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Zhao SW, Li YM, Li YL, Su C. Liver injury in COVID-19: Clinical features, potential mechanisms, risk factors and clinical treatments. World J Gastroenterol 2023; 29:241-256. [PMID: 36687127 PMCID: PMC9846943 DOI: 10.3748/wjg.v29.i2.241] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 11/11/2022] [Accepted: 12/08/2022] [Indexed: 01/06/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has been a serious threat to global health for nearly 3 years. In addition to pulmonary complications, liver injury is not uncommon in patients with novel COVID-19. Although the prevalence of liver injury varies widely among COVID-19 patients, its incidence is significantly increased in severe cases. Hence, there is an urgent need to understand liver injury caused by COVID-19. Clinical features of liver injury include detectable liver function abnormalities and liver imaging changes. Liver function tests, computed tomography scans, and ultrasound can help evaluate liver injury. Risk factors for liver injury in patients with COVID-19 include male sex, preexisting liver disease including liver transplantation and chronic liver disease, diabetes, obesity, and hypertension. To date, the mechanism of COVID-19-related liver injury is not fully understood. Its pathophysiological basis can generally be explained by systemic inflammatory response, hypoxic damage, ischemia-reperfusion injury, and drug side effects. In this review, we systematically summarize the existing literature on liver injury caused by COVID-19, including clinical features, underlying mechanisms, and potential risk factors. Finally, we discuss clinical management and provide recommendations for the care of patients with liver injury.
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Affiliation(s)
- Shu-Wu Zhao
- Department of Anesthesiology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, Hunan Province, China
| | - Yi-Ming Li
- School of Basic Medical Science, Naval Medical University/Second Military University, Shanghai 200433, China
| | - Yi-Lin Li
- Department of Pathology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, Hunan Province, China
| | - Chen Su
- Department of Anesthesiology and Pain, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, Hunan Province, China
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Hu WS, Jiang FY, Shu W, Zhao R, Cao JM, Wang DP. Liver injury in COVID-19: A minireview. World J Gastroenterol 2022; 28:6716-6731. [PMID: 36620342 PMCID: PMC9813934 DOI: 10.3748/wjg.v28.i47.6716] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 11/02/2022] [Accepted: 11/23/2022] [Indexed: 12/19/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19), caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has escalated into a global tragedy afflicting human health, life, and social governance. Through the increasing depth of research and a better understanding of this disease, it has been ascertained that, in addition to the lungs, SARS-CoV-2 can also induce injuries to other organs including the liver. Liver injury is a common clinical manifestation of COVID-19, particularly in severe cases, and is often associated with a poorer prognosis and higher severity of COVID-19. This review focuses on the general existing information on liver injury caused by COVID-19, including risk factors and subpopulations of liver injury in COVID-19, the association between preexisting liver diseases and the severity of COVID-19, and the potential mechanisms by which SARS-CoV-2 affects the liver. This review may provide some useful information for the development of therapeutic and preventive strategies for COVID-19-associated liver injury.
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Affiliation(s)
- Wen-Shu Hu
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Fang-Ying Jiang
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Wen Shu
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Rong Zhao
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Ji-Min Cao
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - De-Ping Wang
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
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Krishnan A, Prichett L, Liu Y, Ting PS, Alqahtani SA, Kim AK, Ma M, Hamilton JP, Woreta TA, Chen PH. Risk of Severe Illness and Risk Factors of Outcomes of COVID-19 in Hospitalized Patients with Chronic Liver Disease in a Major U. S. Hospital Network. Can J Gastroenterol Hepatol 2022; 2022:8407990. [PMID: 36387036 PMCID: PMC9649328 DOI: 10.1155/2022/8407990] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 10/01/2022] [Accepted: 10/12/2022] [Indexed: 11/06/2022] Open
Abstract
METHODS We studied 2731 patients with known CLD who were hospitalized at the Johns Hopkins Health System with COVID-19 between March 1, 2020, and December 15, 2021. The primary outcome was all-cause mortality, and secondary outcomes were MV and vasopressors. Multivariable Cox regression models were performed to explore factors associated with the outcomes. RESULTS Overall, 80.1% had severe COVID-19, all-cause mortality was 8.9%, 12.8% required MV, and 11.2% received vasopressor support. Older patients with underlying comorbidities were more likely to have severe COVID-19. There was association between elevated aminotransferases and total bilirubin with more severe COVID-19. Hepatic decompensation was independently associated with all-cause mortality (HR 2.94; 95% CI 1.23-7.06). Alcohol-related liver disease (ALD, HR 2.79, 95% CI, 1.00-8.02) was independently associated with increased risk for MV, and independent factors related to vasopressor support were chronic pulmonary disease and underlying malignancy. CONCLUSIONS COVID-19 infection in patients with CLD is associated with poor outcomes. SARS-CoV-2 infection in patients with hepatic decompensation was associated with an increased risk of in-hospital mortality hazard, and ALD among patients with COVID-19 was associated with an increased hazard for MV.
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Affiliation(s)
- Arunkumar Krishnan
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Laura Prichett
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Yisi Liu
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Peng-sheng Ting
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Saleh A. Alqahtani
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- Liver Transplant Center, King Faisal Specialist Hospital and Research Center, Riyadh 12713, Saudi Arabia
| | - Amy K. Kim
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Michelle Ma
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - James P. Hamilton
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Tinsay A. Woreta
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Po-Hung Chen
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
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Elhence A, Vaishnav M, Biswas S, Anand A, Gunjan D, Kedia S, Mahapatra SJ, Nayak B, Sheikh S, Soni KD, Trikha A, Goel A, Shalimar. Predictors of in-hospital Outcomes in Patients With Cirrhosis and Coronavirus Disease-2019. J Clin Exp Hepatol 2022; 12:876-886. [PMID: 34728983 PMCID: PMC8553413 DOI: 10.1016/j.jceh.2021.10.014] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 10/14/2021] [Indexed: 02/06/2023] Open
Abstract
Background Coronavirus disease-2019 (COVID-19) cases continue to increase globally. Poor outcomes in patients with COVID-19 and cirrhosis have been reported; predictors of outcome are unclear. The existing data is from the early part of the pandemic when variants of concern (VOC) were not reported. Aims We aimed to assess the outcomes and predictors in patients with cirrhosis and COVID-19. We also compared the differences in outcomes between the first wave of pandemic and the second wave. Methods In this retrospective analysis of a prospectively maintained database, data on consecutive cirrhosis patients (n = 221) admitted to the COVID-19 care facility of a tertiary care center in India were evaluated for presentation, the severity of liver disease, the severity of COVID-19, and outcomes. Results The clinical presentation included: 18 (8.1%) patients had compensated cirrhosis, 139 (62.9%) acute decompensation (AD), and 64 (29.0%) had an acute-on-chronic liver failure (ACLF). Patients with ACLF had more severe COVID-19 infection than those with compensated cirrhosis and AD (54.7% vs. 16.5% and 33.3%, P < 0.001). The overall mortality was 90 (40.7%), the highest among ACLF (72.0%). On multivariate analysis, independent predictors of mortality were high leukocyte count, alkaline phosphatase, creatinine, child class, model for end-stage liver disease (MELD) score, and COVID-19 severity. The second wave had more cases of severe COVID-19 as compared to the first wave, with a similar MELD score and Child score. The overall mortality was similar between the two waves. Conclusion Patients with COVID-19 and cirrhosis have high mortality (40%), particularly those with ACLF (72%). A higher leukocyte count, creatinine, alkaline phosphatase, Child class, and MELD score are predictors of mortality.
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Key Words
- ACLF, acute-on-chronic liver failure
- AD, acute decompensation
- AIH, autoimmune hepatitis
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- Alk P, alkaline phosphatase
- COVID-19, Coronavirus disease-2019
- CTP, Child-Turcotte-Pugh
- EHPVO, extrahepatic portal vein obstruction
- HBV
- HBV, hepatitis B virus
- HCV
- HCV, hepatitis C virus
- INR, international normalized ratio
- MELD, model for end-stage liver disease
- MODS, multiorgan dysfunction syndrome
- NAAT, Nucleic Acid Amplification Test
- NAFLD
- NAFLD, nonalcoholic fatty liver disease
- NCPF, noncirrhotic portal fibrosis
- TLC, Total leukocyte count
- VOC, variants of concern
- VOI, variants of interest
- alcohol
- portal hypertension
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Affiliation(s)
- Anshuman Elhence
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Manas Vaishnav
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Sagnik Biswas
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Abhinav Anand
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Deepak Gunjan
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Soumya J. Mahapatra
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Baibaswata Nayak
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Sabreena Sheikh
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Kapil D. Soni
- Department of Anaesthesiology, Pain Medicine and Critical Care. All India Institute of Medical Sciences, New Delhi, India
| | - Anjan Trikha
- Department of Anaesthesiology, Pain Medicine and Critical Care. All India Institute of Medical Sciences, New Delhi, India
| | - Amit Goel
- Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
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Brozat JF, Hanses F, Haelberger M, Stecher M, Dreher M, Tometten L, Ruethrich MM, Vehreschild JJ, Trautwein C, Borgmann S, Vehreschild MJGT, Jakob CEM, Stallmach A, Wille K, Hellwig K, Isberner N, Reuken PA, Geisler F, Nattermann J, Bruns T. COVID-19 mortality in cirrhosis is determined by cirrhosis-associated comorbidities and extrahepatic organ failure: Results from the multinational LEOSS registry. United European Gastroenterol J 2022; 10:409-424. [PMID: 35482663 PMCID: PMC9103364 DOI: 10.1002/ueg2.12232] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 04/11/2022] [Indexed: 02/06/2023] Open
Abstract
Background and Objective International registries have reported high mortality rates in patients with liver disease and COVID‐19. However, the extent to which comorbidities contribute to excess COVID‐19 mortality in cirrhosis is controversial. Methods We used the multinational Lean European Open Survey on SARS‐CoV‐2‐infected patients (LEOSS) to identify patients with cirrhosis documented between March 2020 and March 2021, when the wild‐type and alpha variant were predominant. We compared symptoms, disease progression and mortality after propensity score matching (PSM) for age, sex, obesity, smoking status, and concomitant diseases. Mortality was also compared with that of patients with spontaneous bacterial peritonitis (SBP) without SARS‐CoV‐2 infection, a common bacterial infection and well‐described precipitator of acute‐on‐chronic liver failure. Results Among 7096 patients with SARS‐CoV‐2 infection eligible for analysis, 70 (0.99%) had cirrhosis, and all were hospitalized. Risk factors for severe COVID‐19, such as diabetes, renal disease, and cardiovascular disease were more frequent in patients with cirrhosis. Case fatality rate in patients with cirrhosis was 31.4% with the highest odds of death in patients older than 65 years (43.6% mortality; odds ratio [OR] 4.02; p = 0.018), Child‐Pugh class C (57.1%; OR 4.00; p = 0.026), and failure of two or more organs (81.8%; OR 19.93; p = 0.001). After PSM for demographics and comorbidity, the COVID‐19 case fatality of patients with cirrhosis did not significantly differ from that of matched patients without cirrhosis (28.8% vs. 26.1%; p = 0.644) and was similar to the 28‐day mortality in a comparison group of patients with cirrhosis and SBP (33.3% vs. 31.5%; p = 1.000). Conclusions In immunologically naïve patients with cirrhosis, mortality from wild‐type SARS‐CoV‐2 and the alpha variant is high and is largely determined by cirrhosis‐associated comorbidities and extrahepatic organ failure.
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Affiliation(s)
- Jonathan F Brozat
- Department of Internal Medicine III, University Hospital RWTH Aachen, RWTH Aachen University, Aachen, Germany
| | - Frank Hanses
- Emergency Department, University Hospital Regensburg, Regensburg, Germany.,Department for Infectious Diseases and Infection Control, University Hospital, Regensburg, Germany
| | | | - Melanie Stecher
- Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.,German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany
| | - Michael Dreher
- Department of Pneumology and Intensive Care Medicine, Internal Medicine V, University Hospital RWTH Aachen, RWTH Aachen University, Aachen, Germany
| | - Lukas Tometten
- Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.,Clinic for Intensive Care and Emergency Medicine, Hospital Ernst von Bergmann, Potsdam, Germany
| | - Maria M Ruethrich
- Department of Internal Medicine II, Hematology and Medical Oncology, University Hospital Jena, Jena, Germany
| | - Janne J Vehreschild
- Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.,German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.,Department II of Internal Medicine, Hematology/Oncology, Goethe University, Frankfurt, Frankfurt Am Main, Germany
| | - Christian Trautwein
- Department of Internal Medicine III, University Hospital RWTH Aachen, RWTH Aachen University, Aachen, Germany
| | - Stefan Borgmann
- Department of Infectious Diseases and Infection Control, Ingolstadt Hospital, Ingolstadt, Germany
| | - Maria J G T Vehreschild
- Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany
| | - Carolin E M Jakob
- Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.,German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany
| | - Andreas Stallmach
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
| | - Kai Wille
- Johannes Wesling Klinikum Minden, Oncology, Haemostaseology and Palliative Care, Johannes Wesling Klinikum, University of Bochum, Minden, Germany
| | - Kerstin Hellwig
- Department of Neurology, St. Josef-Hospital Bochum, Ruhr University Bochum, Bochum, Germany
| | - Nora Isberner
- Department of Internal Medicine II, Infectious Diseases, University Hospital Wuerzburg, Wuerzburg, Germany
| | - Philipp A Reuken
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
| | - Fabian Geisler
- Department of Internal Medicine II, School of Medicine, Technical University of Munich, University Hospital Rechts der Isar, Munich, Germany
| | - Jacob Nattermann
- Department of Internal Medicine I, UKB University Hospital Bonn, Bonn, Germany
| | - Tony Bruns
- Department of Internal Medicine III, University Hospital RWTH Aachen, RWTH Aachen University, Aachen, Germany
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