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Fernández CF, Torrón BO, de Quirós Fernández MB, Garrido RSJ, Arroba CMA, Alonso IJ, Quinto AAM, Maestro ÓC, Molero FC, Nutu OA, Calvo Pulido J, Manrique Municio A, García-Sesma Pérez-Fuentes Á, Loinaz Segurola C. The Impact and Evolution of COVID-19 on Liver Transplant Recipients Throughout the Pandemic "Waves" in a Single Center. Viruses 2025; 17:273. [PMID: 40007028 PMCID: PMC11861689 DOI: 10.3390/v17020273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 02/12/2025] [Accepted: 02/13/2025] [Indexed: 02/27/2025] Open
Abstract
Liver transplant recipients (LTRs) have been considered a population group that is vulnerable to COVID-19 as they are chronically immunosuppressed patients with frequent comorbidities. This study describes the course of the SARS-CoV-2 disease from February 2020 to December 2023 along seven pandemic "waves". We carried out an observational study on 307 COVID-19 cases in a cohort of LTRs with the aim of evaluating the changes in the disease characteristics over time and determining the risk factors for severe COVID-19. An older age and serum creatinine level ≥ 2 mg/dL were found to be risk factors for hospital admission and respiratory failure. The use of calcineurin inhibitors was a protective factor for death, hospitalization, and respiratory failure from COVID-19. One hundred percent of patients who died (N = 12) were on mycophenolate mofetil, which was a determinant for respiratory failure. Azathioprine was associated with admission to the intensive care unit (ICU) and with invasive mechanical ventilation (IMV). Vaccination was a protective factor for hospitalization, respiratory failure, and mortality. The severe COVID-19 rate was higher during the first five waves, with a peak of 57.14%, and the highest mortality rate (21.43%) occurred in the fourth wave. The IMV and ICU admission rates did not show significant differences across the periods studied.
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Affiliation(s)
- Clara Fernández Fernández
- HBP and Transplant Surgery Unit, Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario “12 de Octubre”, 28041 Madrid, Spain; (B.O.T.); (M.B.d.Q.F.); (I.J.A.); (A.A.M.Q.); (Ó.C.M.); (F.C.M.); (O.A.N.); (J.C.P.); (A.M.M.); (Á.G.-S.P.-F.)
| | - Blanca Otero Torrón
- HBP and Transplant Surgery Unit, Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario “12 de Octubre”, 28041 Madrid, Spain; (B.O.T.); (M.B.d.Q.F.); (I.J.A.); (A.A.M.Q.); (Ó.C.M.); (F.C.M.); (O.A.N.); (J.C.P.); (A.M.M.); (Á.G.-S.P.-F.)
| | - Mercedes Bernaldo de Quirós Fernández
- HBP and Transplant Surgery Unit, Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario “12 de Octubre”, 28041 Madrid, Spain; (B.O.T.); (M.B.d.Q.F.); (I.J.A.); (A.A.M.Q.); (Ó.C.M.); (F.C.M.); (O.A.N.); (J.C.P.); (A.M.M.); (Á.G.-S.P.-F.)
| | | | | | - Iago Justo Alonso
- HBP and Transplant Surgery Unit, Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario “12 de Octubre”, 28041 Madrid, Spain; (B.O.T.); (M.B.d.Q.F.); (I.J.A.); (A.A.M.Q.); (Ó.C.M.); (F.C.M.); (O.A.N.); (J.C.P.); (A.M.M.); (Á.G.-S.P.-F.)
- School of Medicine, Complutense University of Madrid, Avenida de Cordoba s/n, 28041 Madrid, Spain
| | - Alberto Alejandro Marcacuzco Quinto
- HBP and Transplant Surgery Unit, Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario “12 de Octubre”, 28041 Madrid, Spain; (B.O.T.); (M.B.d.Q.F.); (I.J.A.); (A.A.M.Q.); (Ó.C.M.); (F.C.M.); (O.A.N.); (J.C.P.); (A.M.M.); (Á.G.-S.P.-F.)
- School of Medicine, Complutense University of Madrid, Avenida de Cordoba s/n, 28041 Madrid, Spain
| | - Óscar Caso Maestro
- HBP and Transplant Surgery Unit, Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario “12 de Octubre”, 28041 Madrid, Spain; (B.O.T.); (M.B.d.Q.F.); (I.J.A.); (A.A.M.Q.); (Ó.C.M.); (F.C.M.); (O.A.N.); (J.C.P.); (A.M.M.); (Á.G.-S.P.-F.)
- School of Medicine, Complutense University of Madrid, Avenida de Cordoba s/n, 28041 Madrid, Spain
| | - Félix Cambra Molero
- HBP and Transplant Surgery Unit, Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario “12 de Octubre”, 28041 Madrid, Spain; (B.O.T.); (M.B.d.Q.F.); (I.J.A.); (A.A.M.Q.); (Ó.C.M.); (F.C.M.); (O.A.N.); (J.C.P.); (A.M.M.); (Á.G.-S.P.-F.)
- School of Medicine, Complutense University of Madrid, Avenida de Cordoba s/n, 28041 Madrid, Spain
| | - Oana Anisa Nutu
- HBP and Transplant Surgery Unit, Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario “12 de Octubre”, 28041 Madrid, Spain; (B.O.T.); (M.B.d.Q.F.); (I.J.A.); (A.A.M.Q.); (Ó.C.M.); (F.C.M.); (O.A.N.); (J.C.P.); (A.M.M.); (Á.G.-S.P.-F.)
- School of Medicine, Complutense University of Madrid, Avenida de Cordoba s/n, 28041 Madrid, Spain
| | - Jorge Calvo Pulido
- HBP and Transplant Surgery Unit, Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario “12 de Octubre”, 28041 Madrid, Spain; (B.O.T.); (M.B.d.Q.F.); (I.J.A.); (A.A.M.Q.); (Ó.C.M.); (F.C.M.); (O.A.N.); (J.C.P.); (A.M.M.); (Á.G.-S.P.-F.)
- School of Medicine, Complutense University of Madrid, Avenida de Cordoba s/n, 28041 Madrid, Spain
| | - Alejandro Manrique Municio
- HBP and Transplant Surgery Unit, Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario “12 de Octubre”, 28041 Madrid, Spain; (B.O.T.); (M.B.d.Q.F.); (I.J.A.); (A.A.M.Q.); (Ó.C.M.); (F.C.M.); (O.A.N.); (J.C.P.); (A.M.M.); (Á.G.-S.P.-F.)
- School of Medicine, Complutense University of Madrid, Avenida de Cordoba s/n, 28041 Madrid, Spain
| | - Álvaro García-Sesma Pérez-Fuentes
- HBP and Transplant Surgery Unit, Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario “12 de Octubre”, 28041 Madrid, Spain; (B.O.T.); (M.B.d.Q.F.); (I.J.A.); (A.A.M.Q.); (Ó.C.M.); (F.C.M.); (O.A.N.); (J.C.P.); (A.M.M.); (Á.G.-S.P.-F.)
- School of Medicine, Complutense University of Madrid, Avenida de Cordoba s/n, 28041 Madrid, Spain
| | - Carmelo Loinaz Segurola
- HBP and Transplant Surgery Unit, Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario “12 de Octubre”, 28041 Madrid, Spain; (B.O.T.); (M.B.d.Q.F.); (I.J.A.); (A.A.M.Q.); (Ó.C.M.); (F.C.M.); (O.A.N.); (J.C.P.); (A.M.M.); (Á.G.-S.P.-F.)
- Instituto de Investigación, Hospital “12 de Octubre” (imas12), 28041 Madrid, Spain
- School of Medicine, Complutense University of Madrid, Avenida de Cordoba s/n, 28041 Madrid, Spain
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Hashem M, El-Kassas M. Diagnosis, treatment protocols, and outcomes of liver transplant recipients infected with COVID-19. World J Clin Cases 2023; 11:2140-2159. [PMID: 37122505 PMCID: PMC10131019 DOI: 10.12998/wjcc.v11.i10.2140] [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: 09/02/2022] [Revised: 01/20/2023] [Accepted: 03/09/2023] [Indexed: 03/30/2023] Open
Abstract
Several cases of fatal pneumonia during November 2019 were linked initially to severe acute respiratory syndrome coronavirus 2, which the World Health Organization later designated as coronavirus disease 2019 (COVID-19). The World Health Organization declared COVID-19 as a pandemic on March 11, 2020. In the general population, COVID-19 severity can range from asymptomatic/mild symptoms to seriously ill. Its mortality rate could be as high as 49%. The Centers for Disease Control and Prevention have acknowledged that people with specific underlying medical conditions, among those who need immunosuppression after solid organ transplantation (SOT), are at an increased risk of developing severe illness from COVID-19. Liver transplantation is the second most prevalent SOT globally. Due to their immunosuppressed state, liver transplant (LT) recipients are more susceptible to serious infections. Therefore, comorbidities and prolonged immunosuppression among SOT recipients enhance the likelihood of severe COVID-19. It is crucial to comprehend the clinical picture, immunosuppressive management, prognosis, and prophylaxis of COVID-19 infection because it may pose a danger to transplant recipients. This review described the clinical and laboratory findings of COVID-19 in LT recipients and the risk factors for severe disease in this population group. In the following sections, we discussed current COVID-19 therapy choices, reviewed standard practice in modifying immunosuppressant regimens, and outlined the safety and efficacy of currently licensed drugs for inpatient and outpatient management. Additionally, we explored the clinical outcomes of COVID-19 in LT recipients and mentioned the efficacy and safety of vaccination use.
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Affiliation(s)
- Mai Hashem
- Fellow of Tropical Medicine and Gastroenterology, Assiut University Hospital, Assiut 71515, Egypt
| | - Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo 11795, Egypt
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He YF, Jiang ZG, Wu N, Bian N, Ren JL. Correlation between COVID-19 and hepatitis B: A systematic review. World J Gastroenterol 2022; 28:6599-6618. [PMID: 36569273 PMCID: PMC9782843 DOI: 10.3748/wjg.v28.i46.6599] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Revised: 10/29/2022] [Accepted: 11/19/2022] [Indexed: 12/08/2022] Open
Abstract
BACKGROUND There is growing evidence that patients with coronavirus disease 2019 (COVID-19) frequently present with liver impairment. Hepatitis B virus (HBV) remains a major public health threat in current society. Both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and HBV can cause liver damage, and current findings on whether HBV infection increases disease severity in COVID-19 patients are inconsistent, and whether SARS-CoV-2 infection accelerates hepatitis B progression or leads to a worse prognosis in hepatitis B patients has not been adequately elucidated. AIM To explore the complex relationship between COVID-19 and hepatitis B in order to inform the research and management of patients co-infected with SARS-CoV-2 and HBV. METHODS An experienced information specialist searched the literature in the following online databases: PubMed, China National Knowledge Infrastructure, Google Scholar, Scopus, Wiley, Web of Science, Cochrane, and ScienceDirect. The literature published from December 2019 to September 1, 2022 was included in the search. We also searched medRxiv and bioRxiv for gray literature and manually scanned references of included articles. Articles reporting studies conducted in humans discussing hepatitis B and COVID-19 were included. We excluded duplicate publications. News reports, reports, and other gray literature were included if they contained quantifiable evidence (case reports, findings, and qualitative analysis). Some topics that included HBV or COVID-19 samples but did not have quantitative evidence were excluded from the review. RESULTS A total of 57 studies were eligible and included in this review. They were from 11 countries, of which 33 (57.9%) were from China. Forty-two of the 57 studies reported abnormalities in liver enzymes, three mainly reported abnormalities in blood parameters, four indicated no significant liver function alterations, and another eight studies did not provide data on changes in liver function. Fifty-seven studies were retrospective and the total number of co-infections was 1932, the largest sample size was 7723, and the largest number of co-infections was 353. Most of the studies suggested an interaction between hepatitis B and COVID-19, while 12 studies clearly indicated no interaction between hepatitis B and COVID-19. Six of the 57 studies clearly reported HBV activation. Six studies were related to liver transplant patients. CONCLUSION There is some association between COVID-19 and hepatitis B. Future high-quality randomized trials are needed to further elucidate the interaction between COVID-19 and hepatitis B.
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Affiliation(s)
- Yan-Fei He
- Health Management Center, The Sixth Medical Center, Chinese PLA General Hospital, Beijing 100048, China
| | - Zhi-Gang Jiang
- Department of Statistics, Zunyi Medical University, Guizhou 563006, Guizhou Province, China
| | - Ni Wu
- Health Management Center, The Sixth Medical Center, Chinese PLA General Hospital, Beijing 100048, China
| | - Ning Bian
- Health Management Center, The Sixth Medical Center, Chinese PLA General Hospital, Beijing 100048, China
| | - Jun-Lin Ren
- Department of Infection Control, The Sixth Medical Center, Chinese PLA General Hospital, Beijing 100048, China
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Punga D, Isac S, Paraipan C, Cotorogea M, Stefan A, Cobilinschi C, Vacaroiu IA, Tulin R, Ionescu D, Droc G. Impact of COVID-19 Infection on Liver Transplant Recipients: Does It Make Any Difference? Cureus 2022; 14:e22687. [PMID: 35386162 PMCID: PMC8967117 DOI: 10.7759/cureus.22687] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/27/2022] [Indexed: 11/25/2022] Open
Abstract
The first case of coronavirus disease 2019 (COVID-19) was diagnosed in December 2019 in Wuhan, China. Since then, this novel infectious disease, caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has grown into a pandemic with over 330 million infected individuals worldwide, many of them with innate or acquired immunosuppression. Liver transplantation (LT) is offered as a curative therapy for end-stage liver disease as well as for acute liver failure cases. Advances in immunosuppressive therapy decreased the rates of acute and chronic graft rejection, significantly improving the quality of life. Liver transplant recipients are considered at particularly high risk for developing critical COVID-19 infection because of their chronic immunosuppressed state. Available data are heterogeneous, and the mortality rate is variably reported in the literature. There is controversy regarding whether their immunosuppressive status is a risk or a protective factor for developing severe respiratory disease. Moreover, the mechanism of action is still unclear. We report the clinical outcome of three liver transplant recipients who had COVID-19 pneumonia at different moments following liver transplantation. All patients received a standard immunosuppression regimen and specific antiviral therapy, requiring no invasive mechanical ventilation. They were discharged from the hospital with no long-term COVID-19 complications.
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An W, Wang Q, Kim TE, Kang JS. Clinical characteristics and outcome of coronavirus disease 2019 infection in patients with solid organ transplants: A systematic review and meta-analysis. J Infect Public Health 2022; 15:365-372. [PMID: 35193818 PMCID: PMC8857642 DOI: 10.1016/j.jiph.2022.02.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 01/03/2022] [Accepted: 02/06/2022] [Indexed: 12/24/2022] Open
Affiliation(s)
- Wen An
- Department of Pharmacology & Clinical Pharmacology, College of Medicine, Hanyang University, Seoul, South Korea.
| | - Qiuyang Wang
- Department of Central China Research Institute of Health, Xinxiang Medical University, Xinxiang, China.
| | - Tae-Eun Kim
- Department of Clinical Pharmacology, Konkuk University Hospital, Seoul, South Korea.
| | - Ju-Seop Kang
- Department of Pharmacology & Clinical Pharmacology, College of Medicine, Hanyang University, Seoul, South Korea.
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Stainer A, Amati F, Suigo G, Simonetta E, Gramegna A, Voza A, Aliberti S. COVID-19 in Immunocompromised Patients: A Systematic Review. Semin Respir Crit Care Med 2021; 42:839-858. [PMID: 34918325 DOI: 10.1055/s-0041-1740110] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was first identified as a novel coronavirus in Wuhan, Hubei province, central China, in December 2019, and is responsible for the 2019-to-present pandemic. According to the most recent data released by the World Health Organization, more than 200 million people have been infected by SARS-CoV-2 so far, and more than 4 million people died worldwide. Although our knowledge on SARS-CoV-2 and COVID-19 is constantly growing, data on COVID-19 in immunocompromised patients are still limited. The aim of the present systematic review is to describe clinical picture, disease severity, proposed treatment regimen, and response to vaccination in patients with different types and severity of immunosuppression.
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Affiliation(s)
- Anna Stainer
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.,Respiratory Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Francesco Amati
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.,Respiratory Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Giulia Suigo
- Respiratory Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Edoardo Simonetta
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.,Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Respiratory Department, Milan, Italy
| | - Andrea Gramegna
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.,Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Respiratory Department, Milan, Italy
| | - Antonio Voza
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.,Emergency Medicine Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Stefano Aliberti
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.,Respiratory Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
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Yadav DK, Adhikari VP, Ling Q, Liang T. Immunosuppressants in Liver Transplant Recipients With Coronavirus Disease 2019: Capability or Catastrophe?-A Systematic Review and Meta-Analysis. Front Med (Lausanne) 2021; 8:756922. [PMID: 34859012 PMCID: PMC8632009 DOI: 10.3389/fmed.2021.756922] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 10/06/2021] [Indexed: 12/15/2022] Open
Abstract
Background: The probable impact of a maintenance immunosuppressant (IS) on liver transplant (LT) recipients with coronavirus disease 2019 (COVID-19) remains unexplored. Our specific aim was to approximate the prognosis of LT recipients with COVID-19 on the standard maintenance IS. Method: We searched separate databases for the qualified studies in between December 2019 and June 25, 2021. Ultimately, a meta-analysis was carried out using a fixed-effect or random-effect model based on the heterogeneity. Results: In a total of eight studies and 509 LT recipients with COVID-19, the pooled rates of severity and mortality during all the combined immunosuppressive therapies were 22.4 and 19.5%, respectively. Our study sufficiently showed that an immunosuppressive therapy in LT recipients with COVID-19 was significantly associated with a non-severe COVID-19 [odds ratio (OR): 11.49, 95% CI: 4.17-31.65; p < 0.001] and the survival of the patients (OR: 17.64, 95% CI: 12.85-24.22; p < 0.001). Moreover, mammalian target of rapamycin inhibitor (mTORi) typically had the lowest rate of severity and mortality compared to other ISs such as calcineurin inhibitors (CNIs), steroids, and antimetabolites, i.e., severity (13.5 vs. 21.1, 24.7, and 26.3%) and mortality (8.3 vs. 15, 17.2, and 12.1%), respectively. Contrary to the general opinions, our meta-analysis showed comorbidities such as diabetes, hypertension, cardiopulmonary disorders, chronic kidney disease (CKD), age >60, the duration of LT to the diagnosis of COVID-19, primary disease for LT, and obesity were not significantly associated with the severity and mortality in LT recipients with COVID-19 under an immunosuppressive therapy. However, our pooled analysis found that LT recipients with COVID-19 and without comorbidities have a less severe disease and low mortality rate compared to those with both COVID-19 and comorbidities. Conclusions: In conclusion, LT recipients with COVID-19 undergoing immunosuppressive therapies are not significantly associated with the severity and mortality. Therefore, taking the risk of organ rejection into a key consideration, a complete withdrawal of the IS may not be wise. However, mycophenolate mofetil (MMF) might be discontinued or replaced from an immunosuppressive regimen with the CNIs- or mTORis-based immunosuppressive therapy in some selected LT recipients with COVID-19, depending upon the severity of the disease.
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Affiliation(s)
- Dipesh Kumar Yadav
- Department of Hepatobiliary Surgery & Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
- Zhejiang Provincial Innovation Center for the Study of Pancreatic Diseases, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for the Study of Hepatobiliary & Pancreatic Diseases, Hangzhou, China
- Cancer Center, Zhejiang University, Hangzhou, China
| | - Vishnu Prasad Adhikari
- Department of Hepatobiliary Surgery & Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for the Study of Hepatobiliary & Pancreatic Diseases, Hangzhou, China
| | - Qi Ling
- Department of Hepatobiliary Surgery & Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for the Study of Hepatobiliary & Pancreatic Diseases, Hangzhou, China
| | - Tingbo Liang
- Department of Hepatobiliary Surgery & Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
- Zhejiang Provincial Innovation Center for the Study of Pancreatic Diseases, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for the Study of Hepatobiliary & Pancreatic Diseases, Hangzhou, China
- Cancer Center, Zhejiang University, Hangzhou, China
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Loinaz-Segurola C, Marcacuzco-Quinto A, Fernández-Ruiz M. Coronavirus disease 2019 in liver transplant patients: Clinical and therapeutic aspects. World J Hepatol 2021; 13:1299-1315. [PMID: 34786167 PMCID: PMC8568575 DOI: 10.4254/wjh.v13.i10.1299] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 06/17/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has profoundly impacted liver transplant (LT) activity across the world, with notable decreases in the number of donations and procedures in most Western countries, in particular throughout the first wave. The cumulative incidence of COVID-19 in LT recipients (with estimates ranging from 0.34% to 1.56%) appears to be at least comparable to that observed for the general population. Clinical and radiological features at presentation are also similar to non-transplant patients. The risk of death among LT recipients requiring hospital admission is high (from 12% to 19%), although some authors have suggested that overall mortality may be actually lower compared to the general non-transplant population. It is likely that these poor outcomes may be mainly influenced by the older age and higher comorbidity burden of LT recipients, rather than by the transplant status itself. In fact, it has been hypothesized that post-transplant immunosuppression would exert a protective role, with special focus on tacrolimus-containing regimens. There is scarce evidence to guide the optimal management of post-transplant COVID-19 and the use of antiviral or immunomodulatory therapies, although both clinical practice and guidelines support the dose reduction or withdrawal of anti-proliferative agents such as mofetil mycophenolate. Preliminary reports suggest that the antibody response to messenger RNA vaccines is significantly impaired as compared to non-immunocompromised individuals, in line with other transplant populations. Finally, it is foreseeable that the future will be conditioned by the emerging variants of severe acute respiratory syndrome coronavirus 2 with increased transmissibility among LT recipients.
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Affiliation(s)
- Carmelo Loinaz-Segurola
- HBP and Transplant Surgery Unit. Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Universidad Complutense, Madrid 28041, Spain.
| | - Alberto Marcacuzco-Quinto
- HBP and Transplant Surgery Unit. Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Universidad Complutense, Madrid 28041, Spain
| | - Mario Fernández-Ruiz
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Universidad Complutense, Madrid 28041, Spain
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9
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Quante M, Brake L, Tolios A, Della Penna A, Steidle C, Gruendl M, Grishina A, Haeberle H, Guthoff M, Tullius SG, Königsrainer A, Nadalin S, Löffler MW. SARS-CoV-2 in Solid Organ Transplant Recipients: A Structured Review of 2020. Transplant Proc 2021; 53:2421-2434. [PMID: 34551880 PMCID: PMC8364801 DOI: 10.1016/j.transproceed.2021.08.019] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 08/04/2021] [Accepted: 08/10/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is challenging health systems all over the world. Particularly high-risk groups show considerable mortality rates after infection. In 2020, a huge number of case reports, case series, and consecutively various systematic reviews have been published reporting on morbidity and mortality risk connected with SARS-CoV-2 in solid organ transplant (SOT) recipients. However, this vast array of publications resulted in an increasing complexity of the field, overwhelming even for the expert reader. METHODS We performed a structured literature review comprising electronic databases, transplant journals, and literature from previous systematic reviews covering the entire year 2020. From 164 included articles, we identified 3451 cases of SARS-CoV-2-infected SOT recipients. RESULTS Infections resulted in a hospitalization rate of 84% and 24% intensive care unit admissions in the included patients. Whereas 53.6% of patients were reported to have recovered, cross-sectional overall mortality reported after coronavirus disease 2019 (COVID-19) was at 21.1%. Synoptic data concerning immunosuppressive medication attested to the reduction or withdrawal of antimetabolites (81.9%) and calcineurin inhibitors (48.9%) as a frequent adjustment. In contrast, steroids were reported to be increased in 46.8% of SOT recipients. CONCLUSIONS COVID-19 in SOT recipients is associated with high morbidity and mortality worldwide. Conforming with current guidelines, modifications of immunosuppressive therapies mostly comprised a reduction or withdrawal of antimetabolites and calcineurin inhibitors, while frequently maintaining or even increasing steroids. Here, we provide an accessible overview to the topic and synoptic estimates of expectable outcomes regarding in-hospital mortality of SOT recipients with COVID-19.
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Affiliation(s)
- Markus Quante
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Linda Brake
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Alexander Tolios
- Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria; Center for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria; Center for Medical Statistics, Informatics, and Intelligent Systems, Institute of Artificial Intelligence, Medical University of Vienna, Vienna, Austria
| | - Andrea Della Penna
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Christoph Steidle
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Magdalena Gruendl
- Department of Epidemiology, Technical University Munich, Munich, Germany
| | - Anna Grishina
- Department of Pediatrics I, University Medicine Essen, Essen, Germany
| | - Helene Haeberle
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Tübingen, Germany
| | - Martina Guthoff
- Department of Diabetology, Endocrinology, Nephrology, Section of Nephrology and Hypertension, University Hospital Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich, University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
| | - Stefan G Tullius
- Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Alfred Königsrainer
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany; Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies," University of Tübingen, Tübingen, Germany
| | - Silvio Nadalin
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Markus W Löffler
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany; Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies," University of Tübingen, Tübingen, Germany; Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, Tübingen, Germany; Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany.
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10
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Kullar R, Patel AP, Saab S. COVID-19 in Liver Transplant Recipients. J Clin Transl Hepatol 2021; 9:545-550. [PMID: 34447684 PMCID: PMC8369016 DOI: 10.14218/jcth.2020.00098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 12/11/2020] [Accepted: 02/04/2021] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND AND AIMS Coronavirus disease 2019 (COVID-19) has infected over 93 million people worldwide as of January 14, 2021. Various studies have gathered data on liver transplant patients infected with COVID-19. Here, we discuss the presentation of COVID-19 in immunosuppressed patients with prior liver transplants. We also evaluate patient outcomes after infection. METHODS We searched the PubMed database for all studies focused on liver transplant patients with COVID-19. RESULTS We identified eight studies that evaluated COVID-19 infection in liver transplant patients (n=494). Hypertension was the most prevalent comorbidity in our cohort. Calcineurin inhibitors were the most common immunosuppressant medications in the entire cohort. The average time from liver transplant to COVID-19 infection in our cohort was 74.1 months. Fever and cough, at 70% and 62% respectively, were the most common symptoms in our review. In total, 50% of the patients received hydroxychloroquine as treatment for COVID-19. The next most prevalent treatment was azithromycin, given to 30% of patients in our cohort. In total, 80% of the patients were admitted to a hospital and 17% required intensive care unit-level care, with 21% having required mechanical ventilation. Overall mortality was 17% in our review. CONCLUSIONS Given the immunocompromised status of liver transplant patients, more intensive surveillance is necessary for severe cases of COVID-19 infection. As liver transplantations have been restricted during the COVID-19 pandemic, further investigation is warranted for studying the risk of COVID-19 infection in liver transplant patients.
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Affiliation(s)
| | - Ankur Prakash Patel
- David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, CA, USA
| | - Sammy Saab
- David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, CA, USA
- Correspondence to: Sammy Saab, Pfleger Liver Institute, UCLA Medical Center, 200 Medical Plaza, Suite 214, Los Angeles, CA 90095, USA. Tel: +1-310-206-6705, Fax: +1-310-206-4197, E-mail:
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11
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Fernández-Ruiz M, Olea B, Almendro-Vázquez P, Giménez E, Marcacuzco A, San Juan R, Justo I, Calvo-Pulido J, García-Sesma Á, Manrique A, Caso O, Cambra F, Talayero P, López-Medrano F, Remigia MJ, Ruiz-Merlo T, Parra P, Paz-Artal E, Jiménez C, Loinaz C, Navarro D, Laguna-Goya R, Aguado JM. T cell-mediated response to SARS-CoV-2 in liver transplant recipients with prior COVID-19. Am J Transplant 2021; 21:2785-2794. [PMID: 34092033 PMCID: PMC8222887 DOI: 10.1111/ajt.16708] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 05/11/2021] [Accepted: 05/30/2021] [Indexed: 01/25/2023]
Abstract
Whether immunosuppression impairs severe acute respiratory syndrome coronavirus 2-specific T cell-mediated immunity (SARS-CoV-2-CMI) after liver transplantation (LT) remains unknown. We included 31 LT recipients in whom SARS-CoV-2-CMI was assessed by intracellular cytokine staining (ICS) and interferon (IFN)-γ FluoroSpot assay after a median of 103 days from COVID-19 diagnosis. Serum SARS-CoV-2 IgG antibodies were measured by ELISA. A control group of nontransplant immunocompetent patients were matched (1:1 ratio) by age and time from diagnosis. Post-transplant SARS-CoV-2-CMI was detected by ICS in 90.3% (28/31) of recipients, with higher proportions for IFN-γ-producing CD4+ than CD8+ responses (93.5% versus 83.9%). Positive spike-specific and nucleoprotein-specific responses were found by FluoroSpot in 86.7% (26/30) of recipients each, whereas membrane protein-specific response was present in 83.3% (25/30). An inverse correlation was observed between the number of spike-specific IFN-γ-producing SFUs and time from diagnosis (Spearman's rho: -0.418; p value = .024). Two recipients (6.5%) failed to mount either T cell-mediated or IgG responses. There were no significant differences between LT recipients and nontransplant patients in the magnitude of responses by FluoroSpot to any of the antigens. Most LT recipients mount detectable-but declining over time-SARS-CoV-2-CMI after a median of 3 months from COVID-19, with no meaningful differences with immunocompetent patients.
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Affiliation(s)
- Mario Fernández-Ruiz
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
| | - Beatriz Olea
- Department of Microbiology, Hospital Clínico Universitario, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain
| | - Patricia Almendro-Vázquez
- Department of Immunology, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
| | - Estela Giménez
- Department of Microbiology, Hospital Clínico Universitario, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain
| | - Alberto Marcacuzco
- Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
| | - Rafael San Juan
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
- Department of Medicine, Universidad Complutense, Madrid, Spain
| | - Iago Justo
- Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
| | - Jorge Calvo-Pulido
- Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
| | - Álvaro García-Sesma
- Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
| | - Alejandro Manrique
- Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
| | - Oscar Caso
- Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
| | - Félix Cambra
- Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
| | - Paloma Talayero
- Department of Immunology, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
| | - Francisco López-Medrano
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
- Department of Medicine, Universidad Complutense, Madrid, Spain
| | - María José Remigia
- Department of Hematology, Hospital Clínico Universitario, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain
| | - Tamara Ruiz-Merlo
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
| | - Patricia Parra
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
| | - Estela Paz-Artal
- Department of Immunology, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
| | - Carlos Jiménez
- Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
- Department of Surgery, Universidad Complutense, Madrid, Spain
| | - Carmelo Loinaz
- Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
- Department of Surgery, Universidad Complutense, Madrid, Spain
| | - David Navarro
- Department of Microbiology, Hospital Clínico Universitario, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain
- School of Medicine, Universidad de Valencia, Valencia, Spain
| | - Rocío Laguna-Goya
- Department of Immunology, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
| | - José M. Aguado
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
- Department of Medicine, Universidad Complutense, Madrid, Spain
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12
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Kulkarni AV, Tevethia HV, Premkumar M, Arab JP, Candia R, Kumar K, Kumar P, Sharma M, Rao PN, Reddy DN. Impact of COVID-19 on liver transplant recipients-A systematic review and meta-analysis. EClinicalMedicine 2021; 38:101025. [PMID: 34278287 PMCID: PMC8276632 DOI: 10.1016/j.eclinm.2021.101025] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Revised: 06/21/2021] [Accepted: 06/28/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Immunosuppression and comorbidities increase the risk of severe coronavirus disease-2019 (COVID-19) in solid organ transplant (SOT) recipients. The outcomes of COVID-19 in liver transplant (LT) recipients remain unclear. We aimed to analyse the outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in LT recipients. METHODS The electronic databases were searched for articles published from 1 December 2019 to 20 May 2021 with MeSH terms COVID-19, SARS-CoV-2, and liver transplantation. Studies reporting outcomes in more than 10 LT recipients were included for analysis. LT vs non-LT patients with COVID-19 infection were compared for all-cause mortality, which was the primary outcome studied. We also evaluated the relation between the timing of COVID-19 infection post-LT (< one year vs > one year) and mortality. FINDINGS Eighteen articles reporting 1,522 COVID-19 infected LT recipients were included for the systematic review. The mean age (standard deviation [SD]) was 60·38 (5·24) years, and 68·5% were men. The mean time (SD) to COVID-19 infection was 5·72 (1·75) years. Based on 17 studies (I2 = 7·34) among 1,481 LT recipients, the cumulative incidence of mortality was 17·4% (95% confidence interval [CI], 15·4-19·6). Mortality was comparable between LT (n = 610) and non-LT (n = 239,704) patients, based on four studies (odds ratio [OR], 0·8 [0·6-1·08]; P = 0·14). Additionally, there was no significant difference in mortality between those infected within one year vs after one year of LT (OR, 1·5 [0·63-3·56]; P = 0·35). The cumulative incidence of graft dysfunction was 2·3% (1·3-4·1). Nearly 23% (20·71-25) of the LT patients developed severe COVID-19 infection. Before infection, 71% and 49% of patients were on tacrolimus and mycophenolate mofetil, respectively. Immunosuppression was modified in 55·9% (38·1-72·2) patients after COVID-19 infection. INTERPRETATION LT and non-LT patients with COVID-19 have a similar risk of adverse outcomes.
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Affiliation(s)
- Anand V. Kulkarni
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
| | | | | | - Juan Pablo Arab
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Roberto Candia
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Karan Kumar
- Department of Hepatology, Pacific Institute of Medical Sciences, Udaipur, India
| | - Pramod Kumar
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Mithun Sharma
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Padaki Nagaraja Rao
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
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13
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Sharma P, Kumar A, Anikhindi S, Bansal N, Singla V, Shivam K, Arora A. Effect of COVID-19 on Pre-existing Liver disease: What Hepatologist Should Know? J Clin Exp Hepatol 2021; 11:484-493. [PMID: 33398223 PMCID: PMC7774459 DOI: 10.1016/j.jceh.2020.12.006] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 12/24/2020] [Indexed: 02/07/2023] Open
Abstract
COVID-19 is characterized by predominant respiratory and gastrointestinal symptoms. Liver enzymes derangement is seen in 15-55% of the patients. Advanced age, hypertension, diabetes, obesity, malignancy, and cardiovascular disease predispose them to severe disease and the need for hospitalization. Data on pre-existing liver disease in patients with COVID-19 is limited, and most studies had only 3-8% of these patients. Patients with metabolic dysfunction-associated fatty liver (MAFLD) had shown a 4-6 fold increase in severity of COVID-19, and its severity and mortality increased in patients with higher fibrosis scores. Patients with chronic liver disease had shown that cirrhosis is an independent predictor of severity of COVID-19 with increased hospitalization and mortality. Increase in Child Turcotte Pugh (CTP) score and model for end-stage liver disease (MELD) score increases the mortality in these patients. Few case reports had shown SARS-CoV-2 as an acute event in the decompensation of underlying chronic liver disease. Immunosuppression should be reduced prophylactically in patients with autoimmune liver disease and post-transplantation with no COVID-19. Hydroxychloroquine and remdesivir is found to be safe in limited studies in a patient with cirrhosis and COVID-19. For hepatologists, cirrhosis with COVID-19 is a pertinent issue as the present pandemic will have severe disease in patients with chronic liver disease leading to more hospitalization and decompensation.
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Key Words
- AASLD, American Association for the Study of Liver Diseases
- ACE2, Angiotensin-Converting Enzyme 2
- AIH, Autoimmune Hepatitis
- ALP, Alkaline Phosphatase
- AST/ALT, Aspartate and Alanine Aminotransferase
- CHF, Congestive Heart Failure
- CKD, Chronic Kidney Disease
- CLD, Chronic Liver Disease
- CLIF-OC, Chronic Liver Failure Organ Cirrhosis
- CLIF-OF, Chronic Liver Failure Organ Failure
- COVID-19
- CRP, C Reactive Protein
- CTP, Child Turcotte Pugh
- Cirrhosis
- DILI, Drug-Induced Liver Injury
- EASL, European Association for the Study of Liver
- HBC, Hepatitis C
- HBV, Hepatitis B
- HCC, Hepatocellular Carcinoma
- HCQ, Hydoxycholoroquine
- LT, Liver Transplantation
- Liver disease
- MAFLD, Metabolic Associated Fatty Liver Disease
- MELD, Model for End-stage Liver Disease
- NAFLD, Nonalcoholic Fatty Liver Disease
- PPE, Personal Protection Kit
- RR, Relative Risk
- RTPCR, Reverse Transcription-Polymerase Chain Reaction
- Severity
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Affiliation(s)
- Praveen Sharma
- Department of Gastroenterology Sir Ganga Ram Hospital New Delhi, India
| | - Ashish Kumar
- Department of Gastroenterology Sir Ganga Ram Hospital New Delhi, India
| | | | - Naresh Bansal
- Department of Gastroenterology Sir Ganga Ram Hospital New Delhi, India
| | - Vikas Singla
- Department of Gastroenterology Sir Ganga Ram Hospital New Delhi, India
| | - Khare Shivam
- Department of Gastroenterology Sir Ganga Ram Hospital New Delhi, India
| | - Anil Arora
- Department of Gastroenterology Sir Ganga Ram Hospital New Delhi, India
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14
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Jayant K, Reccia I, Virdis F, Pyda JS, Bachul PJ, di Sabato D, Barth RN, Fung J, Baker T, Witkowski P. COVID-19 in hospitalized liver transplant recipients: An early systematic review and meta-analysis. Clin Transplant 2021; 35:e14246. [PMID: 33555058 PMCID: PMC7995098 DOI: 10.1111/ctr.14246] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 01/23/2021] [Accepted: 01/31/2021] [Indexed: 01/08/2023]
Abstract
Adverse clinical outcomes related to SARS-CoV-2 infection among liver transplant (LTx) recipients remain undefined. We performed a meta-analysis to determine the pooled prevalence of outcomes among hospitalized LTx recipients with COVID-19. A database search of literature published between December 1, 2019, and November 20, 2020, was performed per PRISMA guidelines. Twelve studies comprising 517 hospitalized LTx recipients with COVID-19 were analyzed. Common presenting symptoms were fever (71%), cough (62%), dyspnea (48%), and diarrhea (28%). Approximately 77% (95% CI, 61%-93%) of LTx recipients had a history of liver cirrhosis. The most prevalent comorbidities were hypertension (55%), diabetes (45%), and cardiac disease (21%). In-hospital mortality was 20% (95% CI, 13%-28%) and rose to 41% (95% CI, 19%-63%) (P < 0.00) with ICU admission. Additional subgroup analysis demonstrated a higher mortality risk in the elderly (>60-65 years) (OR 4.26; 95% CI, 2.14-8.49). There was no correlation in respect to sex or time since transplant. In summary, LTx recipients with COVID-19 had a high prevalence of dyspnea and gastrointestinal symptoms. In-hospital mortality was comparable to non-transplant populations with similar comorbidities but appeared to be less than what is reported elsewhere for cirrhotic patients (26%-40%). Importantly, the observed high case fatality in the elderly could be due to age-associated comorbidities.
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Affiliation(s)
- Kumar Jayant
- The Transplantation InstituteDepartment of SurgeryUniversity of ChicagoChicagoILUSA
- Department of Surgery and CancerImperial College LondonLondonUK
| | - Isabella Reccia
- Department of Surgery and CancerImperial College LondonLondonUK
| | | | - Jordan S. Pyda
- The Transplantation InstituteDepartment of SurgeryUniversity of ChicagoChicagoILUSA
- Department of SurgeryBeth Israel Deaconess Medical CenterBostonMAUSA
| | - Piotr J. Bachul
- The Transplantation InstituteDepartment of SurgeryUniversity of ChicagoChicagoILUSA
| | - Diego di Sabato
- The Transplantation InstituteDepartment of SurgeryUniversity of ChicagoChicagoILUSA
| | - Rolf N. Barth
- The Transplantation InstituteDepartment of SurgeryUniversity of ChicagoChicagoILUSA
| | - John Fung
- The Transplantation InstituteDepartment of SurgeryUniversity of ChicagoChicagoILUSA
| | - Talia Baker
- The Transplantation InstituteDepartment of SurgeryUniversity of ChicagoChicagoILUSA
| | - Piotr Witkowski
- The Transplantation InstituteDepartment of SurgeryUniversity of ChicagoChicagoILUSA
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15
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Samidoust P, Nikoupour H, Hemmati H, Samidoust A. Clinical Manifestations and Characterization of COVID-19 in Liver Transplant Recipients: A Systematic Review of Case Reports and Case Series. Ethiop J Health Sci 2021; 31:429-438. [PMID: 34158795 PMCID: PMC8188090 DOI: 10.4314/ejhs.v31i2.26] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 12/06/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND This systematic review is conducted to explore available information on clinical presentations, laboratory finding and outcomes of SARS-COV-2 in liver transplant patients. METHODS We searched four databases for relevant terms related to COVID-19 and liver transplantation and collected both case reports and case series on liver transplantation published up to the end of September 2020. RESULTS After initial screening of irrelevant articles, 25 studies were included and analyzed in this review. Among the 59 patients included, 78.3% were over 50 years old, and 71.6% were males. The majority of patients (93.3%) were hospitalized. The most common presenting symptoms were fever (72.9%) followed by dyspnea and cough (54.2%). The majority of patients revealed a high level of CRP (64.3%). Moreover, high level ALT, AST and ALP were reported in 64.3, 37.5, 30.5 and 22.2% of patients. A total, 9(15.3%), of cases died as a result of complications of COVID-19. Chest radiographs were reported in 72.9%(43/59) of cases that 94% demonstrated radiologic evidence of abnormality. CONCLUSION The results demonstrated that the most prevalent symptoms and signs were fever, dyspnea and cough. Moreover, most patients were males and hospitalized. The rate of mortality and high level of CRP, ALT/AST and ALP is similar within the non-immune suppressed and general population. However, early detection of high level of serum CRP, ALT/AST and ALP combined with a clinical COVID-19 symptom and finding of CT scan may be used as an index for the presence and severity of the disease.
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Affiliation(s)
- Pirouz Samidoust
- Razi Clinical Research Development Unit, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Hamed Nikoupour
- Shiraz Transplant Center, Abu Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hossein Hemmati
- Razi Clinical Research Development Unit, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Aryan Samidoust
- Razi Clinical Research Development Unit, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran
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16
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Karruli A, Spiezia S, Boccia F, Gagliardi M, Patauner F, Salemme A, Maiello C, Zampino R, Durante-Mangoni E. Effect of immunosuppression maintenance in solid organ transplant recipients with COVID-19: Systematic review and meta-analysis. Transpl Infect Dis 2021; 23:e13595. [PMID: 33641202 PMCID: PMC7995235 DOI: 10.1111/tid.13595] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Revised: 12/30/2020] [Accepted: 02/14/2021] [Indexed: 12/21/2022]
Abstract
Background The aim of this study was to assess the effect of continuing immune suppressive therapy in solid organ transplant recipients (SOTR) with coronavirus disease 2019 (COVID‐19). Methods Systematic review and meta‐analysis of data on 202 SOTR with COVID‐19, published as case reports or case series. We extracted clinical, hemato‐chemical, imaging, treatment, and outcome data. Results Most patients were kidney recipients (61.9%), males (68.8%), with median age of 57 years. The majority was on tacrolimus (73.5%) and mycophenolate (65.8%). Mortality was 18.8%, but an equal proportion was still hospitalized at last follow up. Immune suppressive therapy was withheld in 77.2% of patients, either partially or completely. Tacrolimus was continued in 50%. One third of survivors that continued immunosuppressants were on dual therapy plus steroids. None of those who continued immunosuppressants developed critical COVID‐19 disease. Age (OR 1.07, 95% CI 1‐1.11, P = .001) and lopinavir/ritonavir use (OR 3.3, 95%CI 1.2‐8.5, P = .013) were independent predictors of mortality while immunosuppression maintenance (OR 0.067, 95% CI 0.008‐0.558, P = .012) and tacrolimus continuation (OR 0.3, 95% CI 0.1‐0.7, P = .013) were independent predictors of survival. Conclusions Our data suggest that maintaining immune suppression might be safe in SOTR with moderate and severe COVID‐19. Specifically, receiving tacrolimus could be beneficial for COVID‐19 SOTR. Because of the quality of the available evidence, no definitive guidance on how to manage SOTR with COVID‐19 can be derived from our data.
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Affiliation(s)
- Arta Karruli
- Division of Internal Medicine, University of Campania 'L. Vanvitelli', Naples, Italy
| | - Serenella Spiezia
- Division of Internal Medicine, University of Campania 'L. Vanvitelli', Naples, Italy
| | - Filomena Boccia
- Division of Internal Medicine, University of Campania 'L. Vanvitelli', Naples, Italy
| | - Massimo Gagliardi
- Division of Internal Medicine, University of Campania 'L. Vanvitelli', Naples, Italy
| | - Fabian Patauner
- Division of Internal Medicine, University of Campania 'L. Vanvitelli', Naples, Italy
| | - Anna Salemme
- Division of Internal Medicine, University of Campania 'L. Vanvitelli', Naples, Italy
| | - Ciro Maiello
- Unit of Cardiac Surgery and Transplants, AORN Ospedali dei Colli-Monaldi Hospital, Naples, Italy
| | - Rosa Zampino
- Division of Internal Medicine, University of Campania 'L. Vanvitelli', Naples, Italy.,Unit of Infectious and Transplant Medicine, AORN Ospedali dei Colli-Monaldi Hospital, Naples, Italy
| | - Emanuele Durante-Mangoni
- Division of Internal Medicine, University of Campania 'L. Vanvitelli', Naples, Italy.,Unit of Infectious and Transplant Medicine, AORN Ospedali dei Colli-Monaldi Hospital, Naples, Italy
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17
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COVID-19 Among Patients With Hepatitis B or Hepatitis C: A Systematic Review. HEPATITIS MONTHLY 2021. [DOI: 10.5812/hepatmon.111617] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Context: Hepatic manifestations of Coronavirus Disease 2019 (COVID-19) are common among people living with Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV). Objectives: This systematic review aimed to summarize the evidence on COVID-19 patients living with HBV or HCV co-infections. Data Sources: We searched multiple electronic databases and preprint servers from December 1, 2019, to August 9, 2020. Study Selection: Studies were included if they reported quantitative empirical data on COVID-19 patients living with HBV or HCV co-infections. Data Extraction: Descriptive analyses were reported, and data were synthesized narratively. The quality assessment was completed using the Joanna Briggs Institute critical appraisal tools. Results: Out of the 941 uniquely identified records, 27 studies were included. Of the eligible studies, 232 COVID-19 patients were living with HBV and 22 were living with HCV. Most patients were male, and the mean age was 49.8 and 62.8 years in patients living with HBV and HCV, respectively. Among the reported cases of SARS-CoV-2-HBV co-infection, the proportions of death were 4.7% and 15% in cross-sectional and case series/report studies, respectively. The death proportion was 8.3% among the reported cases of SARS-CoV-2-HCV co-infection. Among COVID-19 patients, 34.1% and 76.2% reported at least one comorbidity besides HBV and HCV infections, mainly hypertension and type 2 diabetes mellitus. The most common COVID-19-related symptoms in both HBV and HCV groups were fever, cough, dyspnea, fatigue, and gastrointestinal symptoms. Conclusions: While understanding the pathogenesis of SARS-CoV-2 requires further investigations, the careful assessment of hepatic manifestations and chronic infections, such as HBV and HCV upon the admission of COVID-19 patients could help reduce multimorbidity among HBV or HCV patients and lead to more favorable health outcomes among them.
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Immunosuppressants. REACTIONS WEEKLY 2021. [PMCID: PMC7843889 DOI: 10.1007/s40278-021-90364-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
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