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Sharma P, Premkumar M, Guru RR, Sandhu A, Kajal K, De A, Rathi S, Verma N, Taneja S, Singh V, Duseja AK. Post COVID Condition and Long-Term COVID-19 Impact on Hepatic Decompensation and Survival in Cirrhosis: A Propensity Matched Observational Study. JGH Open 2025; 9:e70142. [PMID: 40135045 PMCID: PMC11932954 DOI: 10.1002/jgh3.70142] [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: 12/18/2024] [Revised: 03/04/2025] [Accepted: 03/09/2025] [Indexed: 03/27/2025]
Abstract
Aims Patients with cirrhosis are susceptible to decompensation events, including ascites, variceal bleeding (VB), hepatic encephalopathy, or death after COVID-19 infection. Patients may experience post-COVID condition (PCC) with multisystem involvement that persists for at least 2 months. Methods Hospitalized patients with cirrhosis and COVID-19 between January 2021 and January 2023 were assessed for decompensation events and mortality and compared to a propensity-matched cohort of cirrhosis and non-COVID-19 sepsis. Both groups were followed for outcomes over 1 year. Results Of 252 patients with Cirrhosis+ COVID-19 (73% men, aged 48.9 ± 13.7 years, 31%-diabetes, 44%-hypertension, 35%-alcohol-associated, 34.5%-metabolic dysfunction-associated steatotic liver disease; MASLD), 72 (28.6%) died in hospital and 180 (71.4%) recovered, similar to Cirrhosis+ non-COVID-sepsis (58/214, 27.1%). Finally,60 (33.3%) met criteria for PCC, 19 (10.5%) had no post COVID-19 sequelae and 101 (56.1%) patients died (N = 45) or were lost to follow up (N = 56). Late Mortality was higher in Cirrhosis+ COVID-19 than non-COVID-sepsis (56.1% vs. 35.3%, p = 0.026). Patients with PCC were aged 47.6 years, 63.3%-men, Charlson Comorbidity Index > 4 (51.7%), 45%-diabetes, 56.7%-hypertension, with 33.3%, 23.3%, and 43.3% in Child-Turcotte-Pugh class A, B and C, respectively. PCC symptoms included persistent dyspnea (34, 43%), cognitive impairment (20, 25.3%), and anxiety (47, 59.4%). On multivariable analysis, predictors of the development of PCC were baseline MELDNa (HR 1.12, 95% CI: 1.05-1.17, p < 0.001) and age (HR 0.9, 95% CI: 0.91-0.99, p = 0.012). Predictors of mortality following COVID-19 recovery were MELDNa (HR 1.03, 95% CI: 1.01-1.05, p = 0.008), age (HR 1.2, 95% CI: 1.1-1.5, p = 0.002) and hypertension (HR 1.63, 95% CI: 1.07-2.49, p = 0.025). Conclusion COVID-19 is associated with long-term mortality in cirrhosis even after recovery from respiratory infection. Long COVID is seen in a third of COVID-19 survivors in patients with cirrhosis.
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Affiliation(s)
- Prerna Sharma
- Department of HepatologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia
| | - Madhumita Premkumar
- Department of HepatologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia
| | - Rashmi Ranjan Guru
- Department of Hospital AdministrationPostgraduate Institute of Medical Education and ResearchChandigarhIndia
| | - Anchal Sandhu
- Department of HepatologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia
| | - Kamal Kajal
- Department of Anesthesia and Critical CarePostgraduate Institute of Medical Education and ResearchChandigarhIndia
| | - Arka De
- Department of HepatologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia
| | - Sahaj Rathi
- Department of HepatologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia
| | - Nipun Verma
- Department of HepatologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia
| | - Sunil Taneja
- Department of HepatologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia
| | - Virendra Singh
- Department of HepatologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia
| | - Ajay Kumar Duseja
- Department of HepatologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia
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Ismailova AG, Maslennikov RV, Zharkova MS, Ivashkin VT. Impact of Novel Coronavirus Infection on the Course and Prognosis of Cirrhosis. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2024; 33:65-80. [DOI: 10.22416/1382-4376-2023-33-6-65-80] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/26/2024]
Abstract
Аim: to investigate the impact of COVID-19 on the course and prognosis of cirrhosis.Materials and methods. This was a cohort study in patients with cirrhosis. We included patients with cirrhosis who underwent a medical examination at our center between September 2019 and March 2020. We determined which of these patients were infected with COVID-19, died of COVID-19, or died of cirrhosis complications within the follow-up period from April 2020 to September 2021. Thereafter, we conducted a second medical examination of these surviving patients with cirrhosis in September to December 2021.Results. Among the 226 patients included in the study, 57 had COVID-19, among which 19 patients who died of the disease. Acute-on-chronic liver failure (ACLF) developed in 16 (28.1 %) patients with cirrhosis and COVID-19, 13 (81.3 %) of whom died. One of the COVID-19 survivors eventually died of liver decompensation. Twenty patients who did not have COVID-19 died of complications of cirrhosis (ACLF) during the follow-up period. The mortality rate in patients who were infected with COVID-19 was higher than that in patients who were not infected (35.1 % vs. 14.2 %; p = 0.001). COVID-19 was an independent risk factor for death in patients with cirrhosis. No liver-specific factors predisposing to COVID-19 infection were identified. A more impaired liver function in the pre-pandemic medical examination was a predisposing factor for death in patients who had COVID-19. Patients who died of COVID-19 had better liver function in the pre-pandemic medical examination than patients without COVID-19 who died of complications of cirrhosis during the follow-up period. The liver-related mortality rate and the incidence of liver decompensation or bleeding from esophageal varices during the follow-up period were not significantly different between patients who recovered from COVID-19 and patients with cirrhosis who did not have COVID-19. Among the analyzed survivors, no significant changes were found in the main indicators of liver function after the follow-up period between patients with and without COVID-19, except for the prothrombin index, which was higher in patients after COVID-19.Conclusion. COVID-19 worsens the prognosis of patients with cirrhosis but does not substantially affect the course of cirrhosis after the recovery from this infection.
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Affiliation(s)
- A. G. Ismailova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - R. V. Maslennikov
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - M. S. Zharkova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - V. T. Ivashkin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
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Muzammil TS, Gangu K, Nasrullah A, Majeed H, Chourasia P, Bobba A, Shekhar R, Bartlett C, Sheikh AB. Thirty-Day readmissions among COVID-19 patients hospitalized during the early pandemic in the United States: Insights from the Nationwide Readmissions Database. Heart Lung 2023; 62:16-21. [PMID: 37290138 PMCID: PMC10244017 DOI: 10.1016/j.hrtlng.2023.05.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 05/19/2023] [Accepted: 05/22/2023] [Indexed: 06/10/2023]
Abstract
BACKGROUND Hospital readmissions are core indicators of the quality of health care provision. OBJECTIVE To understand factors associated with 30-day, all-cause hospital readmission rate for patients with COVID-19 in the United States during the early pandemic by utilizing the Nationwide Readmissions Database. METHODS This retrospective study characterized the 30-day, all-cause hospital readmission rate for patients with COVID-19 in the United States during the early pandemic by utilizing the Nationwide Readmissions Database. RESULTS The 30-day, all-cause hospital readmission rate in this population was 3.2%. We found the most common diagnoses at readmission to be sepsis, acute kidney injury, and pneumonia. Chronic alcoholic liver cirrhosis and congestive heart failure were prominent predictors of readmission among patients with COVID-19. Moreover, we found that younger patients and patients from economically disadvantaged backgrounds were at higher risk of 30-day readmission. Acute complications during index hospitalization, including acute coronary syndrome, congestive heart failure, acute kidney injury, mechanical ventilation, and renal replacement therapy, also increased the risk of 30-day readmission for patients with COVID-19. CONCLUSION Based on the results of our study, we advise clinicians to promptly recognize patients with COVID-19 who are at high risk of readmission, and to subsequently manage their underlying comorbidities, to institute timely discharge planning, and to allocate resources to underprivileged patients in order to decrease the risk of 30-day hospital readmissions.
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Affiliation(s)
| | - Karthik Gangu
- Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | - Adeel Nasrullah
- Division of Pulmonary and Critical Care, Allegheny Health Network, Pittsburg, PA, USA
| | - Harris Majeed
- Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
| | - Prabal Chourasia
- Department of Hospital Medicine, Mary Washington Hospital, Fredericksburg, VA, USA.
| | - Aneish Bobba
- Department of Medicine, John H. Stroger Jr. Hospital of Cook County, Chicago, IL, USA
| | - Rahul Shekhar
- Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
| | - Christopher Bartlett
- Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
| | - Abu Baker Sheikh
- Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
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Sherman Z, Wahid N, Wagner M, Soltani A, Rosenblatt R, Fortune B, Lucero C, Schoenfeld E, Brown R, Jesudian A. Integration of Cirrhosis Best Practices Into Electronic Medical Record Documentation Associated With Reduction in 30-Day Mortality Following Hospitalization. J Clin Gastroenterol 2023; 57:951-955. [PMID: 36730665 DOI: 10.1097/mcg.0000000000001787] [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] [Received: 06/03/2022] [Accepted: 09/24/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND Hospital admissions for patients with cirrhosis continue to increase. In New York City, 25% to 30% of hospitalized cirrhotics are readmitted within 30 days. Rehospitalization is associated with increased mortality, poor quality of life, and financial burden to patients, hospitals, and payers. Preventable readmissions are partially accounted for by a well-documented quality gap between evidence-based guidelines for cirrhosis management and real-world adherence to these recommendations. METHODS We performed a prospective cohort study that compared outcomes among cirrhotic patients admitted to 4 internal medicine teams over a 6-month period. An electronic medical record (EMR) note template that outlined best-practice measures for cirrhotics was developed. Inpatient providers on 2 teams were instructed to include it in daily progress notes and discharge summaries. The recommended practices included diagnostic paracentesis and diuretics for ascites, rifaximin, and lactulose for hepatic encephalopathy, beta blockers for esophageal varices, and antibiotic prophylaxis for spontaneous bacterial peritonitis. The remaining 2 teams continued the standard of care for cirrhotic patients. The primary outcome was 30-day readmissions. Secondary outcomes included in-hospital mortality, 30-day mortality, length of stay, and adherence to best-practice guidelines. RESULTS Over a 6-month period, 108 cirrhotic patients were admitted, 83 in the interventional group and 25 in the control group. MELD-Na scores on admission did not differ between the groups (20.1 vs. 21.1, P =0.56). Thirty-day readmissions were not significantly different between the interventional and control groups (19.3% vs. 24%, P =0.61). However, 30-day mortality was significantly lower in the interventional group (8.4% vs. 28%, P =0.01). There was no difference between the 2 groups in in-hospital mortality (4.8% vs. 0%, P =0.27), 90-day mortality (15.7% vs. 28.0%, P =0.17) or length of stay (10.2 vs. 12.6 d, P =0.34). Adherence to best-practice metrics was similar between the groups, except for rates of diagnostic paracentesis, which were higher in the interventional group (98% vs. 80%, P =0.01). CONCLUSION Implementation of an EMR note template with cirrhosis best practices was associated with lower 30-day mortality and higher rates of diagnostic paracentesis among admitted patients with cirrhosis. These findings suggest that the integration of best-practice measures into the EMR may improve outcomes in hospitalized cirrhotic patients. Larger studies are required to validate these findings.
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Affiliation(s)
- Zachary Sherman
- Division of Gastroenterology and Hepatology, New York Presbyterian Hospital/Weill Cornell Medical College
| | - Nabeel Wahid
- Department of Medicine, Memorial Sloan Kettering Cancer Center
| | - Michael Wagner
- Department of Medicine, Memorial Sloan Kettering Cancer Center
| | - Amin Soltani
- Division of Gastroenterology, Massachusetts General Hospital
| | - Russell Rosenblatt
- Center for Liver Disease and Transplantation, NewYork Presbyterian Hospital/Weill Cornell Medical College
| | - Brett Fortune
- Center for Liver Disease and Transplantation, NewYork Presbyterian Hospital/Weill Cornell Medical College
| | - Catherine Lucero
- Center for Liver Disease and Transplantation, NewYork Presbyterian Hospital/Weill Cornell Medical College
| | - Emily Schoenfeld
- Center for Liver Disease and Transplantation, NewYork Presbyterian Hospital/Weill Cornell Medical College
| | - Robert Brown
- Center for Liver Disease and Transplantation, NewYork Presbyterian Hospital/Weill Cornell Medical College
| | - Arun Jesudian
- Center for Liver Disease and Transplantation, NewYork Presbyterian Hospital/Weill Cornell Medical College
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Drácz B, Müller V, Takács I, Hagymási K, Dinya E, Miheller P, Szijártó A, Werling K. Hypocalcemia on Admission Is a Predictor of Disease Progression in COVID-19 Patients with Cirrhosis: A Multicenter Study in Hungary. Biomedicines 2023; 11:1541. [PMID: 37371636 DOI: 10.3390/biomedicines11061541] [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: 03/25/2023] [Revised: 05/22/2023] [Accepted: 05/23/2023] [Indexed: 06/29/2023] Open
Abstract
Hypocalcemia is a common condition in liver cirrhosis and is associated with the severity of SARS-CoV-2 infection. However, there is a lack of data demonstrating the prognostic value of hypocalcemia in COVID-19 patients with cirrhosis. This study aimed to evaluate the prognostic value of hypocalcemia for COVID-19 severity, mortality and its associations with abnormal liver function parameters. We selected 451 COVID-19 patients in this retrospective study and compared the laboratory findings of 52 COVID-19 patients with cirrhosis to those of 399 COVID-19 patients without cirrhosis. Laboratory tests measuring albumin-corrected total serum calcium were performed on admission, and the levels were monitored during hospitalization. The total serum calcium levels were significantly lower in cirrhosis cases (2.16 mmol/L) compared to those without cirrhosis (2.32 mmol/L). Multivariate analysis showed that hypocalcemia in COVID-19 patients with cirrhosis was a significant predictor of in-hospital mortality, with an OR of 4.871 (p < 0.05; 95% CI 1.566-15.146). ROC analysis showed the AUC value of total serum calcium was 0.818 (95% CI 0.683-0.953, p < 0.05), with a sensitivity of 88.3% and a specificity of 75%. The total serum calcium levels showed a significant negative correlation with the Child-Turcette-Pugh score (r = -0.400, p < 0.05). Hypocalcemia on admission was a significant prognostic factor of disease progression in COVID-19 patients with cirrhosis.
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Affiliation(s)
- Bálint Drácz
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, 1083 Budapest, Hungary
| | - Veronika Müller
- Department of Pulmonology, Semmelweis University, 1083 Budapest, Hungary
| | - István Takács
- Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary
| | - Krisztina Hagymási
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, 1083 Budapest, Hungary
| | - Elek Dinya
- Digital Health Department, Semmelweis University, 1083 Budapest, Hungary
| | - Pál Miheller
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, 1083 Budapest, Hungary
| | - Attila Szijártó
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, 1083 Budapest, Hungary
| | - Klára Werling
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, 1083 Budapest, Hungary
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Gananandan K, Mookerjee R. Letter to the Editor: Subjective and objective burden on providers from a multicenter app-based study of patients with cirrhosis and caregivers. Hepatol Commun 2023; 7:02009842-202305010-00024. [PMID: 37141502 PMCID: PMC10162785 DOI: 10.1097/hc9.0000000000000137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 03/03/2023] [Indexed: 05/06/2023] Open
Affiliation(s)
- Kohilan Gananandan
- Institute for Liver and Digestive Health, University College London, London, UK
| | - Rajeshwar Mookerjee
- Institute for Liver and Digestive Health, University College London, London, UK
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N, Denmark
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Liatsos GD. SARS-CoV-2 induced liver injury: Incidence, risk factors, impact on COVID-19 severity and prognosis in different population groups. World J Gastroenterol 2023; 29:2397-2432. [PMID: 37179584 PMCID: PMC10167898 DOI: 10.3748/wjg.v29.i16.2397] [Citation(s) in RCA: 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: 10/31/2022] [Revised: 02/17/2023] [Accepted: 04/07/2023] [Indexed: 04/24/2023] Open
Abstract
Liver is unlikely the key organ driving mortality in coronavirus disease 2019 (COVID-19) however, liver function tests (LFTs) abnormalities are widely observed mostly in moderate and severe cases. According to this review, the overall prevalence of abnormal LFTs in COVID-19 patients ranges from 2.5% to 96.8% worldwide. The geographical variability in the prevalence of underlying diseases is the determinant for the observed discrepancies between East and West. Multifactorial mechanisms are implicated in COVID-19-induced liver injury. Among them, hypercytokinemia with "bystander hepatitis", cytokine storm syndrome with subsequent oxidative stress and endotheliopathy, hypercoagulable state and immuno-thromboinflammation are the most determinant mechanisms leading to tissue injury. Liver hypoxia may also contribute under specific conditions, while direct hepatocyte injury is an emerging mechanism. Except for initially observed severe acute respiratory distress syndrome corona virus-2 (SARS-CoV-2) tropism for cholangiocytes, more recent cumulative data show SARS-CoV-2 virions within hepatocytes and sinusoidal endothelial cells using electron microscopy (EM). The best evidence for hepatocellular invasion by the virus is the identification of replicating SARS-CoV-2 RNA, S protein RNA and viral nucleocapsid protein within hepatocytes using in-situ hybridization and immunostaining with observed intrahepatic presence of SARS-CoV-2 by EM and by in-situ hybridization. New data mostly derived from imaging findings indicate possible long-term sequelae for the liver months after recovery, suggesting a post-COVID-19 persistent live injury.
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Affiliation(s)
- George D Liatsos
- Department of Internal Medicine, Hippokration General Hospital, Athens 11527, Attiki, Greece
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8
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Marginean CM, Cinteza E, Vasile CM, Popescu M, Biciusca V, Docea AO, Mitrut R, Popescu MS, Mitrut P. Features of Liver Injury in COVID-19 Pathophysiological, Biological and Clinical Particularities. GASTROENTEROLOGY INSIGHTS 2023; 14:156-169. [DOI: 10.3390/gastroent14020012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2025] Open
Abstract
The outbreak of the coronavirus pandemic in March 2020 has caused unprecedented pressure on public health and healthcare. The spectrum of COVID-19 onset is large, from mild cases with minor symptoms to severe forms with multi-organ dysfunction and death. In COVID-19, multiple organ damage has been described, including lung damage, acute kidney injury, liver damage, stroke, cardiovascular and digestive tract disorders. The aspects of liver injury are different, sometimes presenting with only a slight increase in liver enzymes, but sometimes with severe liver injury, leading to acute liver failure requiring liver transplantation. In patients with chronic liver disease, especially liver cirrhosis, immune dysfunction can increase the risk of infection. Immune dysfunction has a multifactorial physiopathological mechanism, implying a complement system and macrophage activation, lymphocyte and neutrophil activity dysfunction, and intestinal dysbiosis. This review aims to evaluate the most relevant studies published in the last years related to the etiopathogenetic, biochemical, and histological aspects of liver injury in patients diagnosed with COVID-19. Liver damage is more evident in patients with underlying chronic liver disease, with a significantly higher risk of developing severe outcomes of COVID-19 and death. Systemic inflammation, coagulation disorders, endothelial damage, and immune dysfunction explain the pathogenic mechanisms involved in impaired liver function. Although various mechanisms of action of SARS-CoV-2 on the liver cell have been studied, the impact of the direct viral effect on hepatocytes is not yet established.
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Affiliation(s)
- Cristina Maria Marginean
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Eliza Cinteza
- Pediatrics Department, University of Medicine and Pharmacy “Carol Davila”, 020021 Bucharest, Romania
- Department of Pediatric Cardiology, “Marie Curie” Emergency Children’s Hospital, 041451 Bucharest, Romania
| | - Corina Maria Vasile
- Department of Pediatric Cardiology, “Marie Curie” Emergency Children’s Hospital, 041451 Bucharest, Romania
- Department of Pediatric and Adult Congenital Cardiology, Bordeaux University Hospital, 33600 Pessac, France
| | - Mihaela Popescu
- Department of Endocrinology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Viorel Biciusca
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Anca Oana Docea
- Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Radu Mitrut
- Department of Cardiology, University and Emergency Hospital, 050098 Bucharest, Romania
| | - Marian Sorin Popescu
- Ph.D. School Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Paul Mitrut
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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Abstract
The coronavirus disease-2019 (COVID-19) pandemic has had a large impact on patients with chronic liver disease (CLD) and liver transplantation (LT) recipients. Patients with advanced CLD are at a significantly increased risk of poor outcomes in the setting of severe acute respiratory syndrome coronavirus 2 infection. The pandemic has also considerably altered the management and care that is provided to patients with CLD, pre-LT patients, and LT recipients. Vaccination against COVID-19 protects patients with CLD and LT recipients from adverse outcomes and is safe in these patients; however, vaccine efficacy may be reduced in LT recipients and other immunosuppressed patients.
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10
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Gupta T, Sharma H. COVID-19 and the liver: Are footprints still there? World J Gastroenterol 2023; 29:656-669. [PMID: 36742164 PMCID: PMC9896610 DOI: 10.3748/wjg.v29.i4.656] [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: 09/13/2022] [Revised: 10/13/2022] [Accepted: 11/21/2022] [Indexed: 01/20/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) hit the entire world as a global pandemic and soon became the most important concern for all patients with chronic diseases. An early trend in higher mortality in patients with acute respiratory distress attracted all researchers to closely monitor patients for the involvement of other systems. It soon became apparent that patients with chronic liver diseases are at increased risk of mortality given their cirrhosis-associated immune dysfunction. Additionally, liver function abnormalities were noted in patients with severe COVID-19. Profound cytokine storm, direct viral infection, drugs and reactivation of viral infections were causes of deranged liver functions. Here, we discuss the relation between COVID-19 and chronic liver disease, specifically cirrhosis, hepatitis B, hepatitis C, and non-alcoholic fatty liver disease (NAFLD), as well as the liver manifestations of COVID-19. The metabolic syndrome, obesity, diabetes mellitus and NAFLD were found to worsen outcome in different studies reported worldwide. Decompensated cirrhosis should be considered a risk factor for death and severe COVID-19. Recently, COVID-19 related cholangiopathy has also been reported with changes of secondary sclerosing cholangitis. The long-term persistence of viral antigens in gut epithelia raises concern regarding the future risk of autoimmune liver diseases.
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Affiliation(s)
- Tarana Gupta
- Department of Medicine, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak 124001, Haryana, India
| | - Hemant Sharma
- Department of Medicine, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak 124001, Haryana, India
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11
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Gananandan K, Phillips A, Chikhlia A, Old H, Sim SJY, Thakur N, Hussain I, Kazankov K, Mookerjee RP. Negative impact of the pandemic on hospital admissions, morbidity and early mortality for acute cirrhosis decompensation. BMJ Open Gastroenterol 2023; 10:bmjgast-2022-001071. [PMID: 36650007 PMCID: PMC9853150 DOI: 10.1136/bmjgast-2022-001071] [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: 11/14/2022] [Accepted: 01/03/2023] [Indexed: 01/19/2023] Open
Abstract
INTRODUCTION The global pandemic has diverted resources away from management of chronic diseases, including cirrhosis. While there is increasing knowledge on COVID-19 infection in liver cirrhosis, little is described on the impact of the pandemic on decompensated cirrhosis admissions and outcomes, which was the aim of this study. METHODS A single-centre, retrospective study, evaluated decompensated cirrhosis admissions to a tertiary London hepatology and transplantation centre, from October 2018 to February 2021. Patients were included if they had an admission with cirrhosis decompensation defined as new-onset jaundice or ascites, infection, encephalopathy, portal hypertensive bleeding or renal dysfunction. RESULTS The average number of admissions stayed constant between the pre-COVID-19 (October 2018-February 2020) and COVID-19 periods (March 2020-February 2021). Patients transferred in from secondary centres had consistently higher severity scores during the COVID-19 period (UK Model for End-Stage Liver Disease 58 vs 54; p=0.007, Model for End-Stage Liver Disease-Sodium 22 vs 18; p=0.006, EF-CLIF Acute Decompensation (AD) score 55.0 vs 51.0; p=0.055). Of those admitted to the intensive care without acute-on-chronic liver failure, there was a significant increase in AD scores during the COVID-19 period (58 vs 48, p=0.009). In addition, there was a trend towards increased hospital readmission rates during the COVID-19 period (29.5% vs 21.5%, p=0.067). When censored at 30 days, early mortality postdischarge was significantly higher during the COVID-19 period (p<0.001) with a median time to death of 35 days compared with 62 days pre-COVID-19. DISCUSSION This study provides a unique perspective on the impact that the global pandemic had on decompensated cirrhosis admissions. The findings of increased early mortality and readmissions, and higher AD scores on ICU admission, highlight the need to maintain resourcing for high-level hepatology care and follow-up, in spite of other disease pressures.
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Affiliation(s)
- Kohilan Gananandan
- University College London Institute for Liver and Digestive Health, London, UK
| | - Alexandra Phillips
- University College London Institute for Liver and Digestive Health, London, UK
| | | | - Hannah Old
- Royal Free London NHS Foundation Trust, London, UK
| | | | - Niharika Thakur
- University College London Institute for Liver and Digestive Health, London, UK
| | - Ishrat Hussain
- University College London Institute for Liver and Digestive Health, London, UK
| | - Konstantin Kazankov
- University College London Institute for Liver and Digestive Health, London, UK,Aarhus University Hospital Department of Hepatology and Gastroenterology, Aarhus, Midtjylland, Denmark
| | - Rajeshwar P Mookerjee
- University College London Institute for Liver and Digestive Health, London, UK .,Aarhus University Hospital Department of Hepatology and Gastroenterology, Aarhus, Midtjylland, Denmark
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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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13
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Drácz B, Müller V, Takács I, Hagymási K, Dinya E, Miheller P, Szijártó A, Werling K. Effectiveness of COVID-19 Vaccination with mRNA Vaccines for Patients with Cirrhosis in Hungary: Multicentre Matched Cohort Study. Vaccines (Basel) 2022; 11:vaccines11010050. [PMID: 36679899 PMCID: PMC9861308 DOI: 10.3390/vaccines11010050] [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: 11/26/2022] [Revised: 12/22/2022] [Accepted: 12/23/2022] [Indexed: 12/28/2022] Open
Abstract
Patients with cirrhosis are vulnerable to hepatic decompensation events and death following COVID-19 infection. Therefore, primary vaccination with COVID-19 vaccines is fundamental to reducing the risk of COVID-19 related deaths in patients with cirrhosis. However, limited data are available about the effectiveness of mRNA vaccines compared to other vaccines. The aim of our study was to investigate the efficacy of mRNA vaccines versus other vaccines in cirrhosis. In this retrospective study, we compared clinical characteristics and vaccine effectiveness of 399 COVID-19 patients without cirrhosis (GROUP A) to 52 COVID-19 patients with cirrhosis (GROUP B). 54 hospitalised cirrhosis controls without COVID-19 (GROUP C) were randomly sampled 1:1 and matched by gender and age. Of the cirrhosis cases, we found no difference (p = 0.76) in mortality rates in controls without COVID-19 (11.8%) compared to those with COVID-19 (9.6%). However, COVID-19 patients with cirrhosis were associated with higher rates of worsening hepatic encephalopathy, ascites and esophageal varices. Patients with cirrhosis receiving mRNA vaccines had significantly better survival rates compared to viral vector or inactivated vaccines. Primary vaccination with the BNT162b2 vaccine was the most effective in preventing acute hepatic decompensating events, COVID-19 infection requiring hospital admission and in-hospital mortality.
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Affiliation(s)
- Bálint Drácz
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, 1083 Budapest, Hungary
- Correspondence:
| | - Veronika Müller
- Department of Pulmonology, Semmelweis University, 1083 Budapest, Hungary
| | - István Takács
- Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary
| | - Krisztina Hagymási
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, 1083 Budapest, Hungary
| | - Elek Dinya
- Digital Health Department, Semmelweis University, 1083 Budapest, Hungary
| | - Pál Miheller
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, 1083 Budapest, Hungary
| | - Attila Szijártó
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, 1083 Budapest, Hungary
| | - Klára Werling
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, 1083 Budapest, Hungary
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14
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Domovitz T, Ayoub S, Werbner M, Alter J, Izhaki Tavor L, Yahalom-Ronen Y, Tikhonov E, Meirson T, Maman Y, Paran N, Israely T, Dessau M, Gal-Tanamy M. HCV Infection Increases the Expression of ACE2 Receptor, Leading to Enhanced Entry of Both HCV and SARS-CoV-2 into Hepatocytes and a Coinfection State. Microbiol Spectr 2022; 10:e0115022. [PMID: 36314945 PMCID: PMC9769977 DOI: 10.1128/spectrum.01150-22] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 09/28/2022] [Indexed: 11/09/2022] Open
Abstract
Recent studies suggest the enhancement of liver injury in COVID-19 patients infected with Hepatitis C virus (HCV). Hepatocytes express low levels of angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor, raising the possibility of HCV-SARS-CoV-2 coinfection in the liver. This work aimed to explore whether HCV and SARS-CoV-2 coinfect hepatocytes and the interplay between these viruses. We demonstrate that SARS-CoV-2 coinfects HCV-infected Huh7.5 (Huh7.5HCV) cells. Both viruses replicated efficiently in the coinfected cells, with HCV replication enhanced in coinfected compared to HCV-mono-infected cells. Strikingly, Huh7.5HCV cells were eight fold more susceptible to SARS-CoV-2 pseudoviruses than naive Huh7.5 cells, suggesting enhanced SARS-CoV-2 entry into HCV-preinfected hepatocytes. In addition, we observed increased binding of spike receptor-binding domain (RBD) protein to Huh7.5HCV cells, as well as enhanced cell-to-cell fusion of Huh7.5HCV cells with spike-expressing Huh7.5 cells. We explored the mechanism of enhanced SARS-CoV-2 entry and identified an increased ACE2 mRNA and protein levels in Huh7.5HCV cells, primary hepatocytes, and in data from infected liver biopsies obtained from database. Importantly, higher expression of ACE2 increased HCV infection by enhancing its binding to the host cell, underscoring its role in the HCV life cycle as well. Transcriptome analysis revealed that shared host signaling pathways were induced in HCV-SARS-CoV-2 coinfection. This study revealed complex interactions between HCV and SARS-CoV-2 infections in hepatocytes, which may lead to the increased liver damage recently reported in HCV-positive COVID-19 patients. IMPORTANCE Here, we provide the first experimental evidence for the coexistence of SARS-CoV-2 infection with HCV, and the interplay between them. The study revealed a complex relationship of enhancement between the two viruses, where HCV infection increased the expression of the SARS-CoV-2 entry receptor ACE2, thus facilitating SARS-CoV-2 entry, and potentially, also HCV entry. Thereafter, SARS-CoV-2 infection enhanced HCV replication in hepatocytes. This study may explain the aggravation of liver damage that was recently reported in COVID-19 patients with HCV coinfection and suggests preinfection with HCV as a risk factor for severe COVID-19. Moreover, it highlights the possible importance of HCV treatment for coinfected patients. In a broader view, these findings emphasize the importance of identifying coinfecting pathogens that increase the risk of SARS-CoV-2 infection and that may accelerate COVID-19-related co-morbidities.
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Affiliation(s)
- Tom Domovitz
- Molecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Samer Ayoub
- Molecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Michal Werbner
- Molecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Joel Alter
- The Laboratory of Structural Biology of Infectious Diseases, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Lee Izhaki Tavor
- The Laboratory of Structural Biology of Infectious Diseases, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Yfat Yahalom-Ronen
- Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel
| | - Evgeny Tikhonov
- The Lab of Genomic Instability and Cancer, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Tomer Meirson
- The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
- Davidoff Cancer Center, Rabin Medical Center-Beilinson Hospital, Petah Tikva, Israel
| | - Yaakov Maman
- The Lab of Genomic Instability and Cancer, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Nir Paran
- Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel
| | - Tomer Israely
- Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel
| | - Moshe Dessau
- The Laboratory of Structural Biology of Infectious Diseases, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Meital Gal-Tanamy
- Molecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
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15
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Abstract
Knowledge on SARS-CoV-2 infection and its resultant COVID-19 in liver diseases has rapidly increased during the pandemic. Hereby, we review COVID-19 liver manifestations and pathophysiological aspects related to SARS-CoV-2 infection in patients without liver disease as well as the impact of COVID-19 in patients with chronic liver disease (CLD), particularly cirrhosis and liver transplantation (LT). SARS-CoV-2 infection has been associated with overt proinflammatory cytokine profile, which probably contributes substantially to the observed early and late liver abnormalities. CLD, particularly decompensated cirrhosis, should be regarded as a risk factor for severe COVID-19 and death. LT was impacted during the pandemic, mainly due to concerns regarding donation and infection in recipients. However, LT did not represent a risk factor per se of worse outcome. Even though scarce, data regarding COVID-19 specific therapy in special populations such as LT recipients seem promising. COVID-19 vaccine-induced immunity seems impaired in CLD and LT recipients, advocating for a revised schedule of vaccine administration in this population.
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Affiliation(s)
- Jean-François Dufour
- Hepatology, Department of Biomedical Research, University of Bern, Bern, Switzerland
| | - Thomas Marjot
- Oxford Liver Unit, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK
- Nuffield Department of Medicine, Translational Gastroenterology Unit, University of Oxford, Oxford, UK
| | - Chiara Becchetti
- Department of Hepatology and Gastroenterology, ASST Grande Ospedale Metropolitano Niguarda, Bern, Italy
- Department of Visceral Surgery and Medicine, Inselspital, University Hospital of Bern, Bern, Switzerland
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University Innsbruck, Innsbruck, Austria
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16
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Elnaggar M, Abomhya A, Elkhattib I, Dawoud N, Doshi R. COVID-19 and liver diseases, what we know so far. World J Clin Cases 2022; 10:3969-3980. [PMID: 35665122 PMCID: PMC9131221 DOI: 10.12998/wjcc.v10.i13.3969] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 10/15/2021] [Accepted: 03/26/2022] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) pneumonia outbreak started in December 2019. On March 12, 2020, the World Health Organization (WHO) declared that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitutes a pandemic, and as of May 2021, SARS-CoV-2 has infected over 167.3 million patients, including 3.4 million deaths, reported to WHO. In this review, we will focus on the relationship between SARS-CoV-2 infection and the liver. We will discuss how chronic liver diseases affect the COVID-19 disease course and outcomes. We will also discuss the SARS-CoV-2 effects on the liver, mechanisms of acute liver injury, and potential management plans.
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Affiliation(s)
- Mohamed Elnaggar
- Department of Internal Medicine, University of Nevada Reno School of Medicine, Reno, NV 89052, United States
| | - Ahmed Abomhya
- Department of Internal Medicine, The Brooklyn Hospital Center, Brooklyn, NY 11200, United States
| | - Ismail Elkhattib
- Department of Internal Medicine, University of Connecticut, Farmington, CT 06030, United States
| | - Nabila Dawoud
- Department of Internal Medicine, University of Kentucky, Lexington, KY 40508, United States
| | - Rajkumar Doshi
- Department of Cardiology, St Joseph's University Medical Center, Paterson, NJ 07503, United States
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17
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Kirkegaard C, Falcó-Roget A, Sánchez-Montalvá A, Valls Á, Clofent D, Campos-Varela I, García-García S, Leguízamo LM, Sellarès-Nadal J, Eremiev S, Villamarín M, Marzo B, Almirante B, Len Ò. Incidence and risk factors for early readmission after hospitalization for SARS-CoV-2 infection: results from a retrospective cohort study. Infection 2022; 50:371-380. [PMID: 34331263 PMCID: PMC8323963 DOI: 10.1007/s15010-021-01662-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 07/05/2021] [Indexed: 01/08/2023]
Abstract
PURPOSE We aim to assess risk factors related to early readmission in previous hospitalized patients with COVID-19. METHODS We analyzed a retrospective cohort of patients with laboratory-confirmed COVID-19 admitted to Vall d'Hebron University Hospital, Barcelona, Spain. Early readmission was defined as the need for hospitalization within a period of 60 days after discharge. A descriptive analysis of the readmission was performed, including hospitalization outcome. We also performed a multivariate logistic regression to define risk factors for readmission RESULTS: A total of 629 patients were followed up during 60 days with a readmission cumulative incidence of 5.4% (34 out of 629) and an incidence rate of 0.034 person-years. Main reasons for readmission were respiratory worsening (13, 38.2%), decompensation of previous disease (12, 35.3%) or infectious complications (6, 17.6%). Median time to readmission was 12 days (interquartile range 7-33 days). Prior diagnosis of heart failure (OR 4.09; 95% CI 1.35-12.46; p = 0.013), length of stay during index admission greater than 13 days (OR 2.72; 95% CI 1.21-6.12; p = 0.015), treatment with corticosteroids (OR 2.39; 95% CI 1.01-5.70; p = 0.049) and developing pulmonary thromboembolism (OR 11.59; 95% CI 2.89-46.48; p = 0.001) were the risk factors statistically associated with early readmission. CONCLUSION Readmission cumulative incidence was 5.4%. Those patients with prior diagnosis of heart failure, length of stay greater than 13 days, treated with corticosteroids or who developed pulmonary thromboembolism might benefit from close monitoring after being discharged.
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Affiliation(s)
- Cristina Kirkegaard
- Infectious Diseases Department, University Hospital Vall d'Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Anna Falcó-Roget
- Infectious Diseases Department, University Hospital Vall d'Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Adrián Sánchez-Montalvá
- Infectious Diseases Department, University Hospital Vall d'Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain
- Programa de Salut Internacional de Catalunya del Institut Català de la Salut (PROSICS), Barcelona, Spain
| | - Ángel Valls
- Internal Medicine Department, University Hospital Vall d'Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - David Clofent
- Pneumology Department, University Hospital Vall d'Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Isabel Campos-Varela
- Internal Medicine-Hepatology Department, University Hospital Vall d'Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Sonia García-García
- Pharmacy Department, University Hospital Vall d'Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Lina María Leguízamo
- Clinical Pharmacology Department, University Hospital Vall d'Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Júlia Sellarès-Nadal
- Infectious Diseases Department, University Hospital Vall d'Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Simeon Eremiev
- Infectious Diseases Department, University Hospital Vall d'Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Miguel Villamarín
- Infectious Diseases Department, University Hospital Vall d'Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Blanca Marzo
- Infectious Diseases Department, University Hospital Vall d'Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Benito Almirante
- Infectious Diseases Department, University Hospital Vall d'Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain
- Spanish Network for the Study of Infectious Diseases (REIPI), Barcelona, Spain
| | - Òscar Len
- Infectious Diseases Department, University Hospital Vall d'Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain.
- Spanish Network for the Study of Infectious Diseases (REIPI), Barcelona, Spain.
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18
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Neuman MG, Seitz HK, Teschke R, Malnick S, Johnson-Davis KL, Cohen LB, German A, Hohmann N, Moreira B, Moussa G, Opris M. Molecular, Viral and Clinical Features of Alcohol- and Non-Alcohol-Induced Liver Injury. Curr Issues Mol Biol 2022; 44:1294-1315. [PMID: 35723310 PMCID: PMC8947098 DOI: 10.3390/cimb44030087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 03/06/2022] [Accepted: 03/14/2022] [Indexed: 01/08/2023] Open
Abstract
Hepatic cells are sensitive to internal and external signals. Ethanol is one of the oldest and most widely used drugs in the world. The focus on the mechanistic engine of the alcohol-induced injury has been in the liver, which is responsible for the pathways of alcohol metabolism. Ethanol undergoes a phase I type of reaction, mainly catalyzed by the cytoplasmic enzyme, alcohol dehydrogenase (ADH), and by the microsomal ethanol-oxidizing system (MEOS). Reactive oxygen species (ROS) generated by cytochrome (CYP) 2E1 activity and MEOS contribute to ethanol-induced toxicity. We aimed to: (1) Describe the cellular, pathophysiological and clinical effects of alcohol misuse on the liver; (2) Select the biomarkers and analytical methods utilized by the clinical laboratory to assess alcohol exposure; (3) Provide therapeutic ideas to prevent/reduce alcohol-induced liver injury; (4) Provide up-to-date knowledge regarding the Corona virus and its affect on the liver; (5) Link rare diseases with alcohol consumption. The current review contributes to risk identification of patients with alcoholic, as well as non-alcoholic, liver disease and metabolic syndrome. Additional prevalence of ethnic, genetic, and viral vulnerabilities are presented.
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Affiliation(s)
- Manuela G. Neuman
- In Vitro Drug Safety and Biotechnology and the Department of Pharmacology and Toxicology, Temerity Faculty of Medicine, University of Toronto, Toronto, ON M5G 1L5, Canada; (G.M.); (M.O.)
- Correspondence:
| | - Helmut K. Seitz
- Centre of Liver and Alcohol Diseases, Ethianum Clinic and Department of Clinical Pharmacology and Pharmacoepidemiology, Faculty of Medicine, University of Heidelberg, 69115 Heidelberg, Germany; (H.K.S.); (N.H.); (B.M.)
| | - Rolf Teschke
- Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Hanau, Academic Teaching Hospital of the Medical Faculty, Goethe University Frankfurt/Main, 60323 Frankfurt, Germany;
| | - Stephen Malnick
- Department of Internal Medicine C. Kaplan Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Rehovot 76100, Israel; (S.M.); (A.G.)
| | - Kamisha L. Johnson-Davis
- Department of Pathology, University of Utah Health Sciences Centre and Division of Toxicology, ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT 84115, USA;
| | - Lawrence B. Cohen
- Division of Gastroenterology, Sunnybrook Health Sciences Centre and Department of Medicine, Temerity Faculty of Medicine, University of Toronto, Toronto, ON M4N 3N5, Canada;
| | - Anit German
- Department of Internal Medicine C. Kaplan Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Rehovot 76100, Israel; (S.M.); (A.G.)
| | - Nicolas Hohmann
- Centre of Liver and Alcohol Diseases, Ethianum Clinic and Department of Clinical Pharmacology and Pharmacoepidemiology, Faculty of Medicine, University of Heidelberg, 69115 Heidelberg, Germany; (H.K.S.); (N.H.); (B.M.)
| | - Bernhardo Moreira
- Centre of Liver and Alcohol Diseases, Ethianum Clinic and Department of Clinical Pharmacology and Pharmacoepidemiology, Faculty of Medicine, University of Heidelberg, 69115 Heidelberg, Germany; (H.K.S.); (N.H.); (B.M.)
| | - George Moussa
- In Vitro Drug Safety and Biotechnology and the Department of Pharmacology and Toxicology, Temerity Faculty of Medicine, University of Toronto, Toronto, ON M5G 1L5, Canada; (G.M.); (M.O.)
| | - Mihai Opris
- In Vitro Drug Safety and Biotechnology and the Department of Pharmacology and Toxicology, Temerity Faculty of Medicine, University of Toronto, Toronto, ON M5G 1L5, Canada; (G.M.); (M.O.)
- Family Medicine Clinic CAR, 010362 Bucharest, Romania
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19
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Corrao G, Rea F, Carle F, Scondotto S, Allotta A, Lepore V, D'Ettorre A, Tanzarella C, Vittori P, Abena S, Iommi M, Spazzafumo L, Ercolanoni M, Blaco R, Carbone S, Giordani C, Manfellotto D, Galli M, Mancia G. Stratification of the risk of developing severe or lethal Covid-19 using a new score from a large Italian population: a population-based cohort study. BMJ Open 2021; 11:e053281. [PMID: 34794995 PMCID: PMC8602929 DOI: 10.1136/bmjopen-2021-053281] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVES To develop a population-based risk stratification model (COVID-19 Vulnerability Score) for predicting severe/fatal clinical manifestations of SARS-CoV-2 infection, using the multiple source information provided by the healthcare utilisation databases of the Italian National Health Service. DESIGN Retrospective observational cohort study. SETTING Population-based study using the healthcare utilisation database from five Italian regions. PARTICIPANTS Beneficiaries of the National Health Service, aged 18-79 years, who had the residentship in the five participating regions. Residents in a nursing home were not included. The model was built from the 7 655 502 residents of Lombardy region. MAIN OUTCOME MEASURE The score included gender, age and 29 conditions/diseases selected from a list of 61 conditions which independently predicted the primary outcome, that is, severe (intensive care unit admission) or fatal manifestation of COVID-19 experienced during the first epidemic wave (until June 2020). The score performance was validated by applying the model to several validation sets, that is, Lombardy population (second epidemic wave), and the other four Italian regions (entire 2020) for a total of about 15.4 million individuals and 7031 outcomes. Predictive performance was assessed by discrimination (areas under the receiver operating characteristic curve) and calibration (plot of observed vs predicted outcomes). RESULTS We observed a clear positive trend towards increasing outcome incidence as the score increased. The areas under the receiver operating characteristic curve of the COVID-19 Vulnerability Score ranged from 0.85 to 0.88, which compared favourably with the areas of generic scores such as the Charlson Comorbidity Score (0.60). A remarkable performance of the score on the calibration of observed and predicted outcome probability was also observed. CONCLUSIONS A score based on data used for public health management accurately predicted the occurrence of severe/fatal manifestations of COVID-19. Use of this score may help health decision-makers to more accurately identify high-risk citizens who need early preventive or treatment interventions.
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Affiliation(s)
- Giovanni Corrao
- Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy
- National Centre for Healthcare Research and Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy
| | - Federico Rea
- Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy
- National Centre for Healthcare Research and Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy
| | - Flavia Carle
- National Centre for Healthcare Research and Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy
- Center of Epidemiology and Biostatistics, Polytechnic University of Marche, Ancona, Italy
| | - Salvatore Scondotto
- National Centre for Healthcare Research and Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy
- Department of Health Services and Epidemiological Observatory, Regional Health Authority of Sicily, Palermo, Italy
| | - Alessandra Allotta
- Department of Health Services and Epidemiological Observatory, Regional Health Authority of Sicily, Palermo, Italy
| | - Vito Lepore
- Regional Health Agency of Puglia, Bari, Italy
| | | | | | | | | | - Marica Iommi
- Center of Epidemiology and Biostatistics, Polytechnic University of Marche, Ancona, Italy
| | - Liana Spazzafumo
- National Centre for Healthcare Research and Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy
- Regional Health Agency of Marche, Ancona, Italy
| | | | | | - Simona Carbone
- Department of Health Planning, Italian Health Ministry, Rome, Italy
| | | | - Dario Manfellotto
- Department of Internal Medicine, Hospital Fatebenefratelli, Rome, Italy
| | - Massimo Galli
- Institute of Tropical and Infectious Diseases, University of Milan L Sacco Hospital, Milan, Italy
| | - Giuseppe Mancia
- University of Milano-Bicocca, Milan, Italy
- Policlinico di Monza, Monza, Italy
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20
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Ramzi ZS. Hospital readmissions and post-discharge all-cause mortality in COVID-19 recovered patients; A systematic review and meta-analysis. Am J Emerg Med 2021; 51:267-279. [PMID: 34781153 PMCID: PMC8570797 DOI: 10.1016/j.ajem.2021.10.059] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 10/27/2021] [Accepted: 10/28/2021] [Indexed: 02/08/2023] Open
Abstract
OBJECTIVE The present study aimed to perform a systematic review and meta-analysis on the prevalence of one-year hospital readmissions and post-discharge all-cause mortality in recovered COVID-19 patients. Moreover, the country-level prevalence of the outcomes was investigated. METHODS An extensive search was performed in Medline (PubMed), Embase, Scopus, and Web of Science databases until the end of August 3rd, 2021. A manual search was also performed in Google and Google Scholar search engines. Cohort and cross-sectional studies were included. Two independent reviewers screened the papers, collected data, and assessed the risk of bias and level of evidence. Any disagreement was resolved through discussion. RESULTS 91 articles were included. 48 studies examined hospital readmissions; nine studies assessed post-discharge all-cause mortality, and 34 studies examined both outcomes. Analyses showed that the prevalence of hospital readmissions during the first 30 days, 90 days, and one-year post-discharge were 8.97% (95% CI: 7.44, 10.50), 9.79% (95% CI: 8.37, 11.24), and 10.34% (95% CI: 8.92, 11.77), respectively. The prevalence of post-discharge all-cause mortality during the 30 days, 90 days and one-year post-discharge was 7.87% (95% CI: 2.78, 12.96), 7.63% (95% CI: 4.73, 10.53) and 7.51% (95% CI, 5.30, 9.72), respectively. 30-day hospital readmissions and post-discharge mortality were 8.97% and 7.87%, respectively. The highest prevalence of hospital readmissions was observed in Germany (15.5%), Greece (15.5%), UK (13.5%), Netherlands (11.7%), China (10.8%), USA (10.0%) and Sweden (9.9%). In addition, the highest prevalence of post-discharge all-cause mortality belonged to Italy (12.7%), the UK (11.8%), and Iran (9.2%). Sensitivity analysis showed that the prevalence of one-year hospital readmissions and post-discharge all-cause mortality in high-quality studies were 10.38% and 4.00%, respectively. CONCLUSION 10.34% of recovered COVID-19 patients required hospital readmissions after discharge. Most cases of hospital readmissions and mortality appear to occur within 30 days after discharge. The one-year post-discharge all-cause mortality rate of COVID-19 patients is 7.87%, and the majority of patients' readmission and mortality happens within the first 30 days post-discharge. Therefore, a 30-day follow-up program and patient tracking system for discharged COVID-19 patients seems necessary.
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Affiliation(s)
- Zhian Salah Ramzi
- Department of Family and Community Medicine, College of Medicine, University of Sulaimani, Sulaimani, Iraq.
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21
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Hutchison AL, Pillai A. The effect of COVID-19 on liver transplantation: impact, practice patterns, therapeutics, and next steps. Curr Opin Organ Transplant 2021; 26:339-345. [PMID: 33938470 DOI: 10.1097/mot.0000000000000883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE OF REVIEW To assess the impact of coronavirus disease 2019 (COVID-19) and the pandemic on liver transplant candidates, recipients, and donors, and review guidelines and recommendations for integrating COVID-19 therapies into current practice. RECENT FINDINGS COVID-19 has high morbidity and mortality for transplant candidates; interestingly, posttransplant comorbidities play a larger role than immunosuppression status. COVID-19 therapies and vaccinations are well tolerated in pre and postliver transplant patients with few exceptions, although further research is needed regarding effectiveness in this patient population. Provider practice patterns should evolve to minimize contagion during the current pandemic and prepare for an increase in liver disease due to after-shocks of missed diagnosis and progression of liver disease. SUMMARY COVID-19 has spurred new research and technologies to ensure the safety of liver transplant candidates, recipients, and donors, and most COVID-19 therapies are safe in this patient population. Further work needs to be done regarding the use of COVID-19 positive organs and the efficacy of vaccines in the transplant population.
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Affiliation(s)
| | - Anjana Pillai
- Department of Internal Medicine, Center for Liver Diseases, University of Chicago Medicine, Chicago, IL, USA
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22
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Marjot T, Webb GJ, Barritt AS, Moon AM, Stamataki Z, Wong VW, Barnes E. COVID-19 and liver disease: mechanistic and clinical perspectives. Nat Rev Gastroenterol Hepatol 2021; 18:348-364. [PMID: 33692570 PMCID: PMC7945972 DOI: 10.1038/s41575-021-00426-4] [Citation(s) in RCA: 251] [Impact Index Per Article: 62.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/04/2021] [Indexed: 02/06/2023]
Abstract
Our understanding of the hepatic consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its resultant coronavirus disease 2019 (COVID-19) has evolved rapidly since the onset of the pandemic. In this Review, we discuss the hepatotropism of SARS-CoV-2, including the differential expression of viral receptors on liver cell types, and we describe the liver histology features present in patients with COVID-19. We also provide an overview of the pattern and relevance of abnormal liver biochemistry during COVID-19 and present the possible underlying direct and indirect mechanisms for liver injury. Furthermore, large international cohorts have been able to characterize the disease course of COVID-19 in patients with pre-existing chronic liver disease. Patients with cirrhosis have particularly high rates of hepatic decompensation and death following SARS-CoV-2 infection and we outline hypotheses to explain these findings, including the possible role of cirrhosis-associated immune dysfunction. This finding contrasts with outcome data in pharmacologically immunosuppressed patients after liver transplantation who seem to have comparatively better outcomes from COVID-19 than those with advanced liver disease. Finally, we discuss the approach to SARS-CoV-2 vaccination in patients with cirrhosis and after liver transplantation and predict how changes in social behaviours and clinical care pathways during the pandemic might lead to increased liver disease incidence and severity.
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Affiliation(s)
- Thomas Marjot
- Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, UK.
| | - Gwilym J Webb
- Cambridge Liver Unit, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, UK
| | - Alfred S Barritt
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
| | - Andrew M Moon
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
| | - Zania Stamataki
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Vincent W Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Eleanor Barnes
- Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, UK.
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