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Konstantis G, Moghadam DGL, Frey A, Nuruzade N, Schramm C, Gerges C, Lange CM, Schmidt H, Willuweit K, Kahraman A, Passenberg M, Rashidi-Alavijeh J. Prognostic factors for transplant-free survival in patients with secondary sclerosing cholangitis associated with critical illness. BMJ Open Gastroenterol 2025; 12:e001571. [PMID: 39755560 PMCID: PMC11748924 DOI: 10.1136/bmjgast-2024-001571] [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: 08/27/2024] [Accepted: 11/06/2024] [Indexed: 01/06/2025] Open
Abstract
OBJECTIVE Secondary sclerosing cholangitis (SSC) represents a disease with a poor prognosis increasingly diagnosed in clinical settings. Notably, SSC in critically ill patients (SSC-CIP) is the most frequent cause. Variables associated with worse prognosis remain unclear. The primary aim of this study was to identify factors associated with transplant-free survival in SSC-CIP patients using readily available data. METHODS A cohort of 47 patients diagnosed with SSC-CIP was retrospectively analysed for clinical, biochemical and endoscopic variables. Kaplan-Meier survival curves, log-rank tests and univariate Cox proportional hazards models were used to assess associations with transplant-free survival. A multivariable Cox regression model was constructed using Lasso regularisation and validated with Bootstrap resampling. Model performance was assessed using the C-statistic for discrimination. RESULTS Kaplan-Meier analysis identified bile duct obstruction requiring stent placement, and cholangitis episodes, as significant prognostic factors. In univariable analysis, age over 47 years (HR 2.61 (95% CI 1.02, 7.06), p=0.04), at least one cholangitis episode (HR 2.46 (95% CI 1.005, 6.06), p=0.04), stent placement (HR 2.89 (95% CI 1.13, 7.38), p=0.03), lower albumin levels (HR 0.52 (95% CI 0.28, 0.97), p=0.04) and higher international normalised ratio (INR) (HR 3.22 (95% CI 1.09, 9.53), p=0.03) were significant. Multivariable analysis showed that age at diagnosis, albumin and INR were significant independent predictors. The C-index was 0.78 (95% CI 0.65, 0.91), surpassing the model of end-stage liver disease score's prognostic accuracy (Concordance Index at 3 years: 66.2% vs 74.9%). CONCLUSION These findings provide valuable insights for establishing standard exception criteria for this rare liver disease, which could lead to improved organ allocation. Further prospective multicentre studies are necessary to validate our findings.
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Affiliation(s)
| | - Dorsa Ghaffar Loy Moghadam
- Department of Gastroenterology, Hepatology and Transplant Medicine, University of Duisburg-Essen, Essen, Germany
| | - Alexandra Frey
- Department of Gastroenterology, Hepatology and Transplant Medicine, University of Duisburg-Essen, Essen, Germany
| | - Nargiz Nuruzade
- Department of Gastroenterology, Hepatology and Transplant Medicine, University of Duisburg-Essen, Essen, Germany
| | - Christoph Schramm
- Department of Gastroenterology, Hepatology and Transplant Medicine, University of Duisburg-Essen, Essen, Germany
| | - Christian Gerges
- Department of Gastroenterology, Hepatology and Transplant Medicine, University of Duisburg-Essen, Essen, Germany
| | - Christian M Lange
- Department of Gastroenterology, Hepatology and Transplant Medicine, Ludwig-Maximilians-Universität München Medizinische Fakultät, Munchen, Germany
| | - Hartmut Schmidt
- Department of Gastroenterology, Hepatology and Transplant Medicine, University of Duisburg-Essen, Essen, Germany
| | - Katharina Willuweit
- Department of Gastroenterology, Hepatology and Transplant Medicine, University of Duisburg-Essen, Essen, Germany
| | - Alisan Kahraman
- Department of Gastroenterology, Hepatology and Transplant Medicine, Max Grundig Klinik GmbH, Buhl, Germany
| | - Moritz Passenberg
- Department of Gastroenterology, Hepatology and Transplant Medicine, University of Duisburg-Essen, Essen, Germany
| | - Jassin Rashidi-Alavijeh
- Department of Gastroenterology, Hepatology and Transplant Medicine, University of Duisburg-Essen, Essen, Germany
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Khoury NC, Birk JW. A Review of IgG4-related Sclerosing Cholangitis (IgG4-SC). J Clin Gastroenterol 2024; 58:963-969. [PMID: 38385591 DOI: 10.1097/mcg.0000000000001984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/23/2024]
Abstract
IgG4-related sclerosing cholangitis (IgG4-SC) is a unique, steroid-responsive, fibroinflammatory condition that is more commonly found in older men and is strongly associated with autoimmune pancreatitis (AIP). It may pose a diagnostic challenge at times due to closely mimicking hepatobiliary diseases such as primary sclerosing cholangitis (PSC), secondary sclerosing cholangitis (SSC), and cholangiocarcinoma. IgG4-SC has an excellent prognosis when promptly diagnosed and treated with steroids. Literature search strategy: The authors searched PubMed and Google Scholar, for articles with the search terms "autoimmune cholangiopathy" and "IgG4 cholangiopathy."
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Affiliation(s)
- Neil C Khoury
- Division of Gastroenterology and Hepatology, University of Connecticut Health, Farmington, CT
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Guarienti FA, Gonçalves JIB, Gonçalves JB, Antônio Costa Xavier F, Marinowic D, Machado DC. COVID-19: a multi-organ perspective. Front Cell Infect Microbiol 2024; 14:1425547. [PMID: 39492990 PMCID: PMC11527788 DOI: 10.3389/fcimb.2024.1425547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 09/18/2024] [Indexed: 11/05/2024] Open
Abstract
In this mini review, we explore the complex network of inflammatory reactions incited by SARS-CoV-2 infection, which extends its reach well beyond the respiratory domain to influence various organ systems. Synthesizing existing literature, it elucidates how the hyperinflammation observed in COVID-19 patients affects multiple organ systems leading to physiological impairments that can persist over long after the resolution of infection. By exploring the systemic manifestations of this inflammatory cascade, from acute respiratory distress syndrome (ARDS) to renal impairment and neurological sequelae, the review highlights the profound interplay between inflammation and organ dysfunction. By synthesizing recent research and clinical observations, this mini review aims to provide an overview of the systemic interactions and complications associated with COVID-19, underscoring the need for an integrated approach to treatment and management. Understanding these systemic effects is crucial for improving patient outcomes and preparing for future public health challenges.
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Affiliation(s)
- Fabiana Amaral Guarienti
- Graduate Program in Biomedical Gerontology, School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil
- Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil
| | - João Ismael Budelon Gonçalves
- Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil
| | - Júlia Budelon Gonçalves
- Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil
| | - Fernando Antônio Costa Xavier
- Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil
| | - Daniel Marinowic
- Graduate Program in Biomedical Gerontology, School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil
- Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil
| | - Denise Cantarelli Machado
- Graduate Program in Biomedical Gerontology, School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil
- Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil
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4
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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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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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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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8
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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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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: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 03/13/2023] [Indexed: 05/01/2023]
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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Taylor-Robinson SD, Morgan MY. COVID-19 and the Liver: A Complex and Evolving Picture. Hepat Med 2023; 15:209-220. [PMID: 37965296 PMCID: PMC10641025 DOI: 10.2147/hmer.s384172] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 10/28/2023] [Indexed: 11/16/2023] Open
Abstract
Although the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily attacks the respiratory system, other organs, such as the liver, are also affected. In this overview, the effects of SARS-CoV-2 infection on the liver in both healthy people and in those with pre-existing liver disease are documented; the relationship between coronavirus disease 19 (COVID-19) vaccination and liver injury is examined; the mechanism of SARS-CoV-2-associated liver injury is explored; and the long-term consequences of COVID-19 are delineated, both in people with and without pre-existing liver disease.
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Affiliation(s)
- Simon D Taylor-Robinson
- Department of Surgery and Cancer, Imperial College London, London, UK
- Department of Public Health, Busitema University and Mbale Clinical Research Institute, Mbale, Uganda
| | - Marsha Y Morgan
- UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, London, UK
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11
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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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12
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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: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 06/07/2023] [Accepted: 08/23/2023] [Indexed: 09/20/2023] Open
Abstract
BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has had a profound impact on global health, primarily characterized by severe respiratory illness. However, emerging evidence suggests that COVID-19 can also lead to secondary sclerosing cholangitis (SC), referred to as post-COVID-19 cholangiopathy. AIM To synthesize currently reported cases to assess the current state of knowledge on post-COVID-19 cholangiopathy. METHODS Medical Subject Headings and Health Sciences Descriptors were used to retrieve relevant studies, which were combined using Boolean operators. Searches were conducted on electronic databases including Scopus, Web of Science, and MEDLINE (PubMed). Studies published in English, Spanish, or Portuguese were included, with no restrictions on the publication date. Additionally, the reference lists of retrieved studies were manually searched. Simple descriptive analyses were used to summarize the results. Then the data were extracted and assessed based on Reference Citation Analysis (https://www.referencecitationanalysis.com/). RESULTS The initial search yielded a total of 192 articles. After screening, 85 articles were excluded due to duplication, leaving 107 articles for further review. Of these, 63 full-length articles met the inclusion criteria and were included in the analyses. Most of the patients were male and exhibited elevated liver function tests (93.8%). Magnetic resonance imaging revealed duct thickening with contrast enhancement (47.7%), as well as beading of the intrahepatic ducts (45.7%) with peribiliary contrast enhancement on diffusion (28.7%). Liver biopsy results confirmed SC in most cases (74.4%). Sixteen patients underwent liver transplantation, with three experiencing successful outcomes. CONCLUSION Post-COVID-19 cholangiopathy is a serious condition that is expected to become increasingly concerning in the coming years, particularly considering long COVID syndromes. Although liver transplantation has been proposed as a potential treatment option, more research is necessary to establish its efficacy and explore other potential treatments.
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Affiliation(s)
| | | | | | - Jonathan Soldera
- Acute Medicine, University of South Wales, Cardiff CF37 1DL, United Kingdom
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13
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Kondo R, Iwakiri Y, Kage M, Yano H. Endotheliopathy of liver sinusoidal endothelial cells in liver disease. Pathol Int 2023; 73:381-393. [PMID: 37589433 DOI: 10.1111/pin.13361] [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: 07/21/2023] [Accepted: 07/27/2023] [Indexed: 08/18/2023]
Abstract
Liver is the largest solid organ in the abdominal cavity, with sinusoid occupying about half of its volume. Under liver disease, hemodynamics in the liver tissue dynamically change, resulting in injury to liver sinusoidal endothelial cells (LSECs). We discuss the injury of LSECs in liver diseases in this article. Generally, in noninflamed tissues, vascular endothelial cells maintain quiescence of circulating leukocytes, and unnecessary blood clotting is inhibited by multiple antithrombotic factors produced by the endothelial cells. In the setting of inflammation, injured endothelial cells lose these functions, defined as inflammatory endotheliopathy. In chronic hepatitis C, inflammatory endotheliopathy in LSECs contributes to platelet accumulation in the liver tissue, and the improvement of thrombocytopenia by splenectomy is attenuated in cases with severe hepatic inflammation. In COVID-19, LSEC endotheliopathy induced by interleukin (IL)-6 trans-signaling promotes neutrophil accumulation and platelet microthrombosis in the liver sinusoids, resulting in liver injury. IL-6 trans-signaling promotes the expression of intercellular adhesion molecule-1, chemokine (C-X-C motif) ligand (CXCL1), and CXCL2, which are the neutrophil chemotactic mediators, and P-selectin, E-selectin, and von Willebrand factor, which are involved in platelet adhesion to endothelial cells, in LSECs. Restoring LSECs function is important for ameliorating liver injury. Prevention of endotheliopathy is a potential therapeutic strategy in liver disease.
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Affiliation(s)
- Reiichiro Kondo
- Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan
| | - Yasuko Iwakiri
- Section of Digestive Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Masayoshi Kage
- Department of Medical Engineering, Junshin Gakuen University, Fukuoka, Japan
| | - Hirohisa Yano
- Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan
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14
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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: 1] [Impact Index Per Article: 0.5] [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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15
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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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16
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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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17
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Pizarro Vega NM, Valer Lopez-Fando P, de la Poza Gómez G, Piqueras Alcol B, Gil Santana M, Ruiz Fuentes P, Rodríguez Amado MA, Bermejo San José F. Secondary sclerosing cholangitis: A complication after severe COVID-19 infection. GASTROENTEROLOGIA Y HEPATOLOGIA 2023; 46:462-466. [PMID: 35569544 PMCID: PMC9188449 DOI: 10.1016/j.gastrohep.2022.04.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 03/14/2022] [Accepted: 04/05/2022] [Indexed: 11/30/2022]
Affiliation(s)
| | - Paz Valer Lopez-Fando
- Departamento de Gastroenterología, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, España
| | - Gema de la Poza Gómez
- Departamento de Gastroenterología, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, España
| | - Belén Piqueras Alcol
- Departamento de Gastroenterología, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, España
| | - Marina Gil Santana
- Departamento de Gastroenterología, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, España
| | - Paloma Ruiz Fuentes
- Departamento de Gastroenterología, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, España
| | | | - Fernando Bermejo San José
- Departamento de Gastroenterología, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, España
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18
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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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19
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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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20
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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
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21
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Möller K, Braden B, Culver EL, Jenssen C, Zadeh ES, Alhyari A, Görg C, Ignee A, Hocke M, Dong Y, Sun S, Faiss S, Dietrich CF. Secondary sclerosing cholangitis and IgG4-sclerosing cholangitis - A review of cholangiographic and ultrasound imaging. Endosc Ultrasound 2023; 12:181-199. [PMID: 36588352 PMCID: PMC10237613 DOI: 10.4103/eus-d-22-00208] [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: 11/20/2022] [Accepted: 12/08/2022] [Indexed: 01/01/2023] Open
Abstract
Sclerosing cholangitis (SC) represents a spectrum of chronic progressive cholestatic diseases of the intrahepatic and/or extrahepatic biliary system characterized by patchy inflammation, fibrosis, and stricturing. Primary and secondary SC must be distinguished given the different treatment modalities, risks of malignancy, and progression to portal hypertension, cirrhosis, and hepatic failure. This review focuses on secondary SC and the pathogenic mechanisms, risk factors, clinical presentation, and novel imaging modalities that help to distinguish between these conditions. We explore the detailed use of cholangiography and ultrasound imaging techniques.
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Affiliation(s)
- Kathleen Möller
- Medical Department I/Gastroenterology, Sana Hospital Lichtenberg, Berlin, Germany
| | - Barbara Braden
- Translational Gastroenterology Unit, Oxford University Hospitals, Oxford, UK
| | - Emma L. Culver
- Translational Gastroenterology Unit, Oxford University Hospitals, Oxford, UK
| | - Christian Jenssen
- Department of Internal Medicine, Krankenhaus Märkisch Oderland GmbH, Strausberg, Wriezen, Germany
- Brandenburg Institute of Clinical Medicine at Medical University Brandenburg, Neuruppin, Germany
| | - Ehsan Safai Zadeh
- Interdisciplinary Center of Ultrasound Diagnostics, University Hospital Giessen and Marburg, Philipps University Marburg, Marburg, Germany
| | - Amjad Alhyari
- Interdisciplinary Center of Ultrasound Diagnostics, University Hospital Giessen and Marburg, Philipps University Marburg, Marburg, Germany
| | - Christian Görg
- Interdisciplinary Center of Ultrasound Diagnostics, University Hospital Giessen and Marburg, Philipps University Marburg, Marburg, Germany
| | - André Ignee
- Department of Internal Medicine – Gastroenterology and Rheumatology; Klinikum Wuerzburg Mitte, Wuerzburg, Germany
| | - Michael Hocke
- Medical Department II, Helios Klinikum Meiningen, Meiningen, Germany
| | - Yi Dong
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Siyu Sun
- Department of Endoscopy Center, Shengjing Hospital of China Medical University, Liaoning Province, China
| | - Siegbert Faiss
- Medical Department I/Gastroenterology, Sana Hospital Lichtenberg, Berlin, Germany
| | - Christoph F. Dietrich
- Department of Internal Medicine (DAIM), Hirslanden Private Hospital, Beau Site, Salem und Permanence, Bern, Switzerland
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22
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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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23
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Boraschi P, Donati F, Ambrosini I, Bruni L, Mazzeo ML, Tintori R, Tonerini M, Neri E. Diagnostic and Therapeutic Radiology of the GI Tract, Liver, and Pancreas in Patients with COVID. Gastroenterol Clin North Am 2023; 52:185-200. [PMID: 36813425 PMCID: PMC9626443 DOI: 10.1016/j.gtc.2022.10.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Coronavirus disease 2019 (COVID-19) pulmonary involvement has been extensively reported in the literature. Current data highlight how COVID-19 is a systemic disease, affecting many other organs, including the gastrointestinal, hepatobiliary, and pancreatic organs. Recently, these organs have been investigated using imaging modalities of ultrasound and particularly computed tomography. Radiological findings of the gastrointestinal, hepatic, and pancreatic involvement in patients with COVID-19 are generally nonspecific but are nonetheless helpful to evaluate and manage COVID-19 patients with involvement of these organs.
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Affiliation(s)
- Piero Boraschi
- 2nd Unit of Radiology, Department of Diagnostic and Interventional Radiology, and Nuclear Medicine, Pisa University Hospital, Via Paradisa 2, Pisa 56124, Italy.
| | - Francescamaria Donati
- 2nd Unit of Radiology, Department of Diagnostic and Interventional Radiology, and Nuclear Medicine, Pisa University Hospital, Via Paradisa 2, Pisa 56124, Italy
| | - Ilaria Ambrosini
- Academic Radiology, Department of Translational Research, University of Pisa, Via Roma 67, Pisa 56126, Italy
| | - Luciana Bruni
- Academic Radiology, Department of Translational Research, University of Pisa, Via Roma 67, Pisa 56126, Italy
| | - Maria Letizia Mazzeo
- Academic Radiology, Department of Translational Research, University of Pisa, Via Roma 67, Pisa 56126, Italy
| | - Rachele Tintori
- 2nd Unit of Radiology, Department of Diagnostic and Interventional Radiology, and Nuclear Medicine, Pisa University Hospital, Via Paradisa 2, Pisa 56124, Italy
| | - Michele Tonerini
- Unit of Emergency Radiology, Department of Surgical, Medical, Molecular and Critical Area Pathology, Pisa University Hospital, Via Paradisa 2, Pisa 56124, Italy
| | - Emanuele Neri
- Academic Radiology, Department of Translational Research, University of Pisa, Via Roma 67, Pisa 56126, Italy
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24
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Ekpanyapong S, Reddy KR. Liver and Biliary Tract Disease in Patients with Coronavirus disease-2019 Infection. Gastroenterol Clin North Am 2023; 52:13-36. [PMID: 36813421 PMCID: PMC9531659 DOI: 10.1016/j.gtc.2022.09.001] [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] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Coronavirus disease-2019 (COVID-19) had become a global pandemic since March 2020. Although, the most common presentation is of pulmonary involvement, hepatic abnormalities can be encountered in up to 50% of infected individuals, which may be associated with disease severity, and the mechanism of liver injury is thought to be multifactorial. Guidelines for management in patients with chronic liver disease during COVID-19 era are being regularly updated. Patients with chronic liver disease and cirrhosis, including liver transplant candidates and liver transplant recipients are strongly recommended to receive SARS-CoV-2 vaccination because it can reduce rate of COVID-19 infection, COVID-19-related hospitalization, and mortality.
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Affiliation(s)
- Sirina Ekpanyapong
- Division of Gastroenterology and Hepatology, Department of Medicine, Huachiew General Hospital, 665 Bumroongmueang Road, Khlong Mahanak, Bangkok 10100, Thailand; Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, 2 Dulles, Liver Transplant Office, HUP3400 Spruce Street, Philadelphia, PA 19104, USA
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, 2 Dulles, Liver Transplant Office, HUP3400 Spruce Street, Philadelphia, PA 19104, USA.
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25
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Heubner L, Trautmann-Grill K, Tiebel O, Mirus M, Güldner A, Rand A, Spieth PM. Treatment of Acquired von Willebrand Disease due to Extracorporeal Membrane Oxygenation in a Pediatric COVID-19 Patient with Vonicog Alfa: A Case Report and Literature Review. TH OPEN 2023; 7:e76-e81. [PMID: 36846831 PMCID: PMC9949976 DOI: 10.1055/a-2008-4367] [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: 08/29/2022] [Accepted: 01/02/2023] [Indexed: 01/07/2023] Open
Abstract
Acquired von Willebrand disease (aVWD) is frequently observed in patients with the need for extracorporeal membrane oxygenation (ECMO). aVWD can be treated by plasma-derived concentrates containing factor VIII (FVIII) and/or von Willebrand factor (VWF) and recombinant VWF concentrate as well as adjuvant therapies such as tranexamic acid and desmopressin. However, all of these therapeutic options possibly cause thromboembolism. Therefore, the optimal treatment remains uncertain. This report presents a case of a 16-year-old patient suffering from severe acute respiratory distress syndrome due to coronavirus disease 2019 with the need of ECMO support. Our patient developed aVWD under ECMO therapy characterized by loss of high-molecular-weight multimers (HMWM) and severe bleeding symptoms following endoscopic papillotomy due to sclerosing cholangitis. At the same time standard laboratory parameters showed hypercoagulability with increased fibrinogen level and platelet count. The patient was successfully treated with recombinant VWF concentrate (rVWF; vonicog alfa; Veyvondi) combined with topic tranexamic acid application and cortisone therapy. rVWF concentrate vonicog alfa is characterized by ultra-large multimers and absence of FVIII. Patient could be successfully weaned from ECMO support after 72 days. Multimer analysis 1 week after ECMO decannulation showed an adequate reappearance of HMWM.
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Affiliation(s)
- Lars Heubner
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany,Address for correspondence Lars Heubner, MD Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus DresdenDresdenGermany
| | - Karolin Trautmann-Grill
- Department of Internal Medicine I, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden. Germany
| | - Oliver Tiebel
- Institute of Clinical Chemistry, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden. Germany
| | - Martin Mirus
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany
| | - Andreas Güldner
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany
| | - Axel Rand
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany
| | - Peter Markus Spieth
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany
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26
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Gildea DT, Woo SM, O’Connor CE, Rangnekar AS. COVID-19-Associated Liver Injury. Hepat Med 2023; 15:1-9. [PMID: 36852138 PMCID: PMC9960793 DOI: 10.2147/hmer.s384108] [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: 12/20/2022] [Accepted: 02/11/2023] [Indexed: 03/01/2023] Open
Abstract
This review analyzes data regarding liver injury associated with COVID-19 infection. We discuss reported effects on the liver from both COVID-19 and COVID-19 treatment as well as pathophysiology, review the potential role of drug-induced liver injury as an etiology of COVID-19-associated liver injury, and touch on other reports of significant outcomes including COVID-19 cholangiopathy and autoimmune hepatitis. Finally, we review the implications of COVID-19 infection in liver transplant recipients.
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Affiliation(s)
- Daniel T Gildea
- Department of Internal Medicine, MedStar Georgetown University Hospital, Washington, DC, USA,Correspondence: Daniel T Gildea, Tel +1 302-985-7777, Email
| | - Stephanie M Woo
- Department of Gastroenterology, MedStar Georgetown University Hospital, Washington, DC, USA
| | | | - Amol S Rangnekar
- MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Washington, DC, USA
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27
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Ippolito D, Maino C, Vernuccio F, Cannella R, Inchingolo R, Dezio M, Faletti R, Bonaffini PA, Gatti M, Sironi S. Liver involvement in patients with COVID-19 infection: A comprehensive overview of diagnostic imaging features. World J Gastroenterol 2023; 29:834-850. [PMID: 36816623 PMCID: PMC9932422 DOI: 10.3748/wjg.v29.i5.834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 12/06/2022] [Accepted: 01/20/2023] [Indexed: 02/06/2023] Open
Abstract
During the first wave of the pandemic, coronavirus disease 2019 (COVID-19) infection has been considered mainly as a pulmonary infection. However, different clinical and radiological manifestations were observed over time, including involvement of abdominal organs. Nowadays, the liver is considered one of the main affected abdominal organs. Hepatic involvement may be caused by either a direct damage by the virus or an indirect damage related to COVID-19 induced thrombosis or to the use of different drugs. After clinical assessment, radiology plays a key role in the evaluation of liver involvement. Ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI) may be used to evaluate liver involvement. US is widely available and it is considered the first-line technique to assess liver involvement in COVID-19 infection, in particular liver steatosis and portal-vein thrombosis. CT and MRI are used as second- and third-line techniques, respectively, considering their higher sensitivity and specificity compared to US for assessment of both parenchyma and vascularization. This review aims to the spectrum of COVID-19 liver involvement and the most common imaging features of COVID-19 liver damage.
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Affiliation(s)
- Davide Ippolito
- Milano Bicocca School of Medicine and Surgery, Milano 20126, Italy
- Fondazione IRCCS San Gerardo dei Tintori, Monza 20900, Italy
| | - Cesare Maino
- Fondazione IRCCS San Gerardo dei Tintori, Monza 20900, Italy
| | - Federica Vernuccio
- Institute of Radiology (DIMED), University Hospital of Padova, Padova 35128, Italy
| | - Roberto Cannella
- Section of Radiology-Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, Palermo 90127, Italy
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo 90127, Italy
| | - Riccardo Inchingolo
- Division of Interventional Radiology, Department of Radiology, Madonna delle Grazie Hospital, Matera 75100, Italy
| | - Michele Dezio
- Division of Interventional Radiology, Department of Radiology, Madonna delle Grazie Hospital, Matera 75100, Italy
| | - Riccardo Faletti
- Department of Surgical Sciences, University of Turin, Turin 10126, Italy
| | - Pietro Andrea Bonaffini
- Milano Bicocca School of Medicine and Surgery, Milano 20126, Italy
- Department of Diagnostic Radiology, Papa Giovanni XXIII Hospital, Bergamo 24127, Italy
| | - Marco Gatti
- Department of Diagnostic Radiology, University of Turin, Turin 10126, Italy
| | - Sandro Sironi
- Milano Bicocca School of Medicine and Surgery, Milano 20126, Italy
- Department of Diagnostic Radiology, Papa Giovanni XXIII Hospital, Bergamo 24127, Italy
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28
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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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29
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Valsamaki A, Xanthoudaki M, Oikonomou KG, Vlachostergios PJ, Papadogoulas A, Katsiafylloudis P, Voulgaridi I, Skoura AL, Komnos A, Papamichalis P. Prevention, diagnostic evaluation, management and prognostic implications of liver disease in critically ill patients with COVID-19. World J Clin Cases 2023; 11:514-527. [PMID: 36793637 PMCID: PMC9923862 DOI: 10.12998/wjcc.v11.i3.514] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 12/05/2022] [Accepted: 01/10/2023] [Indexed: 01/23/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, broke out in December 2019 in Wuhan city of China and spread rapidly worldwide. Therefore, by March 2020, the World Health Organization declared the disease a global pandemic. Apart from the respiratory system, various other organs of the human body are also seriously affected by the virus. Liver injury in patients with a severe form of COVID-19 is estimated to be 14.8%-53.0%. Elevated levels of total bilirubin, aspartate aminotransferase and alanine aminotransferase and low levels of serum albumin and prealbumin are the main laboratory findings. Patients with pre-existing chronic liver disease and cirrhosis are much more prone to develop severe liver injury. This literature review presented the recent scientific findings regarding the pathophysiological mechanisms responsible for liver injury in critically ill patients with COVID-19, the various interactions between drugs used to treat the disease and the function of the liver and the specific tests providing the possibility of early diagnosis of severe liver injury in these patients. Moreover, it highlighted the burden that COVID-19 put on health systems worldwide and its effect on transplant programs and the care provided to critically ill patients in general and particularly to those with chronic liver disease.
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Affiliation(s)
- Asimina Valsamaki
- Intensive Care Unit, General Hospital of Larissa, Larissa 41221, Greece
| | - Maria Xanthoudaki
- Intensive Care Unit, General Hospital of Larissa, Larissa 41221, Greece
| | | | - Panagiotis J Vlachostergios
- Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, United States
| | | | | | - Ioanna Voulgaridi
- Department of Microbiology, General Hospital of Larissa, Larissa 41221, Greece
| | | | - Apostolos Komnos
- Intensive Care Unit, General Hospital of Larissa, Larissa 41221, Greece
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30
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Valsamaki A, Xanthoudaki M, Oikonomou KG, Vlachostergios PJ, Papadogoulas A, Katsiafylloudis P, Voulgaridi I, Skoura AL, Komnos A, Papamichalis P. Prevention, diagnostic evaluation, management and prognostic implications of liver disease in critically ill patients with COVID-19. World J Clin Cases 2023; 11:514-527. [DOI: 18.valsamaki a, xanthoudaki m, oikonomou kg, vlachostergios pj, papadogoulas a, katsiafylloudis p, voulgaridi i, skoura al, komnos a, papamichalis p.prevention, diagnostic evaluation, management and prognostic implications of liver disease in critically ill patients with covid-19.world j clin cases.2023 jan 26;11(3):514-527.doi: 10.12998/wjcc.v11.i3.514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/17/2025] Open
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31
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Baldelli L, Marjot T, Barnes E, Barritt AS, Webb GJ, Moon AM. SARS-CoV-2 Infection and Liver Disease: A Review of Pathogenesis and Outcomes. Gut Liver 2023; 17:12-23. [PMID: 36457261 PMCID: PMC9840920 DOI: 10.5009/gnl220327] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/31/2022] [Accepted: 09/07/2022] [Indexed: 12/03/2022] Open
Abstract
The impact of the coronavirus disease 2019 (COVID-19) pandemic has been immense, and it continues to have lasting repercussions. While the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus primarily infects the respiratory system, other organ systems are affected, including the liver. Scientific knowledge on the role of SARS-CoV-2 infection and liver injury has evolved rapidly, with recent data suggesting specific hepatotropism of SARS-CoV-2. Moreover, additional concerns have been raised in regard to long-term liver damage, related to emerging cases of post-COVID-19 cholangiopathy and chronic cholestasis. Great effort has also been focused on studying how specific subpopulations with chronic medical conditions might be disproportionately impacted by COVID-19. One such population includes individuals with chronic liver disease (CLD) and cirrhosis, with an expanding body of research indicating these patients being particularly susceptible to adverse outcomes. In this review, we provide an updated summary on the current pathogenesis and mechanism of liver injury in the setting of SARS-CoV-2 infection, the association between health outcomes and SARS-CoV-2 infection in patients with CLD, and the unique consequences of the COVID-19 pandemic on the routine care of patients with CLD.
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Affiliation(s)
- Luke Baldelli
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
| | - Thomas Marjot
- Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, UK
| | - Eleanor Barnes
- Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, UK
| | - A. Sidney Barritt
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
| | - Gwilym J. Webb
- Cambridge Liver Unit, Addenbrooke's Hospital, Cambridge, UK
| | - Andrew M. Moon
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
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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: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 10/13/2022] [Accepted: 11/23/2022] [Indexed: 01/11/2023] Open
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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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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Nowroozi A, Momtazmanesh S, Rezaei N. COVID-19 and MAFLD/NAFLD: An updated review. Front Med (Lausanne) 2023; 10:1126491. [PMID: 37035343 PMCID: PMC10080090 DOI: 10.3389/fmed.2023.1126491] [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: 02/08/2023] [Accepted: 03/10/2023] [Indexed: 04/11/2023] Open
Abstract
The COVID-19 pandemic is ongoing and places a substantial burden on healthcare systems worldwide. As we further shed light on different disease characteristics, we identify more and more groups of people at higher risk of poor COVID-19 outcomes. Metabolic-associated fatty liver disease (MAFLD) (previously non-alcoholic fatty liver disease or NAFLD) is a common metabolic disorder characterized by fat accumulation and liver fibrosis. Given its close correlation with metabolic syndrome, an established risk factor for severe COVID-19, it is necessary to investigate its interplay with the novel coronavirus. In this study, we review the available data on COVID-19 prognosis, treatment and prevention options in patients with MAFLD, and the effect that the disease and the pandemic have on MAFLD care. Furthermore, we point out the gaps in the current literature to accentuate the work that needs to be done to improve MAFLD care during the pandemic and beyond.
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Affiliation(s)
- Ali Nowroozi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Sara Momtazmanesh
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- *Correspondence: Sara Momtazmanesh,
| | - Nima Rezaei
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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Bucurica S, Ionita Radu F, Bucurica A, Socol C, Prodan I, Tudor I, Sirbu CA, Plesa FC, Jinga M. Risk of New-Onset Liver Injuries Due to COVID-19 in Preexisting Hepatic Conditions-Review of the Literature. MEDICINA (KAUNAS, LITHUANIA) 2022; 59:medicina59010062. [PMID: 36676691 PMCID: PMC9864905 DOI: 10.3390/medicina59010062] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 12/21/2022] [Accepted: 12/23/2022] [Indexed: 12/29/2022]
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted the world and caused the 2019 coronavirus disease (COVID-19) pandemic. The clinical manifestations of the virus can vary from patient to patient, depending on their respective immune system and comorbidities. SARS-CoV-2 can affect patients through two mechanisms: directly by targeting specific receptors or by systemic mechanisms. We reviewed data in the latest literature in order to discuss and determine the risk of new-onset liver injuries due to COVID-19 in preexisting hepatic conditions. The particular expression of angiotensin-converting enzyme 2 (ACE2) receptors is an additional risk factor for patients with liver disease. COVID-19 causes more severe forms in patients with non-alcoholic fatty liver disease (NAFLD), increases the risk of cirrhosis decompensation, and doubles the mortality for these patients. The coinfection SARS-CoV-2-viral hepatitis B or C might have different outcomes depending on the stage of the liver disease. Furthermore, the immunosuppressant treatment administered for COVID-19 might reactivate the hepatic virus. The high affinity of SARS-CoV-2 spike proteins for cholangiocytes results in a particular type of secondary sclerosing cholangitis. The impact of COVID-19 infection on chronic liver disease patients is significant, especially in cirrhosis, influencing the prognosis and outcome of these patients.
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Affiliation(s)
- Sandica Bucurica
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Gastroenterology, ‘Dr. Carol Davila’ Central Military Emergency University Hospital, 010242 Bucharest, Romania
| | - Florentina Ionita Radu
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Gastroenterology, ‘Dr. Carol Davila’ Central Military Emergency University Hospital, 010242 Bucharest, Romania
- Correspondence: (F.I.R.); (F.C.P.)
| | - Ana Bucurica
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Calin Socol
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Ioana Prodan
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Gastroenterology, ‘Dr. Carol Davila’ Central Military Emergency University Hospital, 010242 Bucharest, Romania
| | - Ioana Tudor
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Gastroenterology, ‘Dr. Carol Davila’ Central Military Emergency University Hospital, 010242 Bucharest, Romania
| | - Carmen Adella Sirbu
- Department of Neurology, ‘Dr. Carol Davila’ Central Military Emergency University Hospital, 010242 Bucharest, Romania
- Centre for Cognitive Research in Neuropsychiatric Pathology (Neuropsy-Cog), Department of Neurology, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania
| | - Florentina Cristina Plesa
- Department of Neurology, ‘Dr. Carol Davila’ Central Military Emergency University Hospital, 010242 Bucharest, Romania
- Department of Preclinical Disciplines, Titu Maiorescu University of Medicine, 031593 Bucharest, Romania
- Correspondence: (F.I.R.); (F.C.P.)
| | - Mariana Jinga
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Gastroenterology, ‘Dr. Carol Davila’ Central Military Emergency University Hospital, 010242 Bucharest, Romania
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Polyzogopoulou E, Amoiridou P, Abraham TP, Ventoulis I. Acute liver injury in COVID-19 patients hospitalized in the intensive care unit: Narrative review. World J Gastroenterol 2022; 28:6662-6688. [PMID: 36620339 PMCID: PMC9813941 DOI: 10.3748/wjg.v28.i47.6662] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 11/14/2022] [Accepted: 12/05/2022] [Indexed: 12/19/2022] Open
Abstract
In recent years, humanity has been confronted with a global pandemic due to coronavirus disease 2019 (COVID-19), which has caused an unprecedented health and economic crisis worldwide. Apart from the respiratory symptoms, which are considered the principal manifestations of COVID-19, it has been recognized that COVID-19 constitutes a systemic inflammatory process affecting multiple organ systems. Across the spectrum of organ involvement in COVID-19, acute liver injury (ALI) has been gradually gaining increasing attention by the international scientific community. COVID-19 associated liver impairment can affect a considerable proportion of COVID-19 patients and seems to correlate with the severity of the disease course. Indeed, COVID-19 patients hospitalized in the intensive care unit (ICU) run a greater risk of developing ALI due to the severity of their clinical condition and in the context of multi-organ failure. The putative pathophysiological mechanisms of COVID-19 induced ALI in ICU patients remain poorly understood and appear to be multifactorial in nature. Several theories have been proposed to explain the occurrence of ALI in the ICU setting, such as hypoperfusion and ischemia due to hemodynamic instability, passive liver congestion as a result of congestive heart failure, ischemia-reperfusion injury, hypoxia due to respiratory failure, mechanical ventilation itself, sepsis and septic shock, cytokine storm, endotheliitis with concomitant coagulopathy, drug-induced liver injury, parenteral nutrition and direct cytopathic viral effect. It should be noted that no specific therapy for COVID-19 induced ALI exists. Therefore, the therapeutic approach lies in preventive measures and is exclusively supportive once ALI ensues. The aim of the current review is to scrutinize the existing evidence on COVID-19 associated ALI in ICU patients, explore its clinical implications, shed light on the underlying pathophysiological mechanisms and propose potential therapeutic approaches. Ongoing research on the particular scientific field will further elucidate the pathophysiology behind ALI and address unresolved issues, in the hope of mitigating the tremendous health consequences imposed by COVID-19 on ICU patients.
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Affiliation(s)
- Effie Polyzogopoulou
- Department of Emergency Medicine, Attikon University Hospital, National and Kapodistrian University of Athens Medical School, Athens 12462, Greece
| | - Pinelopi Amoiridou
- Department of Intensive Care, AHEPA University Hospital, Thessaloniki 54621, Greece
| | - Theodore P Abraham
- Hypertrophic Cardiomyopathy Center of Excellence, University of California, San Francisco, CA 94117, United States
| | - Ioannis Ventoulis
- Department of Occupational Therapy, University of Western Macedonia, Ptolemaida 50200, Greece
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Choaib A, Issa E, El Choueiry F, Eldin JN, Shbaklo K, Alhajj M, Sawaya RT, Assi G, Nader M, Chatila R, Faour WH. SARS-CoV-2-mediated liver injury: pathophysiology and mechanisms of disease. Inflamm Res 2022; 72:301-312. [PMID: 36539655 PMCID: PMC9767399 DOI: 10.1007/s00011-022-01683-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 12/13/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND SARS-CoV-2-induced severe inflammatory response can be associated with severe medical consequences leading to multi-organ failure, including the liver. The main mechanism behind this assault is the aggressive cytokine storm that induces cytotoxicity in various organs. Of interest, hepatic stellate cells (HSC) respond acutely to liver injury through several molecular mechanisms, hence furthering the perpetuation of the cytokine storm and its resultant tissue damage. In addition, hepatocytes undergo apoptosis or necrosis resulting in the release of pro-inflammatory and pro-fibrogenic mediators that lead to chronic liver inflammation. AIMS The aim of this review is to summarize available data on SARS-CoV-2-induced liver inflammation in addition to evaluate the potential effect of anti-inflammatory drugs in attenuating SARS-CoV-2-induced liver inflammation. METHODS Thorough PubMed search was done to gather and summarize published data on SARS-CoV-2-induced liver inflammation. Additionally, various anti-inflammatory potential treatments were also documented. RESULTS Published data documented SARS-CoV-2 infection of liver tissues and is prominent in most liver cells. Also, histological analysis showed various features of tissues damage, e.g., hepatocellular necrosis, mitosis, cellular infiltration, and fatty degeneration in addition to microvesicular steatosis and inflammation. Finally, the efficacy of the different drugs used to treat SARS-CoV-2-induced liver injury, in particular the anti-inflammatory remedies, are likely to have some beneficial effect to treat liver injury in COVID-19. CONCLUSION SARS-CoV-2-induced liver inflammation is a serious condition, and drugs with potent anti-inflammatory effect can play a major role in preventing irreversible liver damage in COVID-19.
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Affiliation(s)
- Ali Choaib
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Elio Issa
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Francesca El Choueiry
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Jade Nasser Eldin
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Khodor Shbaklo
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Maryline Alhajj
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Ramy Touma Sawaya
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Ghaith Assi
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Moni Nader
- Department of Physiology and Immunology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, P.O. Box 127788, Abu Dhabi, United Arab Emirates
- Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
| | - Rajaa Chatila
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
- Internal Medicine-Gastroenterology, Lebanese American University Medical Center-Rizk Hospital (LAUMC-RH), Beirut, Lebanon
| | - Wissam H Faour
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon.
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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: 55] [Impact Index Per Article: 18.3] [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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Heucke N, Keitel V. COVID-19-associated cholangiopathy: What is left after the virus has gone? Hepatology 2022; 76:1560-1562. [PMID: 35822670 PMCID: PMC9350171 DOI: 10.1002/hep.32668] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 07/01/2022] [Indexed: 12/08/2022]
Affiliation(s)
- Niklas Heucke
- Department of Gastroenterology, Hepatology and Infectious DiseasesUniversity Hospital Magdeburg, Medical Faculty of Otto von Guericke UniversityMagdeburgGermany
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Mihai N, Lazar M, Tiliscan C, Barbu EC, Chitu CE, Stratan L, Ganea OA, Arama SS, Ion DA, Arama V. Predictors of Liver Injury in Hospitalized Patients with SARS-CoV-2 Infection. Medicina (B Aires) 2022; 58:medicina58121714. [PMID: 36556915 PMCID: PMC9786677 DOI: 10.3390/medicina58121714] [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: 10/12/2022] [Revised: 11/15/2022] [Accepted: 11/21/2022] [Indexed: 11/24/2022] Open
Abstract
Background and Objectives: SARS-CoV-2 infection is frequently associated with pneumonia but has a broad tissue tropism also leading to systemic complications (hematologic, gastro-intestinal, cardiac, neurologic, etc.). In this study, we aim to evaluate the impact of COVID-19 infection on the liver and to identify the risk factors/predictors for liver injury at admission to the hospital. Materials and Methods: We performed a retrospective cohort study on 249 patients, divided into two Group A (157 patients with liver involvement) and Group B (92 patients without liver involvement). We recorded demographic and lifestyle parameters, anthropometric parameters, comorbidities, clinical parameters, inflammation markers, complete blood count, coagulation, and biochemical parameters. Lung parenchyma, liver dimensions, and morphology were evaluated by computer tomography (CT) scans. Results: Patients with liver involvement had higher heart and respiratory rates, lower oxygen saturation (SO2), and necessitated higher oxygen flow at admittance. We found higher serum levels of C-reactive protein, fibrinogen, ferritin, creatine kinase, lactate dehydrogenase (LDH), serum triglycerides, and lower values for serum albumin in Group A patients. The patients with liver involvement presented more extensive lung injury with higher percentages of alveolar, mixed, and interstitial lesions, an increase in liver dimensions, and lower density ranges for the liver parenchyma. The patients presented hepatocytolytic involvement in 26 cases (10.4% from the entire study population), cholestatic involvement in 63 cases (37.7% from the entire study population), and mixed liver involvement in 68 cases (37.7% from the entire study population). Conclusions: Liver involvement in COVID-19 patients is frequent, usually mild, and occurs mostly in male patients over 50 years old. Cholestatic and mixed liver injuries are more frequent than hepatocytolytic injuries. The severity of lung injury evaluated by CT scan, increased values of inflammatory markers, LDH, and low values of SO2 can be considered risk factors/predictors for liver injury at admission to the hospital.
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Affiliation(s)
- Nicoleta Mihai
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania
- “Prof. Dr. Matei Bals” National Institute for Infectious Diseases, 1 Dr. Grozovici Street, 021105 Bucharest, Romania
| | - Mihai Lazar
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania
- “Prof. Dr. Matei Bals” National Institute for Infectious Diseases, 1 Dr. Grozovici Street, 021105 Bucharest, Romania
- Correspondence: (M.L.); (C.T.)
| | - Catalin Tiliscan
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania
- “Prof. Dr. Matei Bals” National Institute for Infectious Diseases, 1 Dr. Grozovici Street, 021105 Bucharest, Romania
- Correspondence: (M.L.); (C.T.)
| | - Ecaterina Constanta Barbu
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania
| | - Cristina Emilia Chitu
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania
| | - Laurentiu Stratan
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania
| | - Oana Alexandra Ganea
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania
- “Prof. Dr. Matei Bals” National Institute for Infectious Diseases, 1 Dr. Grozovici Street, 021105 Bucharest, Romania
| | - Sorin Stefan Arama
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania
| | - Daniela Adriana Ion
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania
| | - Victoria Arama
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania
- “Prof. Dr. Matei Bals” National Institute for Infectious Diseases, 1 Dr. Grozovici Street, 021105 Bucharest, Romania
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Kulkarni AV, Khelgi A, Sekaran A, Reddy R, Sharma M, Tirumalle S, Gora BA, Somireddy A, Reddy J, Menon B, Reddy DN, Rao NP. Post-COVID-19 Cholestasis: A Case Series and Review of Literature. J Clin Exp Hepatol 2022; 12:1580-1590. [PMID: 35719861 PMCID: PMC9187855 DOI: 10.1016/j.jceh.2022.06.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 06/06/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Coronavirus disease-2019 (COVID-19) cholangiopathy is a recently known entity. There are very few reports of liver transplantation (LT) for COVID-19-induced cholangiopathy. It is well known that vaccines can prevent severe disease and improve outcomes. However, there are no reports on the impact of COVID-19 vaccines on cholestasis. Therefore, we aimed to compare the course and outcome of patients who developed cholestasis following COVID-19 infection among vaccinated and unvaccinated individuals. Methods: Patients diagnosed with post-COVID cholestasis during the pandemic were included in the study after excluding other causes of cholestasis. RESULTS Eight unvaccinated and seven vaccinated individuals developed cholestasis following COVID-19 infection. Baseline demographics, presentation, severity, and management of COVID-19 were similar in both groups. However, patients in the unvaccinated group had a protracted course. The peak ALP was 312 (239-517) U/L in the vaccinated group and 571.5 (368-1058) U/L in the unvaccinated group (P = 0.02). Similarly, the peak γ-glutamyl transpeptidase values were lower in the vaccinated (325 [237-600] U/L) than in the unvaccinated group (832 [491-1640] U/L; P = 0.004). However, the peak values of total bilirubin, transaminases, and INR were similar in both groups. Five patients developed ascites gradually in the unvaccinated group whereas none in the vaccinated group developed ascites. Plasma exchange was done in five patients, and two were successfully bridged to living donor LT in the unvaccinated group. Only two patients recovered with conservative management in the unvaccinated group, whereas all recovered with conservative management in the vaccinated group. The other four patients in the unvaccinated group were planned for LT. CONCLUSION Post-COVID-19 cholestasis is associated with high morbidity and mortality, meriting early identification and appropriate management. Vaccination can modify the course of severe COVID-19 infection and improve outcomes.
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Key Words
- ALP, alkaline phosphatase
- ALT, alanine transaminase
- AST, aspartate transaminase
- COVID-19, coronavirus disease-2019
- DDLT, deceased donor living transplantation
- GGT, γ-glutamyl transpeptidase
- LDLT, living donor liver transplantation
- SARS-CoV-2, severe acute respiratory syndrome coronavirus 2
- UDCA, ursodeoxycholic acid
- ULN, upper limit of normal
- liver function test
- liver transplantation
- plasma exchange
- vaccination
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Affiliation(s)
| | - Amit Khelgi
- Department of Microbiology, K S Hegde Medical Academy, Mangalore, India
| | | | - Raghuram Reddy
- Department of Liver Transplantation, AIG Hospitals, Hyderabad, India
| | - Mithun Sharma
- Department of Hepatology, AIG Hospitals, Hyderabad, India
| | | | - Baqar A. Gora
- Department of Hepatology, AIG Hospitals, Hyderabad, India
| | | | - Jignesh Reddy
- Department of Radiology, AIG Hospitals, Hyderabad, India
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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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Impact of COVID-19 on the liver and on the care of patients with chronic liver disease, hepatobiliary cancer, and liver transplantation: An updated EASL position paper. J Hepatol 2022; 77:1161-1197. [PMID: 35868584 PMCID: PMC9296253 DOI: 10.1016/j.jhep.2022.07.008] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 07/06/2022] [Accepted: 07/06/2022] [Indexed: 02/06/2023]
Abstract
The COVID-19 pandemic has presented a serious challenge to the hepatology community, particularly healthcare professionals and patients. While the rapid development of safe and effective vaccines and treatments has improved the clinical landscape, the emergence of the omicron variant has presented new challenges. Thus, it is timely that the European Association for the Study of the Liver provides a summary of the latest data on the impact of COVID-19 on the liver and issues guidance on the care of patients with chronic liver disease, hepatobiliary cancer, and previous liver transplantation, as the world continues to deal with the consequences of the COVID-19 pandemic.
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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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Anderson MA, Khauli MA, Goiffon RJ, Kambadakone A. Coronavirus Disease in the Abdomen. ADVANCES IN CLINICAL RADIOLOGY 2022; 4:25-35. [PMID: 37521427 PMCID: PMC9473699 DOI: 10.1016/j.yacr.2022.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Numerous abdominal manifestations have been reported in patients with coronavirus disease 2019 (COVID-19), including involvement of the luminal gastrointestinal (GI) tract, hepatobiliary system, pancreas, kidneys, spleen, and blood vessels. Although most of the associated radiological abnormalities are nonspecific without distinguishing imaging features to suggest COVID-19, unique presentations such as findings of bowel ischemia preceding gross findings of bowel necrosis have been reported. Awareness of the spectrum of abdominal manifestations of COVID-19 allows radiologists to optimize their search pattern and to raise the possibility of this etiology when appropriate. Awareness of the possible abdominal manifestations of COVID-19 should enhance detection by radiologists and improve patient care. This review provides a comprehensive overview with illustrative imaging examples of COVID-19 in the abdomen.
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Affiliation(s)
- Mark A Anderson
- Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, White Building, Room 270, Boston, MA 02114, USA
| | - Mark A Khauli
- Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, White Building, Room 270, Boston, MA 02114, USA
| | - Reece J Goiffon
- Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, White Building, Room 270, Boston, MA 02114, USA
| | - Avinash Kambadakone
- Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, White Building, Room 270, Boston, MA 02114, USA
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Mayorquín-Aguilar JM, Lara-Reyes A, Revuelta-Rodríguez LA, Flores-García NC, Ruiz-Margáin A, Jiménez-Ferreira MA, Macías-Rodríguez RU. Secondary sclerosing cholangitis after critical COVID-19: Three case reports. World J Hepatol 2022; 14:1678-1686. [PMID: 36157873 PMCID: PMC9453459 DOI: 10.4254/wjh.v14.i8.1678] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 04/04/2022] [Accepted: 08/15/2022] [Indexed: 02/06/2023] Open
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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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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Ghafoor S, Germann M, Jüngst C, Müllhaupt B, Reiner CS, Stocker D. Imaging features of COVID-19-associated secondary sclerosing cholangitis on magnetic resonance cholangiopancreatography: a retrospective analysis. Insights Imaging 2022; 13:128. [PMID: 35939241 PMCID: PMC9358102 DOI: 10.1186/s13244-022-01266-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 07/05/2022] [Indexed: 11/24/2022] Open
Abstract
Background Despite emerging reports of secondary sclerosing cholangitis (SSC) in critically ill COVID-19 patients little is known about its imaging findings. It presents as delayed progressive cholestatic liver injury with risk of progression to cirrhosis. Diagnosis cannot be made based on clinical presentation and laboratory markers alone. Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) can aid in the diagnosis. The aim of this study was to describe MRI/MRCP imaging features of COVID-19-associated SSC. Results Seventeen patients (mean age 60.5 years, 15 male) who underwent MRI/MRCP were included. All had been admitted to intensive care unit (ICU) (median duration of ICU stay 10 weeks, range, 2–28 weeks) and developed acute respiratory distress syndrome requiring mechanical ventilation. On imaging, all patients had intrahepatic bile duct strictures and 10 (58.8%) had associated upstream dilatation. Intrahepatic bile duct beading was seen in 14 cases (82.3%). Only one patient (5.9%) had extrahepatic bile duct stricturing. Patchy arterial phase hyperenhancement and high signal on T2- and diffusion-weighted images were seen in 7 cases (53.8%) and 9 cases (52.9%), respectively. Biliary casts were seen in 2 cases (11.8%). Periportal lymphadenopathy and vascular complications were not seen. Conclusion On MRI/MRCP, COVID-19-associated SSC presents with multiple intrahepatic bile duct strictures with or without upstream dilatation and intrahepatic bile duct beading. Surrounding hepatic parenchymal changes including alterations in enhancement and T2 signal are common. The extrahepatic biliary tree was typically spared and periportal lymphadenopathy was missing in all patients. Supplementary Information The online version contains supplementary material available at 10.1186/s13244-022-01266-9.
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Affiliation(s)
- Soleen Ghafoor
- Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.,University of Zurich, Zurich, Switzerland
| | - Manon Germann
- Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.,University of Zurich, Zurich, Switzerland
| | - Christoph Jüngst
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | - Beat Müllhaupt
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | - Cäcilia S Reiner
- Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.,University of Zurich, Zurich, Switzerland
| | - Daniel Stocker
- Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland. .,University of Zurich, Zurich, Switzerland.
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49
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Hunyady P, Streller L, Rüther DF, Groba SR, Bettinger D, Fitting D, Hamesch K, Marquardt JU, Mücke VT, Finkelmeier F, Sekandarzad A, Wengenmayer T, Bounidane A, Weiss F, Peiffer KH, Schlevogt B, Zeuzem S, Waidmann O, Hollenbach M, Kirstein MM, Kluwe J, Kütting F, Mücke MM. Secondary Sclerosing Cholangitis Following Coronavirus Disease 2019 (COVID-19): A Multicenter Retrospective Study. Clin Infect Dis 2022; 76:e179-e187. [PMID: 35809032 PMCID: PMC9278244 DOI: 10.1093/cid/ciac565] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 06/27/2022] [Accepted: 07/06/2022] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Secondary sclerosing cholangitis (SSC) is a rare disease with poor prognosis. Cases of SSC have been reported following coronavirus disease 2019 (COVID-SSC). The aim of this study was to compare COVID-SSC to SSC in critically ill patients (SSC-CIP) and to assess factors influencing transplant-free survival. METHODS In this retrospective, multicenter study involving 127 patients with SSC from 9 tertiary care centers in Germany, COVID-SSC was compared to SSC-CIP and logistic regression analyses were performed investigating factors impacting transplant-free survival. RESULTS Twenty-four patients had COVID-SSC, 77 patients SSC-CIP, and 26 patients other forms of SSC. COVID-SSC developed after a median of 91 days following COVID-19 diagnosis. All patients had received extensive intensive care treatment (median days of mechanical ventilation, 48). Patients with COVID-SSC and SSC-CIP were comparable in most of the clinical parameters and transplant-free survival was not different from other forms of SSC (P = .443, log-rank test). In the overall cohort, the use of ursodeoxycholic acid (UDCA) (odds ratio [OR], 0.36 [95% confidence interval {CI}, .16-.80], P = .013; log-rank P < .001) and high serum albumin levels (OR, 0.40 [95% CI, .17-.96], P = .040) were independently associated with an increased transplant-free survival, while the presence of liver cirrhosis (OR, 2.52 [95% CI, 1.01-6.25], P = .047) was associated with worse outcome. Multidrug-resistant organism (MDRO) colonization or infection did not impact patients' survival. CONCLUSIONS COVID-SSC and CIP-SSC share the same clinical phenotype, course of the disease, and risk factors for its development. UDCA may be a promising therapeutic option in SSC, though future prospective trials are needed to confirm our findings.
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Affiliation(s)
- Peter Hunyady
- Alternate Corresponding author, current address Peter Hunyady, Department of Internal Medicine I, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. Tel: +49 6301 5122,
| | - Lea Streller
- Clinic for Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Darius F Rüther
- Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | | | - Dominik Bettinger
- Department of Medicine II, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Daniel Fitting
- Department of Internal Medicine II, University Hospital Wuerzburg, Wuerzburg, Germany
| | - Karim Hamesch
- Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
| | - Jens U Marquardt
- Department of Medicine, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - Victoria T Mücke
- Department of Internal Medicine 1, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
| | - Fabian Finkelmeier
- Department of Internal Medicine 1, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
| | - Asieb Sekandarzad
- Department of Medicine III, Interdisciplinary Medical Intensive Care, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Tobias Wengenmayer
- Department of Medicine III, Interdisciplinary Medical Intensive Care, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Ayoub Bounidane
- Department of Internal Medicine 1, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
| | - Felicitas Weiss
- Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
| | - Kai Henrik Peiffer
- Department of Internal Medicine 1, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
| | | | - Stefan Zeuzem
- Department of Internal Medicine 1, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
| | - Oliver Waidmann
- Department of Internal Medicine 1, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
| | - Marcus Hollenbach
- Corresponding author, current address: Dr. med. Marcus Maximilian Mücke, Department of Internal Medicine I, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. Tel: +49 6301 5122,
| | - Martha M Kirstein
- Department of Medicine, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - Johannes Kluwe
- Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Fabian Kütting
- Clinic for Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Marcus M Mücke
- Department of Internal Medicine 1, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
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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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