeting, the possibility of orthotopic liver transplantation and additional kidney transplantation was discussed due to the constant need for hemodialysis. Following a deterioration in her general health and impaired respiratory function with a reduced chance of successful surgery and rehabilitation, the plan for transplantation was discarded. The patient passed away due to multiorgan failure.
CONCLUSION SSC-CIP seems to be a rare but serious complication in patients with SARS-CoV-2 infection, of which treating physicians should be aware. Imaging with MRCP and/or ERCP seems to be indicated and a valid method for early diagnosis. Further studies on the effects of early and late SSC in (post-) COVID-19 patients needs to be performed.
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Affiliation(s)
- Jakob Steiner
- Department of General Radiology, Medical University of Graz, Graz 8036, Austria
| | | | - Michael Fuchsjäger
- Department of General Radiology, Medical University of Graz, Graz 8036, Austria
| | - Peter Schemmer
- Department of General Visceral and Transplant Surgery, Medical University of Graz, Graz 8036, Austria
| | - Emina Talakić
- Department of General Radiology, Medical University of Graz, Graz 8036, Austria
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Hartl L, Haslinger K, Angerer M, Semmler G, Schneeweiss-Gleixner M, Jachs M, Simbrunner B, Bauer DJM, Eigenbauer E, Strassl R, Breuer M, Kimberger O, Laxar D, Lampichler K, Halilbasic E, Stättermayer AF, Ba-Ssalamah A, Mandorfer M, Scheiner B, Reiberger T, Trauner M. Progressive cholestasis and associated sclerosing cholangitis are frequent complications of COVID-19 in patients with chronic liver disease. Hepatology 2022; 76:1563-1575. [PMID: 35596929 PMCID: PMC9347407 DOI: 10.1002/hep.32582] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 04/22/2022] [Accepted: 05/16/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS Cholestasis is associated with disease severity and worse outcome in COVID-19. Cases of secondary sclerosing cholangitis (SSC) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been described. APPROACH AND RESULTS Hospitalized patients with COVID-19 between 03/2020 and 07/2021 were included. Patients were stratified as having (i) no chronic liver disease (CLD), (ii) non-advanced CLD (non-ACLD), or (iii) advanced CLD (ACLD). Patients with CLD and non-COVID-19 pneumonia were matched to patients with CLD and COVID-19 as a control cohort. Liver chemistries before (Pre) and at first, second, and third blood withdrawal after SARS-CoV-2 infection (T1-T3) and at last available time point (last) were recorded. A total of 496 patients were included. In total, 13.1% (n = 65) had CLD (non-ACLD: 70.8%; ACLD: 29.2%); the predominant etiology was NAFLD/NASH (60.0%). COVID-19-related liver injury was more common among patients with CLD (24.6% vs. 10.6%; p = 0.001). After SARS-CoV-2 infection, patients with CLD exhibited progressive cholestasis with persistently increasing levels of alkaline phosphatase (Pre: 91.0 vs. T1: 121.0 vs. last: 175.0 U/L; p < 0.001) and gamma-glutamyl transferase (Pre: 95.0 vs. T1: 135.0 vs. last: 202.0 U/L; p = 0.001). A total of 23.1% of patients with CLD (n = 15/65) developed cholestatic liver failure (cholestasis plus bilirubin ≥6 mg/dl) during COVID-19, and 15.4% of patients (n = 10/65) developed SSC. SSC was significantly more frequent among patients with CLD and COVID-19 than in patients with CLD and non-COVID-19 pneumonia (p = 0.040). COVID-19-associated SSC occurred predominantly in patients with NAFLD/NASH and metabolic risk factors. A total of 26.3% (n = 5/19) of patients with ACLD experienced hepatic decompensation after SARS-CoV-2 infection. CONCLUSIONS About 20% of patients with CLD develop progressive cholestasis after SARS-CoV-2 infection. Patients with NAFLD/NASH and metabolic risk factors are at particular risk for developing cholestatic liver failure and/or SSC after COVID-19.
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Affiliation(s)
- Lukas Hartl
- Division of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria.,Vienna Hepatic Hemodynamic LabDivision of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
| | - Katharina Haslinger
- Division of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria.,Vienna Hepatic Hemodynamic LabDivision of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
| | - Martin Angerer
- Division of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria.,Vienna Hepatic Hemodynamic LabDivision of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
| | - Georg Semmler
- Division of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria.,Vienna Hepatic Hemodynamic LabDivision of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
| | | | - Mathias Jachs
- Division of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria.,Vienna Hepatic Hemodynamic LabDivision of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
| | - Benedikt Simbrunner
- Division of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria.,Vienna Hepatic Hemodynamic LabDivision of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria.,Christian Doppler Lab for Portal Hypertension and Liver FibrosisMedical University of ViennaViennaAustria
| | - David Josef Maria Bauer
- Division of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria.,Vienna Hepatic Hemodynamic LabDivision of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
| | - Ernst Eigenbauer
- IT-Systems and CommunicationsMedical University of ViennaViennaAustria
| | - Robert Strassl
- Division of Clinical VirologyDepartment of Laboratory MedicineMedical University of ViennaViennaAustria
| | - Monika Breuer
- Division of Clinical VirologyDepartment of Laboratory MedicineMedical University of ViennaViennaAustria
| | - Oliver Kimberger
- Department of AnaesthesiaIntensive Care Medicine and Pain MedicineMedical University of ViennaViennaAustria
| | - Daniel Laxar
- Department of AnaesthesiaIntensive Care Medicine and Pain MedicineMedical University of ViennaViennaAustria
| | - Katharina Lampichler
- Department of Biomedical Imaging and Image-Guided TherapyMedical University of ViennaViennaAustria
| | - Emina Halilbasic
- Division of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
| | - Albert Friedrich Stättermayer
- Division of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria.,Vienna Hepatic Hemodynamic LabDivision of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
| | - Ahmed Ba-Ssalamah
- Department of Biomedical Imaging and Image-Guided TherapyMedical University of ViennaViennaAustria
| | - Mattias Mandorfer
- Division of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria.,Vienna Hepatic Hemodynamic LabDivision of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
| | - Bernhard Scheiner
- Division of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria.,Vienna Hepatic Hemodynamic LabDivision of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
| | - Thomas Reiberger
- Division of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria.,Vienna Hepatic Hemodynamic LabDivision of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria.,Christian Doppler Lab for Portal Hypertension and Liver FibrosisMedical University of ViennaViennaAustria
| | - Michael Trauner
- Division of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
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Rela M, Rajakannu M, Veerankutty FH, Vij M, Rammohan A. First report of auxiliary liver transplantation for severe cholangiopathy after SARS-CoV-2 respiratory infection. Am J Transplant 2022; 22:3143-3145. [PMID: 35929565 PMCID: PMC9538267 DOI: 10.1111/ajt.17165] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/20/2022] [Accepted: 08/02/2022] [Indexed: 01/25/2023]
Abstract
Post-coronavirus disease 2019 (COVID-19) cholangiopathy (PCC) is a new entity observed in patients recovering from severe COVID-19 pneumonia. Most patients recover with cholestasis improving over a period of time. In some patients, cholestasis is severe and persists or progresses to liver failure necessitating liver transplant. We present a previously healthy 50-year-old man who developed PCC with peak total bilirubin of 42.4 mg/dl and did not improve with medical management. He underwent living donor auxiliary right lobe liver transplantation. He recovered well after transplant and remains asymptomatic at 6 months follow-up with good graft function and recovering function in native liver remnant.
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Affiliation(s)
- Mohamed Rela
- The Institute of Liver Disease & Transplantation, Dr Rela Institute & Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India,Correspondence Mohamed Rela, Dr. Rela Institute and Medical Centre, No.7, CLC Works Road, Chromepet, Chennai 600044, India.
| | - Muthukumarassamy Rajakannu
- The Institute of Liver Disease & Transplantation, Dr Rela Institute & Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Fadl H. Veerankutty
- The Institute of Liver Disease & Transplantation, Dr Rela Institute & Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Mukul Vij
- The Institute of Liver Disease & Transplantation, Dr Rela Institute & Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Ashwin Rammohan
- The Institute of Liver Disease & Transplantation, Dr Rela Institute & Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
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Ferreira FB, Mourato M, Bragança S, Paulo JB, Sismeiro R, Pereira A, Mónica AN, Lourenço LC, Cardoso M. COVID-19-associated secondary sclerosing cholangitis - A case series of 4 patients. Clin Res Hepatol Gastroenterol 2022; 46:102048. [PMID: 36347499 PMCID: PMC9636600 DOI: 10.1016/j.clinre.2022.102048] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 10/24/2022] [Accepted: 11/03/2022] [Indexed: 11/08/2022]
Abstract
We report a case series of four patients diagnosed with COVID-19-associated secondary sclerosing cholangitis (SSC), a recently described rare late complication of severe COVID-19. Following prolonged stays in the intensive care unit, these patients developed marked sustained cholestasis and jaundice despite clinical improvement. Cholangiography showed beaded appearance of intra-hepatic bile ducts and bile casts were removed in one patient. None of the patients reached normalization of liver enzymes and at least one progressed to liver cirrhosis (follow-up time of 11 to 16 months). COVID-19-associated SSC has a dismal prognosis with rapid progression to advanced chronic liver disease.
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Affiliation(s)
- Filipa Bordalo Ferreira
- Gastroenterology department, Hospital Professor Doutor Fernando Fonseca, IC 19, 2720-276 Amadora, Portugal.
| | - Margarida Mourato
- Internal Medicine department, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal, IC 19, 2720-276 Amadora, Portugal
| | - Sofia Bragança
- Gastroenterology department, Hospital Professor Doutor Fernando Fonseca, IC 19, 2720-276 Amadora, Portugal
| | - Joana Batista Paulo
- Internal Medicine department, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal, IC 19, 2720-276 Amadora, Portugal
| | - Rita Sismeiro
- Internal Medicine department, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal, IC 19, 2720-276 Amadora, Portugal
| | - André Pereira
- Pathology department, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal, IC 19, 2720-276 Amadora, Portugal
| | - Ana Nassauer Mónica
- Radiology department, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal. IC 19, 2720-276 Amadora, Portugal
| | - Luís Carvalho Lourenço
- Gastroenterology department, Hospital Professor Doutor Fernando Fonseca, IC 19, 2720-276 Amadora, Portugal
| | - Mariana Cardoso
- Gastroenterology department, Hospital Professor Doutor Fernando Fonseca, IC 19, 2720-276 Amadora, Portugal
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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
Abstract
OBJECTIVES Post COVID-19 cholangiopathy is a rare but poorly understood and serious complication of COVID-19 infection. We sought to better understand the epidemiology, mechanism of action, histology, imaging findings and outcomes of post-COVID-19 cholangiopathy. METHODS We searched PubMed, Cochrane Library, Embase, and Web of Science from December 2019 to December 2021. Mesh words used "post-Covid-19 cholangiopathy", "COVID-19 liver injury"," Covid-19 and cholangiopathy", and COVID-19 liver disease". The data on epidemiology, mechanism of action, histology, imaging findings and outcomes were collected. RESULTS Post COVID-19 cholangiopathy was reported in 30 cases during the study period. The mean (standard deviation [SD]) age was 53.7 (5). Men accounted for cases (83.3%). All patients had required intensive level of care and mechanical ventilation. Mean (SD) number of days from COVID infection to severe disease or liver disease was 63.5(38). Peak mean (SD) alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, total bilirubin were 2014 (831.8) U/L, 1555 (2432.8) U/L, 899.72 (1238.6) U/L, and 10.32 (9.32) mg/dl, respectively. Four patients successfully underwent liver transplantation. CONCLUSION Post COVID-19 cholangiopathy is a severe and progressive complication of COVID-19 infection. More research is needed to better understand the pathophysiology and best treatment approach. Clinicians should suspect post COVID-19 cholangiopathy in patients with cholestatic liver injury following COVID-19 infection.
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40
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Cho JY, Lee YS, Kim SS, Song DS, Lee JH, Kim JH. Forms of cholangitis to be considered after SARS-CoV-2 infection. Clin Mol Hepatol 2022; 28:929-930. [PMID: 36096495 PMCID: PMC9597223 DOI: 10.3350/cmh.2022.0260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 08/31/2022] [Indexed: 01/05/2023] Open
Affiliation(s)
- Ju-Yeon Cho
- Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, Korea
| | - Young-Sun Lee
- Department of Internal Medicine, Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Soon Sun Kim
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Do Seon Song
- Department of Gastroenterology, St. Vincent’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Guro Hospital, Korea University College of Medicine, Seoul, Korea,Corresponding author : Ji Hoon Kim Department of Internal Medicine, Korea University Medical Center, 148 Gurodong-ro, Guro-gu, Seoul 08308, Korea Tel: +82-2-2626-3011, Fax: +82-2-2626-1038, E-mail:
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41
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Abstract
OBJECTIVES Severe acute respiratory syndrome coronavirus 2, the novel coronavirus responsible for coronavirus disease (COVID-19), has been a major cause of morbidity and mortality worldwide. Gastrointestinal and hepatic manifestations during acute disease have been reported extensively in the literature. Post-COVID-19 cholangiopathy has been increasingly reported in adults. In children, data are sparse. Our aim was to describe pediatric patients who recovered from COVID-19 and later presented with liver injury. METHODS This is a retrospective case series study of pediatric patients with post-COVID-19 liver manifestations. We collected data on demographics, medical history, clinical presentation, laboratory results, imaging, histology, treatment, and outcome. RESULTS We report 5 pediatric patients who recovered from COVID-19 and later presented with liver injury. Two types of clinical presentation were distinguishable. Two infants aged 3 and 5 months, previously healthy, presented with acute liver failure that rapidly progressed to liver transplantation. Their liver explant showed massive necrosis with cholangiolar proliferation and lymphocytic infiltrate. Three children, 2 aged 8 years and 1 aged 13 years, presented with hepatitis with cholestasis. Two children had a liver biopsy significant for lymphocytic portal and parenchyma inflammation, along with bile duct proliferations. All 3 were started on steroid treatment; liver enzymes improved, and they were weaned successfully from treatment. For all 5 patients, extensive etiology workup for infectious and metabolic etiologies was negative. CONCLUSIONS We report 2 distinct patterns of potentially long COVID-19 liver manifestations in children with common clinical, radiological, and histopathological characteristics after a thorough workup excluded other known etiologies.
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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: 6] [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: 01/28/2022] [Revised: 04/04/2022] [Accepted: 08/16/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The global coronavirus disease 2019 (COVID-19) pandemic has caused more than 5 million deaths. Multiorganic involvement is well described, including liver disease. In patients with critical COVID-19, a new entity called "post-COVID-19 cholangiopathy" has been described.
CASE SUMMARY Here, we present three patients with severe COVID-19 that subsequently developed persistent cholestasis and chronic liver disease. All three patients required intensive care unit admission, mechanical ventilation, vasopressor support, and broad spectrum antibiotics due to secondary infections. Liver transplant protocol was started for two of the three patients.
CONCLUSION Severe COVID-19 infection should be considered a potential risk factor for chronic liver disease and liver transplantation.
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Affiliation(s)
- Juan M Mayorquín-Aguilar
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
| | - Aldo Lara-Reyes
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
| | - Luis Alberto Revuelta-Rodríguez
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
| | - Nayelli C Flores-García
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
| | - Astrid Ruiz-Margáin
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
| | | | - Ricardo Ulises Macías-Rodríguez
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
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43
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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]
Abstract
AbstractSecondary sclerosing cholangitis in critically ill patients (SC-CIP) is a rare disease characterized by chronic cholestasis. The underlying pathophysiology of SC-CIP is not fully understood, and prognosis in severe cases remains poor with liver transplantation remaining the only curative treatment option. There is a growing amount of literature describing patients with chronic cholangiopathy after COVID-19 infection. The vast majority of the patients described in these reports were male and had a poor outcome. While the exact percentage of patients with COVID-19-related SC-CIP cannot be estimated accurately due to a lack of larger studies, an increase in patients with long-term complications of chronic cholestatic liver disease after severe COVID19-pneumonia can be expected in the upcoming years. Treatment options remain limited and further research is needed to improve the dismal prognosis of SC-CIP. Here, we present the cases of two patients who developed SC-CIP after prolonged intensive care unit stay due to severe COVID-19 pneumonia. Both patients required invasive ventilation for 31 and 141 days, respectively, as well as extra-corporal membrane oxygenation for 23 and 87 days. The patients suffered from jaundice and severe pruritus, and typical features of SC-CIP were present by MRCP and ERC. Repeated removal of biliary casts resulted in some alleviation of their clinical symptoms, but cholestasis parameters remain elevated. Furthermore, an increased liver stiffness was indicative of advanced fibrosis in both patients. In addition to these two case reports, we provide a concise review of the literature of SC-CIP after COVID-19 infection and discuss risk factors, treatment options and prognosis.
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44
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Hoffmann C, Gerber PA, Cavelti-Weder C, Licht L, Kotb R, Al Dweik R, Cherfane M, Bornstein SR, Perakakis N. Liver, NAFLD and COVID-19. Horm Metab Res 2022; 54:522-531. [PMID: 35468630 DOI: 10.1055/a-1834-9008] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Coronavirus disease 2019 (COVID-19) is characterized by a wide clinical spectrum that includes abnormalities in liver function indicative of liver damage. Conversely, people with liver diseases are at higher risk of severe COVID-19. In the current review, we summarize first the epidemiologic evidence describing the bidirectional relationship between COVID-19 and liver function/liver diseases. Additionally, we present the most frequent histologic findings as well as the most important direct and indirect mechanisms supporting a COVID-19 mediated liver injury. Furthermore, we focus on the most frequent liver disease in the general population, non-alcoholic or metabolic-associated fatty liver disease (NAFLD/MAFLD), and describe how COVID-19 may affect NAFLD/MAFLD development and progression and conversely how NAFLD/MAFLD may further aggravate a COVID-19 infection. Finally, we present the long-term consequences of the pandemic on the development and management of NAFLD.
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Affiliation(s)
- Carlotta Hoffmann
- University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany, Department of Internal Medicine III, Dresden, Germany
| | - Philipp A Gerber
- University Hospital Zurich (USZ) and University of Zurich (UZH), Switzerland, Department of Endocrinology, Diabetology and Clinical Nutrition, Zurich, Switzerland
| | - Claudia Cavelti-Weder
- University Hospital Zurich (USZ) and University of Zurich (UZH), Switzerland, Department of Endocrinology, Diabetology and Clinical Nutrition, Zurich, Switzerland
| | - Louisa Licht
- University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany, Department of Internal Medicine III, Dresden, Germany
| | - Reham Kotb
- Abu Dhabi University, Abu Dhabi, United Arab Emirates, College of Health Sciences, Abu Dhabi, United Arab Emirates
| | - Rania Al Dweik
- Abu Dhabi University, Abu Dhabi, United Arab Emirates, Department of Public Health, Abu Dhabi, United Arab Emirates
| | - Michele Cherfane
- Abu Dhabi University, Abu Dhabi, United Arab Emirates, College of Health Sciences, Abu Dhabi, United Arab Emirates
| | - Stefan R Bornstein
- University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany, Department of Internal Medicine III, Dresden, Germany
| | - Nikolaos Perakakis
- University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany, Department of Internal Medicine III, Dresden, Germany
- University Hospital and Faculty of Medicine, TU Dresden, Dresden, Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, Dresden, Germany
- Neuherberg, German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
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45
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Sonkar C, Hase V, Banerjee D, Kumar A, Kumar R, Jha HC. Post COVID-19 complications, adjunct therapy explored, and steroidal after effects. CAN J CHEM 2022; 100:459-474. [DOI: 10.1139/cjc-2021-0247] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
For COVID-19 survivors, defeating the virus is just the beginning of a long road to recovery. The inducibility and catastrophic effects of the virus are distributed across multiple organs. The induction of cytokine storms in COVID-19 patients is due to the interaction of the SARS-CoV-2 virus and the host receptor, leading to various immunopathological consequences that may eventually lead to death. So far, COVID-19 has affected tons of people across the world, but there is still no effective treatment. Patients facing complications of COVID-19 after recovery have shown extensive clinical symptoms similar to that of patients recovering from previously circulating coronaviruses. Previous knowledge and literature have opened up ways to treat this disease and manage post-COVID-19 complications, which pose a severe challenge to the health system globally and may exacerbate the fragmentation of diseases. The use of steroids as a treatment has resulted in various health problems and side-effects in COVID-19 patients. This review discusses various post-COVID-19 complications observed and adjunctive therapies used along with common COVID-19 treatment and spotlights their side effects and consequences. This review provides the latest literature on COVID-19, which emphasizes the subsequent complications in various organs, side effects of drugs, and alternative regimens used to treat COVID-19.
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Affiliation(s)
- Charu Sonkar
- Department of Biosciences and Biomedical Engineering (BSBE), Indian Institute of Technology Indore, Khandwa Road, Simrol, Indore 453552, India
| | - Vaishnavi Hase
- School of Biotechnology and Bioinformatics, D.Y. Patil Deemed to be University, Navi Mumbai 400614, India
| | - Durba Banerjee
- School of Biotechnology (SOB), Gautam Buddha University (Delhi NCR), Yamuna Expressway, Gautam Buddha Nagar, Greater Noida, Uttar Pradesh 201312, India
| | - Awanish Kumar
- Department of Biotechnology, National Institute of Technology, Raipur 492010, India
| | - Rajesh Kumar
- Department of Physics, Indian Institute of Technology, Indore 453552, India
| | - Hem Chandra Jha
- Department of Biosciences and Biomedical Engineering (BSBE), Indian Institute of Technology Indore, Khandwa Road, Simrol, Indore 453552, India
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46
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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]
Abstract
Multiple studies and extensive clinical experience have shown that COVID-19 can impact the hepatobiliary system, with most reports describing primarily hepatocellular injury with elevations of aspartate aminotransferase and alanine aminotransferase. In addition to hepatocellular injury, recent literature has described a pattern of severe biliary tract injury resulting in patients with COVID-19. This novel syndrome, termed COVID-19 cholangiopathy, may have severe consequences for affected patients. This article will examine the literature describing this novel entity, its relationship to secondary sclerosing cholangitis, clinical outcomes, and proposed mechanisms underlying this form of biliary injury.
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Affiliation(s)
- Saamia Faruqui
- Department of Medicine, NYU Grossman School of Medicine, New York, New York
| | - Krishna Shanbhogue
- Department of Radiology, NYU Grossman School of Medicine, New York, New York
| | - Ira M. Jacobson
- Department of Medicine, NYU Grossman School of Medicine, New York, New York
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47
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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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Affiliation(s)
- Angela R Shih
- Department of Pathology and Laboratory Medicine (Shih, Deshpande, Misdraji), at the Massachusetts General Hospital, Boston, Massachusetts
| | - Dilara Hatipoglu
- The Department of Medicine (Hatipoglu, Wilechansky, Chung), at the Massachusetts General Hospital, Boston, Massachusetts
| | - Robert Wilechansky
- Liver Center and Gastrointestinal Division (Wilechansky, Chung) at the Massachusetts General Hospital, Boston, Massachusetts.,The Department of Medicine (Hatipoglu, Wilechansky, Chung), at the Massachusetts General Hospital, Boston, Massachusetts
| | - Reece Goiffon
- Department of Radiology (Goiffon), at the Massachusetts General Hospital, Boston, Massachusetts
| | - Vikram Deshpande
- Department of Pathology and Laboratory Medicine (Shih, Deshpande, Misdraji), at the Massachusetts General Hospital, Boston, Massachusetts
| | - Joseph Misdraji
- Department of Pathology and Laboratory Medicine (Shih, Deshpande, Misdraji), at the Massachusetts General Hospital, Boston, Massachusetts
| | - Raymond T Chung
- Liver Center and Gastrointestinal Division (Wilechansky, Chung) at the Massachusetts General Hospital, Boston, Massachusetts.,The Department of Medicine (Hatipoglu, Wilechansky, Chung), at the Massachusetts General Hospital, Boston, Massachusetts
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48
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Hartl L, Haslinger K, Angerer M, Jachs M, Simbrunner B, Bauer DJM, Semmler G, Scheiner B, Eigenbauer E, Strassl R, Breuer M, Kimberger O, Laxar D, Trauner M, Mandorfer M, Reiberger T. Age-adjusted mortality and predictive value of liver chemistries in a Viennese cohort of COVID-19 patients. Liver Int 2022; 42:1297-1307. [PMID: 35412018 PMCID: PMC9115240 DOI: 10.1111/liv.15274] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 04/01/2022] [Accepted: 04/10/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS The coronavirus disease of 2019 (COVID-19) causes considerable mortality worldwide. We aimed to investigate the frequency and predictive role of abnormal liver chemistries in different age groups. METHODS Patients with positive severe acute respiratory distress syndrome-coronavirus-2 (SARS-CoV-2) polymerase chain reaction (PCR) test between 03/2020-07/2021 at the Vienna General Hospital were included. Patients were stratified for age: 18-39 vs. 40-69 vs. ≥70 years (y). Aspartate aminotransferase (AST), alanine-aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and total bilirubin (BIL) were recorded. RESULTS 900 patients (18-39 years: 32.2%, 40-69 years: 39.7%, ≥70 years: 28.1%) were included. Number of comorbidities, median D-dimer and C-reactive protein increased with age. During COVID-19, AST/ALT and ALP/GGT levels significantly increased. Elevated hepatocellular transaminases (AST/ALT) and cholestasis parameters (ALP/GGT/BIL) were observed in 40.3% (n = 262/650) and 45.0% (n = 287/638) of patients respectively. Liver-related mortality was highest among patients with pre-existing decompensated liver disease (28.6%, p < .001). 1.7% of patients without pre-existing liver disease died of liver-related causes, that is consequences of hepatic dysfunction or acute liver failure. Importantly, COVID-19-associated liver injury (16.0%, p < .001), abnormal liver chemistries and liver-related mortality (6.5%, p < .001) were most frequent among 40-69 years old patients. Elevated AST and BIL after the first positive SARS-CoV-2 PCR independently predicted mortality in the overall cohort and in 40-69 years old patients. CONCLUSIONS Almost half of the COVID-19 patients exhibit abnormal hepatocellular and cholestasis-related liver chemistries with 40-69 years old patients being at particularly high risk for COVID-19-related liver injury and liver-related mortality. Elevated AST and BIL after SARS-CoV-2 infection are independent predictors of mortality, especially in patients aged 40-69 years.
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Affiliation(s)
- Lukas Hartl
- Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
| | - Katharina Haslinger
- Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
| | - Martin Angerer
- Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
| | - Mathias Jachs
- Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
| | - Benedikt Simbrunner
- Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria,Christian Doppler Lab for Portal Hypertension and Liver FibrosisMedical University of ViennaViennaAustria
| | - David J. M. Bauer
- Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
| | - Georg Semmler
- Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
| | - Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
| | - Ernst Eigenbauer
- IT‐Systems and CommunicationsMedical University of ViennaViennaAustria
| | - Robert Strassl
- Division of Clinical Virology, Department of Laboratory MedicineMedical University of ViennaViennaAustria
| | - Monika Breuer
- Division of Clinical Virology, Department of Laboratory MedicineMedical University of ViennaViennaAustria
| | - Oliver Kimberger
- Department of Anaesthesia, Intensive Care Medicine and Pain MedicineMedical University of ViennaViennaAustria
| | - Daniel Laxar
- Department of Anaesthesia, Intensive Care Medicine and Pain MedicineMedical University of ViennaViennaAustria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria,Christian Doppler Lab for Portal Hypertension and Liver FibrosisMedical University of ViennaViennaAustria
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49
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Abstract
PURPOSE OF REVIEW The objective of this review is to examine the epidemiology and pathogenesis of liver injury in coronavirus disease 2019 (COVID-19) and the impact of COVID-19 on patients with chronic liver disease (CLD) and liver transplant recipients. RECENT FINDINGS Abnormal liver chemistries occur in up to 60% of COVID-19 patients and are typically mild. COVID-19- associated liver injury may be because of direct viral cytopathic effect, immune-mediated damage, hypoxia, drug-induced liver injury (DILI), or exacerbation of CLD. COVID-19 patients with CLD and who are liver transplant recipients are at risk for severe disease and mortality. COVID-19 precipitated hepatic decompensation in 20-46% of cirrhotic patients. Alcohol consumption and cases of acute alcohol- associated hepatitis increased during the COVID-19 pandemic. Corticosteroids and calcineurin inhibitors are well tolerated to use during COVID-19 but immunomodulators have been associated with mortality. Less than 50% of transplant recipients produce adequate antibody titers after COVID-19 vaccination. SUMMARY COVID-19 patients with CLD should be monitored for liver injury and hepatic decompensation. Patients with CLD and liver transplant recipients should be considered for targeted COVID-19 pharmacotherapeutics and advised vaccination against COVID-19, including a third booster dose. CLD treatments and immunosuppression in liver transplant recipients could generally continue without interruption during COVID-19 infection, with the possible exception of immunomodulators.
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Affiliation(s)
- James Philip Esteban
- Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Lindsay Sobotka
- Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Colmbus, Ohio
| | - Don C Rockey
- Division of Gastroenterology and Hepatology, Medical University of South Carolina, South Carolina, Charleston, USA
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50
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Abstract
With the spread of coronavirus disease 2019 (COVID-19) worldwide, extrapulmonary lesions, including liver dysfunction, have attracted growing attention. The mechanisms underlying liver dysfunction in COVID-19 remain unclear. The reported prevalence of liver dysfunction varies widely across studies. In addition, its impact on clinical outcomes and its recovery after discharge are still controversial. In this review, pathological and laboratory findings were analyzed to reveal the potential mechanisms of COVID-19-induced liver injury from onset to recovery. Four patterns of liver damage were summarized according to the pathological findings, including hypoxemia and shock changes, vascular thrombosis and vascular damage, bile duct damage, and other histological changes. With a strict definition, the prevalence of liver dysfunction was not as high as reported. Meanwhile, liver dysfunction improved during the process of recovery. Nevertheless, the definite liver dysfunction was significantly associated with severe clinical course, which should not be ignored.
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Affiliation(s)
- Wen-Zheng Yuan
- Department of Gastrointestinal Surgery II, Renmin Hospital, Wuhan University, Wuhan, Hubei Province, China
| | - Tao Fu
- Department of Gastrointestinal Surgery II, Renmin Hospital, Wuhan University, Wuhan, Hubei Province, China
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