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Yendewa GA, Olasehinde T, Mulindwa F, Salata RA, Mohareb AM, Jacobson JM. Chronic Hepatitis B and COVID-19 Clinical Outcomes in the United States: A Multisite Retrospective Cohort Study. Open Forum Infect Dis 2025; 12:ofaf013. [PMID: 39896985 PMCID: PMC11786054 DOI: 10.1093/ofid/ofaf013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Accepted: 01/08/2025] [Indexed: 02/04/2025] Open
Abstract
Background There is conflicting evidence regarding the impact of chronic hepatitis B virus (HBV) on SARS-CoV-2 outcomes. Additionally, the impact of SARS-CoV-2 vaccination and variant periods on outcomes in HBV/SARS-CoV-2 coinfection remain unexplored. Methods We utilized the TriNetX database to compare adults with HBV/SARS-CoV-2 (vs SARS-CoV-2 alone) across 97 US healthcare systems from 2020 to 2023. We assessed the odds of all inpatient hospitalizations, intensive care unit admissions, mechanical ventilation, 30-day, 90-day, and overall mortality. In sensitivity analyses, we excluded HIV, hepatitis C virus, and transplant cases and stratified the HBV/SARS-CoV-2 cohort by cirrhosis status. We applied propensity score matching to address confounding and reported odds ratios (OR) with 95% confidence intervals (CI). Results Of 4 206 774 individuals with SARS-CoV-2, about 0.2% (8293) were HBV/SARS-CoV-2. Individuals with HBV/SARS-CoV-2 (vs SARS-CoV-2 alone) had higher odds of intensive care unit admissions (OR, 1.18; 95% CI, 1.02-1.36), 90-day (OR, 1.22; 95% CI, 1.01-1.41) and overall mortality (OR, 1.18; 95% CI, 1.06-1.33). In sensitivity analyses, those with HBV/SARS-CoV-2 and cirrhosis had a 2.0- to 2.50-fold higher odds of adverse outcomes. Notably, even individuals with HBV/SARS-CoV-2 without cirrhosis had higher odds of mortality. Vaccinated (vs unvaccinated) individuals with HBV/SARS-CoV-2 had 57%, 54%, and 29% reduction in 30-day, 90-day, and overall mortality, respectively. The pre-Delta variant period was associated with higher odds of hospitalization compared to the Omicron but not the Delta period. Conclusions Chronic HBV was associated with worse SARS-CoV-2 outcomes, whereas SARS-CoV-2 vaccination reduced the likelihood of adverse outcomes.
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Affiliation(s)
- George A Yendewa
- Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
- Division of Infectious Diseases and HIV Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Temitope Olasehinde
- Division of Infectious Diseases and HIV Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Frank Mulindwa
- Department of Medicine, United Health Services Wilson Medical Center, Johnson City, New York, USA
| | - Robert A Salata
- Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
- Division of Infectious Diseases and HIV Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Amir M Mohareb
- Center for Global Health, Massachusetts General Hospital, Boston, Massachusetts, USA
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - Jeffrey M Jacobson
- Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
- Division of Infectious Diseases and HIV Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
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Quek JWE, Loo JH, Lim EQ, Chung AHL, Othman ABB, Tan JJR, Barnett S, Nguyen MH, Wong YJ. Global epidemiology, natural history, maternal-to-child transmission, and treatment with DAA of pregnant women with HCV: a systematic review and meta-analysis. EClinicalMedicine 2024; 74:102727. [PMID: 39109190 PMCID: PMC11301193 DOI: 10.1016/j.eclinm.2024.102727] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Revised: 06/19/2024] [Accepted: 06/25/2024] [Indexed: 01/03/2025] Open
Abstract
BACKGROUND Pregnant women with hepatitis C virus (HCV) infection represent a special population in which treatment access remains limited despite its increasing prevalence. A reliable estimate of the burden and clinical outcomes of pregnant women with HCV infection is crucial for HCV elimination. We aimed to determine the prevalence, maternal-to-child transmission (MTCT), maternal and fetal complication rates, and direct acting antivirals (DAA) treatment outcomes of chronic HCV infection in pregnant women. METHODS We searched PubMed, EMBASE, Scopus, Web of Science from inception until March 1, 2024, for studies reporting on the prevalence, MTCT, complications of HCV infection, and treatment outcomes of DAA in pregnant women. Study quality was assessed using the Newcastle-Ottawa Scale. We performed subgroup analysis based on 9 variables to explore the source of heterogeneity in HCV prevalence. The PROSPERO registration number is CRD42024500023. FINDINGS From a total of 311,905,738 pregnant women from 333 studies, the pooled global seroprevalence of HCV in pregnant women was 2.6% (95% CI: 2.0-3.2, I 2 = 100%) which increased in patients with intravenous drug use and HIV. Majority of the HCV cases in pregnant women (75%) are diagnosed through universal screening. The pooled MTCT rate was 9.0% (95% CI: 6.6-11.7, I 2 = 79%), which was higher with HIV co-infection (OR: 3.1, 95% CI: 2.1-4.6, I 2 = 10%), but was not influenced by the mode of delivery or breastfeeding. Pregnant women with HCV infection had more maternal complications, including intrahepatic cholestasis, preterm delivery, and antepartum hemorrhage. Neonates of mothers with HCV had higher odds of being small for gestational age. The pooled rate of sustained virologic response (SVR12) among the 74 women treated with DAA during pregnancy was 98.4%, with no serious adverse events reported. INTERPRETATION HCV prevalence in pregnant women varies by geographic region and patient population, while MTCT occurs in almost one in ten viremic mothers. The incidence of both maternal and neonatal complications is significantly higher in patients with HCV infection. Limited data suggest that DAA are safe in pregnant women with HCV infection. FUNDING None.
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Affiliation(s)
- Joo Wei Ethan Quek
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jing Hong Loo
- Department of Gastroenterology & Hepatology, Changi General Hospital, Singapore
| | | | | | | | - Jarell Jie-Rae Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Scott Barnett
- Division of Gastroenterology & Hepatology, Stanford University Medical Centre, Palo Alto, CA, USA
| | - Mindie H. Nguyen
- Division of Gastroenterology & Hepatology, Stanford University Medical Centre, Palo Alto, CA, USA
- Department of Epidemiology and Population Health, Stanford University Medical Centre, Palo Alto, CA, USA
| | - Yu Jun Wong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Gastroenterology & Hepatology, Changi General Hospital, Singapore
- Duke-NUS Medical School, Singapore
- Division of Gastroenterology & Hepatology, University of Alberta, Edmonton, Canada
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Washirasaksiri C, Sayabovorn N, Ariyakunaphan P, Kositamongkol C, Chaisathaphol T, Sitasuwan T, Tinmanee R, Auesomwang C, Nimitpunya P, Woradetsittichai D, Chayakulkeeree M, Phoompoung P, Mayurasakorn K, Sookrung N, Tungtrongchitr A, Wanitphakdeedecha R, Muangman S, Senawong S, Tangjittipokin W, Sanpawitayakul G, Nopmaneejumruslers C, Vamvanij V, Phisalprapa P, Srivanichakorn W. Long-term multiple metabolic abnormalities among healthy and high-risk people following nonsevere COVID-19. Sci Rep 2023; 13:14336. [PMID: 37653091 PMCID: PMC10471587 DOI: 10.1038/s41598-023-41523-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 08/28/2023] [Indexed: 09/02/2023] Open
Abstract
Few studies have identified the metabolic consequences of the post-acute phase of nonsevere COVID-19. This prospective study examined metabolic outcomes and associated factors in nonsevere, RT-PCR-confirmed COVID-19. The participants' metabolic parameters, the prevalence of long-term multiple metabolic abnormalities (≥ 2 components), and factors influencing the prevalence were assessed at 1, 3, and 6 months post-onset. Six hundred individuals (mean age 45.5 ± 14.5 years, 61.7% female, 38% high-risk individuals) with nonsevere COVID-19 attended at least one follow-up visit. The prevalence of worsening metabolic abnormalities was 26.0% for BMI, 43.2% for glucose, 40.5% for LDL-c, 19.1% for liver, and 14.8% for C-reactive protein. Except for lipids, metabolic-component abnormalities were more prevalent in high-risk hosts than in healthy individuals. The prevalence of multiple metabolic abnormalities at the 6-month follow-up was 41.3% and significantly higher in high-risk than healthy hosts (49.2% vs 36.5%; P = 0.007). Factors independently associated with a lower risk of these abnormalities were being female, having dyslipidemia, and receiving at least 3 doses of the COVID-19 vaccine. These findings suggest that multiple metabolic abnormalities are the long-term consequences of COVID-19. For both high-risk and healthy individuals with nonsevere COVID-19, healthcare providers should monitor metabolic profiles, encourage healthy behaviors, and ensure complete vaccination.
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Affiliation(s)
- Chaiwat Washirasaksiri
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Bangkok Noi, Bangkok, 10700, Thailand
| | - Naruemit Sayabovorn
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Bangkok Noi, Bangkok, 10700, Thailand
| | - Pinyapat Ariyakunaphan
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Bangkok Noi, Bangkok, 10700, Thailand
| | - Chayanis Kositamongkol
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Bangkok Noi, Bangkok, 10700, Thailand
| | - Thanet Chaisathaphol
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Bangkok Noi, Bangkok, 10700, Thailand
| | - Tullaya Sitasuwan
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Bangkok Noi, Bangkok, 10700, Thailand
| | - Rungsima Tinmanee
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Bangkok Noi, Bangkok, 10700, Thailand
| | - Chonticha Auesomwang
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Bangkok Noi, Bangkok, 10700, Thailand
| | - Pongpol Nimitpunya
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Bangkok Noi, Bangkok, 10700, Thailand
| | - Diana Woradetsittichai
- Department of Nursing, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Methee Chayakulkeeree
- Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Pakpoom Phoompoung
- Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Korapat Mayurasakorn
- Siriraj Population Health and Nutrition Research Group, Department of Research Group and Research Network, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Nitat Sookrung
- Center of Research Excellence On Therapeutic Proteins and Antibody Engineering, Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Anchalee Tungtrongchitr
- Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | | | - Saipin Muangman
- Department of Anesthesiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Sansnee Senawong
- Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Watip Tangjittipokin
- Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Gornmigar Sanpawitayakul
- Division of Ambulatory Paediatrics, Department of Paediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Cherdchai Nopmaneejumruslers
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Bangkok Noi, Bangkok, 10700, Thailand
| | - Visit Vamvanij
- Department of Orthopaedic Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Pochamana Phisalprapa
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Bangkok Noi, Bangkok, 10700, Thailand
| | - Weerachai Srivanichakorn
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Bangkok Noi, Bangkok, 10700, Thailand.
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Schlesinger S, Lang A, Christodoulou N, Linnerz P, Pafili K, Kuss O, Herder C, Neuenschwander M, Barbaresko J, Roden M. Risk phenotypes of diabetes and association with COVID-19 severity and death: an update of a living systematic review and meta-analysis. Diabetologia 2023; 66:1395-1412. [PMID: 37204441 PMCID: PMC10198038 DOI: 10.1007/s00125-023-05928-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 03/16/2023] [Indexed: 05/20/2023]
Abstract
AIMS/HYPOTHESIS To provide a systematic overview of the current body of evidence on high-risk phenotypes of diabetes associated with COVID-19 severity and death. METHODS This is the first update of our recently published living systematic review and meta-analysis. Observational studies investigating phenotypes in individuals with diabetes and confirmed SARS-CoV-2 infection with regard to COVID-19-related death and severity were included. The literature search was conducted from inception up to 14 February 2022 in PubMed, Epistemonikos, Web of Science and the COVID-19 Research Database and updated using PubMed alert to 1 December 2022. A random-effects meta-analysis was used to calculate summary relative risks (SRRs) with 95% CIs. The risk of bias was evaluated using the Quality in Prognosis Studies (QUIPS) tool and the certainty of evidence using the GRADE approach. RESULTS A total of 169 articles (147 new studies) based on approximately 900,000 individuals were included. We conducted 177 meta-analyses (83 on COVID-19-related death and 94 on COVID-19 severity). Certainty of evidence was strengthened for associations between male sex, older age, blood glucose level at admission, chronic insulin use, chronic metformin use (inversely) and pre-existing comorbidities (CVD, chronic kidney disease, chronic obstructive pulmonary disease) and COVID-19-related death. New evidence with moderate to high certainty emerged for the association between obesity (SRR [95% CI] 1.18 [1.04, 1.34], n=21 studies), HbA1c (53-75 mmol/mol [7-9%]: 1.18 [1.06, 1.32], n=8), chronic glucagon-like peptide-1 receptor agonist use (0.83 [0.71, 0.97], n=9), pre-existing heart failure (1.33 [1.21, 1.47], n=14), pre-existing liver disease (1.40 [1.17, 1.67], n=6), the Charlson index (per 1 unit increase: 1.33 [1.13, 1.57], n=2), high levels of C-reactive protein (per 5 mg/l increase: 1.07 [1.02, 1.12], n=10), aspartate aminotransferase level (per 5 U/l increase: 1.28 [1.06, 1.54], n=5), eGFR (per 10 ml/min per 1.73 m2 increase: 0.80 [0.71, 0.90], n=6), lactate dehydrogenase level (per 10 U/l increase: 1.03 [1.01, 1.04], n=7) and lymphocyte count (per 1×109/l increase: 0.59 [0.40, 0.86], n=6) and COVID-19-related death. Similar associations were observed between risk phenotypes of diabetes and severity of COVID-19, with some new evidence on existing COVID-19 vaccination status (0.32 [0.26, 0.38], n=3), pre-existing hypertension (1.23 [1.14, 1.33], n=49), neuropathy and cancer, and high IL-6 levels. A limitation of this study is that the included studies are observational in nature and residual or unmeasured confounding cannot be ruled out. CONCLUSIONS/INTERPRETATION Individuals with a more severe course of diabetes and pre-existing comorbidities had a poorer prognosis of COVID-19 than individuals with a milder course of the disease. REGISTRATION PROSPERO registration no. CRD42020193692. PREVIOUS VERSION This is a living systematic review and meta-analysis. The previous version can be found at https://link.springer.com/article/10.1007/s00125-021-05458-8 FUNDING: The German Diabetes Center (DDZ) is funded by the German Federal Ministry of Health and the Ministry of Culture and Science of the State North Rhine-Westphalia. This study was supported in part by a grant from the German Federal Ministry of Education and Research to the German Center for Diabetes Research (DZD).
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Affiliation(s)
- Sabrina Schlesinger
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
- German Center for Diabetes Research (DZD), Partner Düsseldorf, München-Neuherberg, Germany.
| | - Alexander Lang
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Nikoletta Christodoulou
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Philipp Linnerz
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Kalliopi Pafili
- German Center for Diabetes Research (DZD), Partner Düsseldorf, München-Neuherberg, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Oliver Kuss
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), Partner Düsseldorf, München-Neuherberg, Germany
- Centre for Health and Society, Faculty of Medicine, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Christian Herder
- German Center for Diabetes Research (DZD), Partner Düsseldorf, München-Neuherberg, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Manuela Neuenschwander
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), Partner Düsseldorf, München-Neuherberg, Germany
| | - Janett Barbaresko
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Michael Roden
- German Center for Diabetes Research (DZD), Partner Düsseldorf, München-Neuherberg, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
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Zyoud SH. Research landscape on COVID-19 and liver dysfunction: A bibliometric analysis. World J Gastroenterol 2023; 29:4356-4367. [PMID: 37545639 PMCID: PMC10401660 DOI: 10.3748/wjg.v29.i27.4356] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 06/16/2023] [Accepted: 06/27/2023] [Indexed: 07/13/2023] Open
Abstract
BACKGROUND The global spread of severe acute respiratory syndrome coronavirus 2, responsible for coronavirus disease 2019 (COVID-19), poses a significant risk to public health. Beyond the respiratory issues initially associated with the condition, severe cases of COVID-19 can also lead to complications in other organs, including the liver. Patients with severe COVID-19 may exhibit various clinical signs of liver dysfunction, ranging from minor elevations in liver enzymes without symptoms to more serious cases of impaired liver function. Liver damage is more commonly observed in patients with severe or critical forms of the disease. AIM To present the research landscape on COVID-19 and liver dysfunction while also offering valuable insights into the prominent areas of interest within this particular domain. METHODS On 18 February 2023, Scopus was utilised to conduct a comprehensive exploration of the relationship between COVID-19 and the liver dysfunction. The investigation encompassed the period from 1 January 2020 to 31 December 2022. Primary sources were meticulously examined and organised in a Microsoft Excel 2013 spreadsheet, categorised by journal, institution, funding agency, country and citation type. VOSviewer version 1.6.18 was employed to explore the prominent topics and knowledge network related to the subject. RESULTS There were 2336 publications on COVID-19 and liver dysfunction analysed in this study, of which 558 were published in 2020, 891 in 2021 and 887 in 2022. Researchers from 111 different countries participated in the retrieved documents. The United States contributed the most studies, with 497 documents, representing 21.28% of the total, followed by China with 393 documents (16.82%) and Italy with 255 documents (10.92%). In the context of research related to COVID-19 and the liver, co-occurrence analysis identified three distinct clusters of topics: (1) 'COVID-19 vaccines in liver transplant recipients'; (2) 'liver function tests as a predictor of the severity and clinical outcomes in hospitalised patients'; and (3) 'care of patients with liver disease during the COVID-19 pandemic'. CONCLUSION This bibliometric study provides a comprehensive overview of liver-related publications in COVID-19 research over the past 3 years. This study highlights the significant contributions of high-income nations, particularly the United States, China, and Italy, to the production of liver-related scholarly literature in this field. Most of the articles focused on liver dysfunction in patients with COVID-19 and the implications of the virus for gastroenterologists and hepatologists.
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Affiliation(s)
- Sa'ed H Zyoud
- Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine
- Poison Control and Drug Information Center (PCDIC), College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine
- Clinical Research Centre, An-Najah National University Hospital, Nablus 44839, Palestine
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Mangoni AA, Zinellu A. An Updated Systematic Review and Meta-Analysis of the Association between the De Ritis Ratio and Disease Severity and Mortality in Patients with COVID-19. Life (Basel) 2023; 13:1324. [PMID: 37374107 DOI: 10.3390/life13061324] [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: 05/16/2023] [Accepted: 06/01/2023] [Indexed: 06/29/2023] Open
Abstract
Patients with Coronavirus disease 2019 (COVID-19) often have elevations in markers of liver injury, particularly serum aspartate transaminase (AST) and alanine transaminase (ALT). Such alterations may affect the AST/ALT ratio (De Ritis ratio) and, potentially, clinical outcomes. We conducted an updated systematic review and meta-analysis of the association between the De Ritis ratio and COVID-19 severity and mortality in hospitalized patients. PubMed, Web of Science, and Scopus were searched between 1 December 2019 and 15 February 2023. The Joanna Briggs Institute Critical Appraisal Checklist and the Grading of Recommendations, Assessment, Development, and Evaluation were used to assess the risk of bias and the certainty of the evidence, respectively. Twenty-four studies were identified. The De Ritis ratio on admission was significantly higher in patients with severe disease and non-survivors vs. patients with non-severe disease and survivors (15 studies, weighted mean difference = 0.36, 95% CI 0.24 to 0.49, p < 0.001). The De Ritis ratio was also associated with severe disease and/or mortality using odds ratios (1.83, 95% CI 1.40 to 2.39, p ˂ 0.001; nine studies). Similar results were observed using hazard ratios (2.36, 95% CI 1.17 to 4.79, p = 0.017; five studies). In six studies, the pooled area under the receiver operating characteristic curve was 0.677 (95% CI 0.612 to 0.743). In our systematic review and meta-analysis, higher De Ritis ratios were significantly associated with severe disease and mortality in COVID-19 patients. Therefore, the De Ritis ratio can be useful for early risk stratification and management in this patient group (PROSPERO registration number: CRD42023406916).
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Affiliation(s)
- Arduino A Mangoni
- Discipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Bedford Park, SA 5042, Australia
- Department of Clinical Pharmacology, Flinders Medical Centre, Southern Adelaide Local Health Network, Bedford Park, SA 5042, Australia
| | - Angelo Zinellu
- Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy
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Grinevich VB, Lazebnik LB, Kravchuk YA, Radchenko VG, Tkachenko EI, Pershko AM, Seliverstov PV, Salikova CP, Zhdanov KV, Kozlov KV, Makienko VV, Potapova IV, Ivanyuk ES, Egorov DV, Sas EI, Korzheva MD, Kozlova NM, Ratnikova AK, Ratnikov VA, Sitkin SI, Bolieva LZ, Turkina CV, Abdulganieva DI, Ermolova TV, Kozhevnikova SA, Tarasova LV, Myazin RG, Khomeriki NM, Pilat TL, Kuzmina LP, Khanferyan RA, Novikova VP, Polunina AV, Khavkin AI. Gastrointestinal disorders in post-COVID syndrome. Clinical guidelines. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2023:4-68. [DOI: 10.31146/1682-8658-ecg-208-12-4-68] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/26/2023]
Abstract
Summary Post- COVID syndrome refers to the long-term consequences of a new coronavirus infection COVID-19, which includes a set of symptoms that develop or persist after COVID-19. Symptoms of gastrointestinal disorders in post- COVID syndrome, due to chronic infl ammation, the consequences of organ damage, prolonged hospitalization, social isolation, and other causes, can be persistent and require a multidisciplinary approach. The presented clinical practice guidelines consider the main preventive and therapeutic and diagnostic approaches to the management of patients with gastroenterological manifestations of postCOVID syndrome. The Guidelines were approved by the 17th National Congress of Internal Medicine and the 25th Congress of Gastroenterological Scientifi c Society of Russia.
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Affiliation(s)
| | - L. B. Lazebnik
- A. I. Yevdokimov Moscow State University of Medicine and Dentistry
| | | | | | | | | | | | | | | | - K. V. Kozlov
- Military Medical Academy named after S. M. Kirov
| | | | | | | | - D. V. Egorov
- Military Medical Academy named after S. M. Kirov
| | - E. I. Sas
- Military Medical Academy named after S. M. Kirov
| | | | | | - A. K. Ratnikova
- North-West District Scientifi c and Clinical Center named after L. G. Sokolov Federal Medical and Biological Agency
| | - V. A. Ratnikov
- North-West District Scientifi c and Clinical Center named after L. G. Sokolov Federal Medical and Biological Agency
| | - S. I. Sitkin
- North-Western state medical University named after I. I. Mechnikov;
Almazov National Medical Research Centre
| | | | | | | | - T. V. Ermolova
- North-Western state medical University named after I. I. Mechnikov
| | | | | | | | - N. M. Khomeriki
- Moscow Regional Research Clinical Institute n. a. M. F. Vladimirsky”
| | - T. L. Pilat
- Scientifi c Research Institute of labour medicine named after academician N. F. Izmerov
| | - L. P. Kuzmina
- Scientifi c Research Institute of labour medicine named after academician N. F. Izmerov;
I. M. Sechenov First Moscow State Medical University (Sechenov University)
| | | | | | | | - A. I. Khavkin
- Russian National Research Medical University named after N. I. Pirogov
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Khullar N, Bhatti JS, Singh S, Thukral B, Reddy PH, Bhatti GK. Insight into the liver dysfunction in COVID-19 patients: Molecular mechanisms and possible therapeutic strategies. World J Gastroenterol 2023; 29:2064-2077. [PMID: 37122601 PMCID: PMC10130970 DOI: 10.3748/wjg.v29.i14.2064] [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: 09/28/2022] [Revised: 10/23/2022] [Accepted: 03/21/2023] [Indexed: 04/13/2023] Open
Abstract
As of June 2022, more than 530 million people worldwide have become ill with coronavirus disease 2019 (COVID-19). Although COVID-19 is most commonly associated with respiratory distress (severe acute respiratory syndrome), meta-analysis have indicated that liver dysfunction also occurs in patients with severe symptoms. Current studies revealed distinctive patterning in the receptors on the hepatic cells that helps in viral invasion through the expression of angiotensin-converting enzyme receptors. It has also been reported that in some patients with COVID-19, therapeutic strategies, including repurposed drugs (mitifovir, lopinavir/ritonavir, tocilizumab, etc.) triggered liver injury and cholestatic toxicity. Several proven indicators support cytokine storm-induced hepatic damage. Because there are 1.5 billion patients with chronic liver disease worldwide, it becomes imperative to critically evaluate the molecular mechanisms concerning hepatotropism of COVID-19 and identify new potential therapeutics. This review also designated a comprehensive outlook of comorbidities and the impact of lifestyle and genetics in managing patients with COVID-19.
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Affiliation(s)
- Naina Khullar
- Department of Zoology, Mata Gujri College, Fatehgarh Sahib 140407, Punjab, India
| | - Jasvinder Singh Bhatti
- Laboratory of Translational Medicine and Nanotherapeutics, Department of Human Genetics and Molecular Medicine, School of Health Sciences, Central University of Punjab, Bathinda 151401, Punjab, India
| | - Satwinder Singh
- Department of Computer Science and Technology, Central University of Punjab, Bathinda 151401, Punjab, India
| | - Bhawana Thukral
- Department of Nutrition and Dietetics, University Institute of Applied Health Sciences, Chandigarh University, Mohali 140413, Punjab, India
| | - P Hemachandra Reddy
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, United States
| | - Gurjit Kaur Bhatti
- Department of Medical Lab Technology, University Institute of Applied Health Sciences, Chandigarh University, Mohali 140413, Punjab, India
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9
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Sanyaolu A, Marinkovic A, Abbasi AF, Prakash S, Patidar R, Desai P, Williams M, Jan A, Hamdy K, Solomon R, Balendra V, Ansari M, Shazley O, Khan N, Annan R, Dixon Y, Okorie C, Antonio A. Effect of SARS-CoV-2 infection on the liver. World J Virol 2023; 12:109-121. [PMID: 37033147 PMCID: PMC10075054 DOI: 10.5501/wjv.v12.i2.109] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Revised: 01/04/2023] [Accepted: 02/01/2023] [Indexed: 03/21/2023] Open
Abstract
There have been numerous concerns about the disease and how it affects the human body since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic began in December 2019. The impact of SARS-CoV-2 on the liver is being carefully investigated due to an increase in individuals with hepatitis and other liver illnesses, such as alcoholic liver disease. Additionally, the liver is involved in the metabolism of numerous drugs used to treat comorbidities and coronavirus disease 2019 (COVID-19). Determining how SARS-CoV-2 affects the liver and what factors place individuals with COVID-19 at a higher risk of developing liver problems are the two main objectives of this study. This evaluation of the literature included research from three major scientific databases. To provide an update on the current impact of COVID-19 on the liver, data was collected and relevant information was incorporated into the review. With more knowledge about the effect of the disease on the liver, better management and therapeutics can be developed, and education can ultimately save lives and reduce the long-term impact of the pandemic on our population.
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Affiliation(s)
- Adekunle Sanyaolu
- Department of Public Health, Federal Ministry of Health, Abuja, Nigeria, Abuja 0000, FCT, Nigeria
| | - Aleksandra Marinkovic
- Department of Basic Medical Science, Saint James School of Medicine, The Quarter 2640 0000, Anguilla
| | - Abu Fahad Abbasi
- Department of Internal Medicine, Loyola University Medical Center, Maywood, Illinois, IL 60153, United States
| | - Stephanie Prakash
- Department of Basic Medical Science, Saint James School of Medicine, The Quarter 2640 0000, Anguilla
| | - Risha Patidar
- Department of Basic Medical Science, Saint James School of Medicine, The Quarter 2640 0000, Anguilla
| | - Priyank Desai
- Department of Basic Medical Science, American University of Saint Vincent School of Medicine, Saint Vincent and the Grenadines 0000, Saint Vincent and the Grenadines
| | - Martina Williams
- Department of Basic Medical Science, Saint James School of Medicine, The Quarter 2640 0000, Anguilla
| | - Abdul Jan
- Department of Basic Medical Science, Windsor University School of Medicine, Cayon 0000, Saint Kitts and Nevis
| | - Kareem Hamdy
- Department of Basic Medical Science, Saint James School of Medicine, The Quarter 2640 0000, Anguilla
| | - Rachael Solomon
- Department of Basic Medical Science, Caribbean Medical University School of Medicine, Willemstad 0000, Curaçao, Netherlands Antilles
| | - Vyshnavy Balendra
- Department of Basic Medical Science, Saint James School of Medicine, The Quarter 2640 0000, Anguilla
| | - Maaz Ansari
- Department of Basic Medical Science, Saint James School of Medicine, The Quarter 2640 0000, Anguilla
| | - Omar Shazley
- Basic Medical Science, Saint James School of Medicine, Saint Vincent and the Grenadines 0000, Saint Vincent and the Grenadines
| | - Nasar Khan
- Department of Basic Medical Science, Windsor University School of Medicine, Cayon 0000, Saint Kitts and Nevis
| | - Rochelle Annan
- University of Health Sciences Antigua School of Medicine, Piccadilly, St. John's Antigua
| | - Yashika Dixon
- Department of Basic Medical Science, Windsor University School of Medicine, Cayon 0000, Saint Kitts and Nevis
| | - Chuku Okorie
- Department of Science, Union County College, Plainfield, New Jersey, NJ 07016, United States
| | - Afolabi Antonio
- Department of Internal Medicine, Lloydminster Regional Hospital, Lloydminster S9V 1Y5, Saskatchewan, Canada
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10
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Gildea DT, Woo SM, O’Connor CE, Rangnekar AS. COVID-19-Associated Liver Injury. Hepat Med 2023; 15:1-9. [PMID: 36852138 PMCID: PMC9960793 DOI: 10.2147/hmer.s384108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 02/11/2023] [Indexed: 03/01/2023] Open
Abstract
This review analyzes data regarding liver injury associated with COVID-19 infection. We discuss reported effects on the liver from both COVID-19 and COVID-19 treatment as well as pathophysiology, review the potential role of drug-induced liver injury as an etiology of COVID-19-associated liver injury, and touch on other reports of significant outcomes including COVID-19 cholangiopathy and autoimmune hepatitis. Finally, we review the implications of COVID-19 infection in liver transplant recipients.
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Affiliation(s)
- Daniel T Gildea
- Department of Internal Medicine, MedStar Georgetown University Hospital, Washington, DC, USA,Correspondence: Daniel T Gildea, Tel +1 302-985-7777, Email
| | - Stephanie M Woo
- Department of Gastroenterology, MedStar Georgetown University Hospital, Washington, DC, USA
| | | | - Amol S Rangnekar
- MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Washington, DC, USA
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11
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Cheung KS, Lam LK, Mao X, Tan JT, Ooi PH, Zhang R, Chan KH, Hung IFN, Seto WK, Yuen MF. Effect of Moderate to Severe Hepatic Steatosis on Vaccine Immunogenicity against Wild-Type and Mutant Virus and COVID-19 Infection among BNT162b2 Recipients. Vaccines (Basel) 2023; 11:497. [PMID: 36992081 PMCID: PMC10054100 DOI: 10.3390/vaccines11030497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/18/2023] [Accepted: 02/20/2023] [Indexed: 02/24/2023] Open
Abstract
BACKGROUND We aimed to investigate the effect of non-alcoholic fatty liver disease (NAFLD) on BNT162b2 immunogenicity against wild-type SARS-CoV-2 and variants and infection outcome, as data are lacking. METHODS Recipients of two doses of BNT162b2 were prospectively recruited. Outcomes of interest were seroconversion of neutralizing antibody by live virus microneutralization (vMN) to SARS-CoV-2 strains (wild-type, delta and omicron variants) at day 21, 56 and 180 after first dose. Exposure of interest was moderate-to-severe NAFLD (controlled attenuation parameter ≥ 268 dB/M on transient elastography). We calculated adjusted odds ratio (aOR) of infection with NAFLD by adjusting for age, sex, overweight/obesity, diabetes and antibiotic use. RESULTS Of 259 BNT162b2 recipients (90 (34.7%) male; median age: 50.8 years (IQR: 43.6-57.8)), 68 (26.3%) had NAFLD. For wild type, there was no difference in seroconversion rate between NAFLD and control groups at day 21 (72.1% vs. 77.0%; p = 0.42), day 56 (100% vs. 100%) and day 180 (100% and 97.2%; p = 0.22), respectively. For the delta variant, there was no difference also at day 21 (25.0% vs. 29.5%; p = 0.70), day 56 (100% vs. 98.4%; p = 0.57) and day 180 (89.5% vs. 93.3%; p = 0.58), respectively. For the omicron variant, none achieved seroconversion at day 21 and 180. At day 56, there was no difference in seroconversion rate (15.0% vs. 18.0%; p = 0.76). NAFLD was not an independent risk factor of infection (aOR: 1.50; 95% CI: 0.68-3.24). CONCLUSIONS NAFLD patients receiving two doses of BNT162b2 had good immunogenicity to wild-type SARS-CoV-2 and the delta variant but not the omicron variant, and they were not at higher risk of infection compared with controls.
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Affiliation(s)
- Ka Shing Cheung
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
- Department of Medicine, The University of Hong Kong, Shenzhen Hospital, Shenzhen 518009, China
| | - Lok Ka Lam
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Xianhua Mao
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Jing Tong Tan
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Poh Hwa Ooi
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Ruiqi Zhang
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Kwok Hung Chan
- Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Ivan F. N. Hung
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Wai Kay Seto
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
- Department of Medicine, The University of Hong Kong, Shenzhen Hospital, Shenzhen 518009, China
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong
| | - Man Fung Yuen
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong
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12
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Lempesis IG, Karlafti E, Papalexis P, Fotakopoulos G, Tarantinos K, Lekakis V, Papadakos SP, Cholongitas E, Georgakopoulou VE. COVID-19 and liver injury in individuals with obesity. World J Gastroenterol 2023; 29:908-916. [PMID: 36844135 PMCID: PMC9950870 DOI: 10.3748/wjg.v29.i6.908] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [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: 12/18/2022] [Accepted: 01/09/2023] [Indexed: 02/10/2023] Open
Abstract
Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 that manifests as a variety of clinical manifestations, including liver damage commonly detected by a hepatocellular pattern from liver function tests. Liver injury is associated with a worse prognosis overall. Conditions associated with the severity of the disease include obesity and cardiometabolic comorbidities, which are also associated with nonalcoholic fatty liver disease (NAFLD). The presence of NAFLD, similarly to obesity, is associated with an unfavourable impact on the coronavirus disease 2019 outcome. Individuals with these conditions could present with liver damage and elevated liver function tests due to direct viral cytotoxicity, systemic inflammation, ischemic or hypoxic liver damage or drug side effects. However, liver damage in the setting of NAFLD could also be attributed to a pre-existing chronic low-grade inflammation associated with surplus and dysfunctional adipose tissue in these individuals. Here we investigate the hypothesis that a pre-existing inflammatory status is exacerbated after severe acute respiratory syndrome coronavirus 2 infection, which embodies a second hit to the underestimated liver damage.
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Affiliation(s)
- Ioannis G Lempesis
- Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, B15 2TT, United Kingdom
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht 616 6200, Netherlands
| | - Eleni Karlafti
- Department of Emergency, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki 546 21, Greece
| | - Petros Papalexis
- Unit of Endocrinology, First Department of Internal Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, Athens 11527, Greece
- Department of Biomedical Sciences, University of West Attica, Athens 12243, Greece
| | - George Fotakopoulos
- Department of Neurosurgery, General University Hospital of Larisa, Larisa 41221, Greece
| | | | - Vasileios Lekakis
- Department of Gastroenterology, Laiko General Hospital, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Stavros P Papadakos
- Department of Gastroenterology, Laiko General Hospital, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
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13
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Yang R, Feng J, Wan H, Zeng X, Ji P, Zhang J. Liver injury associated with the severity of COVID-19: A meta-analysis. Front Public Health 2023; 11:1003352. [PMID: 36817905 PMCID: PMC9932800 DOI: 10.3389/fpubh.2023.1003352] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 01/17/2023] [Indexed: 02/05/2023] Open
Abstract
Background The current 2019 novel coronavirus disease (COVID-19) pandemic is a major threat to global health. It is currently uncertain whether and how liver injury affects the severity of COVID-19. Therefore, we conducted a meta-analysis to determine the association between liver injury and the severity of COVID-19. Methods A systematic search of the PubMed, Embase, and Cochrane Library databases from inception to August 12, 2022, was performed to analyse the reported liver chemistry data for patients diagnosed with COVID-19. The pooled odds ratio (OR), weighted mean difference (WMD) and 95% confidence interval (95% CI) were assessed using a random-effects model. Furthermore, publication bias and sensitivity were analyzed. Results Forty-six studies with 28,663 patients were included. The pooled WMDs of alanine aminotransferase (WMD = 12.87 U/L, 95% CI: 10.52-15.23, I 2 = 99.2%), aspartate aminotransferase (WMD = 13.98 U/L, 95% CI: 12.13-15.83, I 2 = 98.2%), gamma-glutamyl transpeptidase (WMD = 20.67 U/L, 95% CI: 14.24-27.10, I 2 = 98.8%), total bilirubin (WMD = 2.98 μmol/L, 95% CI: 1.98-3.99, I 2 = 99.4%), and prothrombin time (WMD = 0.84 s, 95% CI: 0.46-1.23, I 2 = 99.4%) were significantly higher and that of albumin was lower (WMD = -4.52 g/L, 95% CI: -6.28 to -2.75, I 2 = 99.9%) in severe cases. Moreover, the pooled OR of mortality was higher in patients with liver injury (OR = 2.72, 95% CI: 1.18-6.27, I 2 = 71.6%). Conclusions Hepatocellular injury, liver metabolic, and synthetic function abnormality were observed in severe COVID-19. From a clinical perspective, liver injury has potential as a prognostic biomarker for screening severely affected patients at early disease stages. Systematic review registration https://www.crd.york.ac.uk/prospero/, Identifier: CRD42022325206.
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Affiliation(s)
- Ruiqi Yang
- Department of Emergency Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Jihua Feng
- Department of Emergency Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Huan Wan
- Department of Emergency Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xiaona Zeng
- Department of Emergency Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Pan Ji
- Department of Emergency Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Jianfeng Zhang
- Department of Emergency Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China,Department of General Practice, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China,*Correspondence: Jianfeng Zhang ✉
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14
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Zanon M, Neri M, Pizzolitto S, Radaelli D, Concato M, Peruch M, D'Errico S. Liver pathology in COVID-19 related death and leading role of autopsy in the pandemic. World J Gastroenterol 2023; 29:200-220. [PMID: 36683722 PMCID: PMC9850946 DOI: 10.3748/wjg.v29.i1.200] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 11/14/2022] [Accepted: 12/21/2022] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Information on liver involvement in patients with coronavirus disease 2019 is currently fragmented.
AIM To highlight the pathological changes found during the autopsy of severe acute respiratory syndrome coronavirus 2 positive patients.
METHODS A systematic literature search on PubMed was carried out until June 21, 2022.
RESULTS A literature review reveals that pre-existing liver disease and elevation of liver enzyme in these patients are not common; liver enzyme elevations tend to be seen in those in critical conditions. Despite the poor expression of viral receptors in the liver, it seems that the virus is able to infect this organ and therefore cause liver damage. Unfortunately, to date, the search for the virus inside the liver is not frequent (16% of the cases) and only a small number show the presence of the virus. In most of the autopsy cases, macroscopic assessment is lacking, while microscopic evaluation of livers has revealed the frequent presence of congestion (42.7%) and steatosis (41.6%). Less frequent is the finding of hepatic inflammation or necrosis (19%) and portal inflammation (18%). The presence of microthrombi, frequently found in the lungs, is infrequent in the liver, with only 12% of cases presenting thrombotic formations within the vascular tree.
CONCLUSION To date, the greatest problem in interpreting these modifications remains the association of the damage with the direct action of the virus, rather than with the inflammation or alterations induced by hypoxia and hypovolemia in patients undergoing oxygen therapy and decompensated patients.
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Affiliation(s)
- Martina Zanon
- Department of Medical Surgical and Health Sciences, University of Trieste, Trieste 34149, Italy
| | - Margherita Neri
- Department of Medical Sciences, University of Ferrara, Ferrara 44121, Italy
| | - Stefano Pizzolitto
- Department of Pathology, Santa Maria della Misericordia University Hospital, Udine 33100, Italy
| | - Davide Radaelli
- Department of Medical Surgical and Health Sciences, University of Trieste, Trieste 34149, Italy
| | - Monica Concato
- Department of Medical Surgical and Health Sciences, University of Trieste, Trieste 34149, Italy
| | - Michela Peruch
- Department of Medical Surgical and Health Sciences, University of Trieste, Trieste 34149, Italy
| | - Stefano D'Errico
- Department of Medical Surgical and Health Sciences, University of Trieste, Trieste 34149, Italy
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15
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Saha L, Vij S, Rawat K. Liver injury induced by COVID 19 treatment - what do we know? World J Gastroenterol 2022; 28:6314-6327. [PMID: 36533104 PMCID: PMC9753058 DOI: 10.3748/wjg.v28.i45.6314] [Citation(s) in RCA: 3] [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: 09/12/2022] [Revised: 10/07/2022] [Accepted: 11/17/2022] [Indexed: 12/02/2022] Open
Abstract
The severity of coronavirus disease 2019 (COVID-19) may be correlated with the risk of liver injury development. An increasing number of studies indicate that degrees of hepatotoxicity have been associated with using some medications in the management of COVID-19 patients. However, limited studies have systematically investigated the evidence of drug-induced liver injury (DILI) in COVID-19 patients. An increasing number of studies indicate that degrees of hepatotoxicity have been associated with using some of these medications in the management of COVID-19 patients. Significantly, it was relieved after the cessation of these agents. However, to our knowledge, no studies have systematically investigated the evidence of DILI in COVID-19 patients. In this review, we discussed the association between hepatotoxicity in COVID-19 patients and the drugs used in these patients and possible mechanisms of hepatotoxicity. The currently available evidence on the association of different therapeutic agents with hepatotoxicity in COVID-19 patient was systematically reviewed.
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Affiliation(s)
- Lekha Saha
- Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Soumya Vij
- Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Kajal Rawat
- Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
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16
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Muacevic A, Adler JR. Remdesivir-Induced Liver Injury in a Patient With Coronavirus Disease 2019 and History of Congestive Hepatopathy. Cureus 2022; 14:e32353. [PMID: 36514704 PMCID: PMC9733800 DOI: 10.7759/cureus.32353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/07/2022] [Indexed: 12/14/2022] Open
Abstract
Remdesivir is an antiviral agent used as supportive care in adults with SARS-COV2-induced pneumonia. We report a case of an 81-year-old patient who developed hepatocellular acute liver injury 48 hours after initiating remdesivir. During the investigation, other causes of hepatotoxicity were excluded. A decrease in transaminases and international normalized ratio (INR) was observed 24 hours after cessation of remdesivir. An abdominal CT demonstrated hepatic congestion, retrograde hepatic venous opacification shortly after intravenous contrast injection, and dilatation of hepatic veins and inferior vena cava. We suggest congestive hepatopathy secondary to remdesivir as a possible component of liver injury.
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17
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Pal M, Muinao T, Parihar A, Roy DK, Boruah HPD, Mahindroo N, Khan R. Biosensors based detection of novel biomarkers associated with COVID-19: Current progress and future promise. BIOSENSORS & BIOELECTRONICS: X 2022; 12:100281. [PMID: 36405494 PMCID: PMC9661549 DOI: 10.1016/j.biosx.2022.100281] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 11/02/2022] [Accepted: 11/03/2022] [Indexed: 11/16/2022]
Abstract
The pandemic situation of COVID-19 has caused global alarm in health care, devastating loss of lives, strangled economy, and paralysis of normal livelihood. The high inter-individual transmission rate created havoc in the global community. Although tremendous efforts are pitching in from across the globe to understand this disease, the clinical features seemed to have a wide range including fever, cough, and fatigue are the prominent features. Congestion, rhinorrhea, sore throat, and diarrhea are other less common features observed. The challenge of this disease lies in the difficulty in maneuvering the clinical course causing severe complications. One of the major causative factors for multi-organ failure in patients with severe COVID-19 complications is systemic vasculitis and cytokine-mediated coagulation disorders. Hence, effective markers trailing the disease severity and disease prognosis are urgently required for prompt medical treatment. In this review article, we have emphasized currently identified inflammatory, hematological, immunological, and biochemical biomarkers of COVID-19. We also discussed currently available biosensors for the detection of COVID-19-associated biomarkers & risk factors and the detection methods as well as their performances. These could be effective tools for rapid and more promising diagnoses in the current pandemic situation. Effective biomarkers and their rapid, scalable, & sensitive detection might be beneficial for the prevention of serious complications and the clinical management of the disease.
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Affiliation(s)
- Mintu Pal
- Biotechnology Group, Biological Sciences and Technology Division, CSIR-North East Institute of Science and Technology (NEIST), Academy of Scientific & Innovative Research (AcSIR), CSIR-NEIST Campus, Jorhat, Assam, 785006, India
- Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Bathinda, Punjab, 151001, India
| | - Thingreila Muinao
- Biotechnology Group, Biological Sciences and Technology Division, CSIR-North East Institute of Science and Technology (NEIST), Academy of Scientific & Innovative Research (AcSIR), CSIR-NEIST Campus, Jorhat, Assam, 785006, India
| | - Arpana Parihar
- CSIR-Advanced Materials and Processes Research Institute (AMPRI), Hoshangabad Road, Bhopal, 462026, MP, India
| | - Dilip Kumar Roy
- Department of Pharmaceutical Technology, JIS University, Kolkata, 700109, India
| | - Hari Prasanna Deka Boruah
- Biotechnology Group, Biological Sciences and Technology Division, CSIR-North East Institute of Science and Technology (NEIST), Academy of Scientific & Innovative Research (AcSIR), CSIR-NEIST Campus, Jorhat, Assam, 785006, India
- Government Model College, Kaziranga, Golaghat, Assam, 785609, India
| | - Neeraj Mahindroo
- School of Pharmacy, Dr. Vishwanath Karad MIT World Peace University, Pune, Maharashtra, 411038, India
| | - Raju Khan
- CSIR-Advanced Materials and Processes Research Institute (AMPRI), Hoshangabad Road, Bhopal, 462026, MP, India
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18
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Cooper KM, Colletta A, Asirwatham AM, Moore Simas TA, Devuni D. COVID-19 associated liver injury: A general review with special consideration of pregnancy and obstetric outcomes. World J Gastroenterol 2022; 28:6017-6033. [PMID: 36405386 PMCID: PMC9669825 DOI: 10.3748/wjg.v28.i42.6017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [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: 10/24/2022] [Accepted: 10/27/2022] [Indexed: 11/15/2022] Open
Abstract
Liver injury is an increasingly recognized extra-pulmonary manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Coronavirus disease 2019 (COVID-19) associated liver injury (COVALI) is a clinical syndrome encompassing all patients with biochemical liver injury identified in the setting of SARS-CoV-2 infection. Despite profound clinical implications, its pathophysiology is poorly understood. Unfortunately, most information on COVALI is derived from the general population and may not be applicable to individuals under-represented in research, including pregnant individuals. This manuscript reviews: Clinical features of COVALI, leading theories of COVALI, and existing literature on COVALI during pregnancy, a topic not widely explored in the literature. Ultimately, we synthesized data from the general and perinatal populations that demonstrates COVALI to be a hepatocellular transaminitis that is likely induced by systemic inflammation and that is strongly associated with disease severity and poorer clinical outcome, and offered perspective on approaching transaminitis in the potentially COVID-19 positive patient in the obstetric setting.
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Affiliation(s)
- Katherine M. Cooper
- Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, United States
| | - Alessandro Colletta
- Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, United States
| | - Alison M. Asirwatham
- Department of Obstetrics and Gynecology, University of Massachusetts Chan Medical School, Worcester, MA 01605, United States
| | - Tiffany A. Moore Simas
- Department of Obstetrics and Gynecology, University of Massachusetts Chan Medical School, Worcester, MA 01605, United States
- Departments of Pediatrics, Psychiatry, and Population & Quantitative Health Sciences, University of Massachusetts Chan Medical School, Worcester, MA 01605, United States
| | - Deepika Devuni
- Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, United States
- Division of Gastroenterology and Hepatology, University of Massachusetts Chan Medical School, Worcester, MA 1605, United States
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19
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Alnamshan MM. Potential histopathological and immunological effects of SARS-CoV-2 on the liver. BRAZ J BIOL 2022; 82:e262008. [PMID: 36074418 DOI: 10.1590/1519-6984.262008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 07/05/2022] [Indexed: 12/15/2022] Open
Abstract
The coronavirus disease outbreak of 2019 (COVID-19) poses a serious threat to public health worldwide. Lung injury is the most common complication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. However, other organs, including the liver, can also be affected. Currently, there is limited evidence that liver impairment is associated with severe SARS-CoV-2 infection. Clinicians will need to determine whether liver injury is caused by an underlying liver condition, COVID-19 therapy, the virus directly, or immune-mediated inflammation or represents a complicated disease course in the context of COVID-19. To address the scarcity of data on histopathological changes and immunological effects on the liver with COVID-19 positivity, we analyze and summarize recent findings. We searched PubMed, Medline, Google Scholar, Science Direct, Scopus, and Web of Science databases up to December 1, 2021, identifying published studies with the search terms "Histopathology in COVID-19," "COVID-19," "Pathological changes in liver in COVID-19," "Liver pathology in COVID-19," "immunological effects in liver in COVID-19," and "SARS-CoV-2." This concise review will aid clinicians and researchers in better understanding the tissue histopathology and immunological consequences of SARS-CoV-2 on the liver, enabling improved care planning and avoiding future dangers.
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Affiliation(s)
- M M Alnamshan
- Imam Abdulrahman Bin Faisal University, College of Science, Department of Biology, Dammam, Saudi Arabia
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20
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Yilmaz AE. How reliable are the multiple comparison methods for odds ratio? J Appl Stat 2022; 49:3141-3163. [PMID: 36035608 PMCID: PMC9415621 DOI: 10.1080/02664763.2022.2104229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/16/2022]
Abstract
The homogeneity tests of odds ratios are used in clinical trials and epidemiological investigations as a preliminary step of meta-analysis. In recent studies, the severity or mortality of COVID-19 in relation to demographic characteristics, comorbidities, and other conditions has been popularly discussed by interpreting odds ratios and using meta-analysis. According to the homogeneity test results, a common odds ratio summarizes all of the odds ratios in a series of studies. If the aim is not to find a common odds ratio, but to find which of the sub-characteristics/groups is different from the others or is under risk, then the implementation of a multiple comparison procedure is required. In this article, the focus is placed on the accuracy and reliability of the homogeneity of odds ratio tests for multiple comparisons when the odds ratios are heterogeneous at the omnibus level. Three recently proposed multiple comparison tests and four homogeneity of odds ratios tests with six adjustment methods to control the type-I error rate are considered. The reliability and accuracy of the methods are discussed in relation to COVID-19 severity data associated with diabetes on a country-by-country basis, and a simulation study to assess the powers and type-I error rates of the tests is conducted.
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21
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Harapan H, Fajar JK, Supriono S, Soegiarto G, Wulandari L, Seratin F, Prayudi NG, Dewi DP, Monica Elsina MT, Atamou L, Wiranata S, Aprianto DP, Friska E, Sari Firdaus DF, Alaidin M, Wardhani FA, Husnah M, Hidayati NW, Hendriyanti Y, Wardani K, Evatta A, Manugan RA, Pradipto W, Rahmawati A, Tamara F, Mahendra AI, Nainu F, Santoso B, Irawan Primasatya CA, Tjionganata N, Budiman HA. The prevalence, predictors and outcomes of acute liver injury among patients with COVID-19: A systematic review and meta-analysis. Rev Med Virol 2022; 32:e2304. [PMID: 34643006 PMCID: PMC8646502 DOI: 10.1002/rmv.2304] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 09/25/2021] [Accepted: 09/28/2021] [Indexed: 01/09/2023]
Abstract
The data on the predictors and prognosis of acute liver injury (ALI) among patients in coronavirus disease 2019 (COVID-19) patients are limited. The aim of this study was to determine the prevalence, predictors and outcomes of ALI among patients with COVID-19. A systematic review was conducted up to 10 June 2021. The relevant papers were searched from PubMed, Embase, Cochrane and Web of Science, and the data were analysed using a Z test. A total of 1331 papers were identified and 16 papers consisting of 1254 COVID-19 with ALI and 4999 COVID-19 without ALI were analysed. The cumulative prevalence of ALI among patients with COVID-19 was 22.8%. Male and having low lymphocyte levels were more likely to be associated with ALI compared with female and having higher lymphocyte level, odds ratio (OR): 2.70; 95% confidence interval (CI): 2.03, 3.60 and mean difference (MD) -125; 95% CI: -207, -43, respectively. COVID-19 patients with ALI had higher risk of developing severe COVID-19 compared with those without ALI (OR: 3.61; 95% CI: 2.60, 5.02). Our findings may serve as the additional evaluation for the management of ALI in COVID-19 patients.
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Affiliation(s)
- Harapan Harapan
- Medical Research UnitSchool of MedicineUniversitas Syiah KualaBanda AcehIndonesia
- Tropical Disease CentreSchool of MedicineUniversitas Syiah KualaBanda AcehIndonesia
- Department of MicrobiologySchool of MedicineUniversitas Syiah KualaBanda AcehIndonesia
| | - Jonny Karunia Fajar
- Brawijaya Internal Medicine Research CentreDepartment of Internal MedicineFaculty of MedicineUniversitas BrawijayaMalangIndonesia
| | - Supriono Supriono
- Department of Internal MedicineDivision of Gastro‐Entero‐HepatologyFaculty of MedicineUniversitas BrawijayaMalangIndonesia
| | - Gatot Soegiarto
- Department of Internal MedicineDivision of Allergy & ImmunologyUniversitas AirlanggaSurabayaIndonesia
| | - Laksmi Wulandari
- Department of Pulmonology and Respiratory MedicineUniversitas AirlanggaSurabayaIndonesia
| | - Fiha Seratin
- Department of PaediatricFaculty of MedicineUniversitas PadjajaranBandungIndonesia
| | - Nyoman Gede Prayudi
- Department of UrologyFaculty of MedicineUniversitas BrawijayaMalangIndonesia
| | | | | | | | | | | | - Erlin Friska
- Faculty of MedicineUniversitas IndonesiaDepokIndonesia
| | | | - Makdum Alaidin
- Department of NursingFaculty of MedicineUniversitas DiponegoroSemarangIndonesia
| | | | - Milda Husnah
- Master Program of BiologyFaculty of Mathematics and Natural SciencesUniversitas Syiah KualaBanda AcehIndonesia
| | | | | | - Kristia Wardani
- Brawijaya Internal Medicine Research CentreDepartment of Internal MedicineFaculty of MedicineUniversitas BrawijayaMalangIndonesia
| | - Arde Evatta
- Brawijaya Internal Medicine Research CentreDepartment of Internal MedicineFaculty of MedicineUniversitas BrawijayaMalangIndonesia
| | - Reizal Audi Manugan
- Brawijaya Internal Medicine Research CentreDepartment of Internal MedicineFaculty of MedicineUniversitas BrawijayaMalangIndonesia
| | - Wiryawan Pradipto
- Brawijaya Internal Medicine Research CentreDepartment of Internal MedicineFaculty of MedicineUniversitas BrawijayaMalangIndonesia
| | - Ade Rahmawati
- Brawijaya Internal Medicine Research CentreDepartment of Internal MedicineFaculty of MedicineUniversitas BrawijayaMalangIndonesia
| | - Fredo Tamara
- Brawijaya Internal Medicine Research CentreDepartment of Internal MedicineFaculty of MedicineUniversitas BrawijayaMalangIndonesia
| | - Aditya Indra Mahendra
- Brawijaya Internal Medicine Research CentreDepartment of Internal MedicineFaculty of MedicineUniversitas BrawijayaMalangIndonesia
| | - Firzan Nainu
- Faculty of PharmacyHasanuddin UniversityMakassarIndonesia
| | - Budi Santoso
- Department of Internal MedicineRSUD BangilPasuruanIndonesia
| | | | - Nindy Tjionganata
- Department of Internal MedicineFaculty of MedicineUniversitas AirlanggaSurabayaIndonesia
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22
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Hadid-Beurrier L, Cohen A, Habib-Geryes B, Voicu S, Malissin I, Deye N, Mégarbane B, Bousson V. Cumulative Radiation Exposure in Covid-19 Patients Admitted to the Intensive Care Unit. Radiat Res 2022; 197:605-612. [DOI: 10.1667/rade-21-00203.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 02/11/2022] [Indexed: 12/15/2022]
Abstract
Medical imaging plays a major role in coronavirus disease-2019 (COVID-19) patient diagnosis and management. However, the radiation dose received from medical procedures by these patients has been poorly investigated. We aimed to estimate the cumulative effective dose (CED) related to medical exposure in COVID-19 patients admitted to the intensive care unit (ICU) in comparison to the usual critically ill patients. We designed a descriptive cohort study including 90 successive ICU COVID-19 patients admitted between March and May 2020 and 90 successive non-COVID-19 patients admitted between March and May 2019. In this study, the CED resulting from all radiological examinations was calculated and clinical characteristics predictive of higher exposure risk identified. The number of radiological examinations was 12.0 (5.0–26.0) [median (interquartile range) in COVID-19 vs.4.0 (2.0–8.0) in non-COVID-19 patient (P < 0.001)]. The CED during a four-month period was 4.2 mSv (1.9–11.2) in the COVID-19 vs. 1.2 mSv (0.13–6.19) in the non-COVID-19 patients (P < 0.001). In the survivors, the CED in COVID-19 vs. non-COVID-19 patients was ≥100 mSv in 3% vs. 0%, 10–100 mSv in 23% vs. 15%, 1–10 mSv in 56% vs. 30% and <1 mSv in 18% vs. 55%. The CED (P < 0.001) and CED per ICU hospitalization day (P = 0.004) were significantly higher in COVID-19 than non-COVID-19 patients. The CED correlated significantly with the hospitalization duration (r = 0.45, P < 0.001) and the number of conventional radiological examinations (r = 0.8, P < 0.001). To conclude, more radiological examinations were performed in critically ill COVID-19 patients than non-COVID-19 patients resulting in higher CED. In COVID-19 patients, contribution of strategies to limit CED should be investigated in the future.
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Affiliation(s)
- Lama Hadid-Beurrier
- Department of Medical Physics and Radiation Protection, Lariboisière Hospital, APHP, Paris, France
- Department of Skeletal and Visceral Radiology, Lariboisière Hospital, APHP, Paris University, Paris, France
| | - Axel Cohen
- Department of Skeletal and Visceral Radiology, Lariboisière Hospital, APHP, Paris University, Paris, France
| | - Bouchra Habib-Geryes
- Department of Medical Physics, Necker-Enfants-Malades Hospital, APHP, Paris, France
| | - Sébastian Voicu
- Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Federation of Toxicology, APHP, INSERM UMRS-1144, Paris University, Paris, France
| | - Isabelle Malissin
- Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Federation of Toxicology, APHP, INSERM UMRS-1144, Paris University, Paris, France
| | - Nicolas Deye
- Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Federation of Toxicology, APHP, INSERM UMRS-1144, Paris University, Paris, France
| | - Bruno Mégarbane
- Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Federation of Toxicology, APHP, INSERM UMRS-1144, Paris University, Paris, France
| | - Valérie Bousson
- Department of Skeletal and Visceral Radiology, Lariboisière Hospital, APHP, Paris University, Paris, France
- Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7052, Université de Paris, Paris, France
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23
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Krishnasamy N, Rajendran K, Barua P, Ramachandran A, Panneerselvam P, Rajaram M. Elevated Liver Enzymes along with Comorbidity Is a High Risk Factor for COVID-19 Mortality: A South Indian Study on 1,512 Patients. J Clin Transl Hepatol 2022; 10:120-127. [PMID: 35233380 PMCID: PMC8845151 DOI: 10.14218/jcth.2020.00100] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 01/30/2021] [Accepted: 05/20/2021] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND AND AIMS Liver enzyme abnormalities in coronavirus 2019 (COVID-19) are being addressed in the literature. The predictive risk of elevated liver enzymes has not been established for COVID-19 mortality. In this study, we hypothesized that elevated liver enzymes at admission can predict the outcome of COVID-19 disease with other known indicators, such as comorbidities. METHODS This retrospective study included all the consecutive hospitalized patients with confirmed COVID-19 disease from March 4th to May 31st, 2020. The study was conducted in Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu, India. We assessed demography, clinical variables, COVID-19 severity, laboratory parameters, and outcome. RESULTS We included 1,512 patients, and median age was 47 years (interquartile range: 34-60) with 36.9% being female. Liver enzyme level (aspartate aminotransferase and/or alanine aminotransferase) was elevated in 450/1,512 (29.76%) patients. Comorbidity was present in 713/1,512 (47.16%) patients. Patients with liver enzymes' elevation and presence of comorbidity were older, more frequently hospitalized in ICU and had more severe symptoms of COVID-19 at the time of admission. Presence of liver enzymes' elevation with comorbidity was a high risk factor for death (OR: 5.314, 95% CI: 2.278-12.393), as compared to patients with presence of comorbidity (OR: 4.096, 95% CI: 1.833-9.157). CONCLUSIONS Comorbidity combined with liver enzymes' elevation at presentation independently increased the risk of death in COVID-19 by at least 5-fold.
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Affiliation(s)
- Narayanasamy Krishnasamy
- Institute of Hepatobiliary Sciences, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu, India
- Correspondence to: Narayanasamy Krishnasamy, Institute of Hepatobiliary Sciences, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu 600003, India. Tel: +91-9841170145, Fax: +91-4425305115, E-mail: ; Karthick Rajendran, Multidisciplinary Research Unit, Madras Medical College, Chennai, Tamil Nadu 600003, India. ORCID: https://orcid.org/0000-0003-3938-3347. Tel: +91-9790787578, Fax: +91-4425305115, E-mail:
| | - Karthick Rajendran
- Multidisciplinary Research Unit (MRU), Madras Medical College, Chennai, Tamil Nadu, India
- Correspondence to: Narayanasamy Krishnasamy, Institute of Hepatobiliary Sciences, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu 600003, India. Tel: +91-9841170145, Fax: +91-4425305115, E-mail: ; Karthick Rajendran, Multidisciplinary Research Unit, Madras Medical College, Chennai, Tamil Nadu 600003, India. ORCID: https://orcid.org/0000-0003-3938-3347. Tel: +91-9790787578, Fax: +91-4425305115, E-mail:
| | - Parimita Barua
- Institute of Hepatobiliary Sciences, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu, India
| | - Arunkumar Ramachandran
- Multidisciplinary Research Unit (MRU), Madras Medical College, Chennai, Tamil Nadu, India
| | | | - Muthukumaran Rajaram
- Multidisciplinary Research Unit (MRU), Madras Medical College, Chennai, Tamil Nadu, India
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24
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COVID-19 and liver dysfunction: Epidemiology, association and potential mechanisms. Clin Res Hepatol Gastroenterol 2022; 46:101793. [PMID: 34428501 PMCID: PMC8380064 DOI: 10.1016/j.clinre.2021.101793] [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: 04/13/2021] [Revised: 05/21/2021] [Accepted: 08/05/2021] [Indexed: 02/07/2023]
Abstract
Currently, there have been more than one hundred million confirmed cases of coronavirus disease 2019 (COVID-19), with two million deaths worldwide. This has caused a huge medical burden. Severe COVID-19 patients can experience multi-organ damage, including cardiac injury, kidney injury, and liver injury. About 2.0%-4.9% of COVID-19 cases involve patients with preexisting liver diseases. Additionally, preexisting liver diseases were reported and associated with severity (odds ratio (OR) or risk ratio (RR) = 1.48-1.70) and mortality (OR or RR = 1.08-2.65) among COVID-19 patients. Furthermore, the prevalence of liver injury was 16%-29% in COVID-19 patients. Higher prevalence of liver injury may worsen prognosis in patients (severity: OR or RR = 1.9-2.6; mortality: OR or RR = 1.1-4.0). The mechanisms of this association between liver injury and severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection are complex, including direct cholangiocyte damage induced by SARS-COV-2, cytokine storm, and drug-induced liver injury. In particular, drug-induced liver injury may be the most important reason. This review discusses the epidemiology of COVID-19 and liver dysfunction as well as potential mechanisms underlying the association between COVID-19 and liver dysfunction or other preexisting liver diseases. However, the association between preexisting liver diseases and COVID-19 prognosis and potential mechanisms underlying these associations require further prospective studies.
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25
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Mohammed SA, Eid KM, Anyiam FE, Wadaaallah H, Muhamed MAM, Morsi MH, Dahman NBH. Liver injury with COVID-19: laboratory and histopathological outcome-systematic review and meta-analysis. EGYPTIAN LIVER JOURNAL 2022; 12:9. [PMID: 35096428 PMCID: PMC8781706 DOI: 10.1186/s43066-022-00171-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 01/02/2022] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been predominantly linked to respiratory distress syndrome, but hepatic injury has also been reported. The mechanism of liver injury is poorly understood.This review aimed to systematically review the current data through laboratory tests and liver tissue pathology to ascertain the correlation of liver involvement in SARS-CoV-2 infection patients. METHODS The PubMed, Scopus, Science Direct, and Web of Science databases were searched systematically. We included peer-reviewed published papers available online as clinical cases, cohort studies, and retrospective studies, for both in vitro and in vivo human studies. Independent extraction of the data was done by two independent authors. RESULTS A total of 15 articles were finally included in the systematic review process and meta-analysis after exclusion of studies that did not meet the eligibility criteria, summarized in a PRISMA flow diagram.The meta-analysis showed that patients with underlying abnormal liver function and/or histopathological finding had a statistically significant 8.08 times higher odds of severe COVID-19 outcomes when data from the individual studies were pooled (OR 8.08; 95% CI,3.43, 19.03; p = 0.00001). Five of these studies showed histopathological changes on autopsy from cases with severe COVID-19, and in four of these five studies, the histopathology was associated with a history of abnormal liver function after affection with COVID-19. SHORT CONCLUSION The study observed that the severity of COVID-19 was associated with more patients with aberrant liver function tests.
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Affiliation(s)
| | - Khalid M Eid
- Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, Egypt
| | - Felix Emeka Anyiam
- Centre for Health and Development, University of Port Harcourt, Port Harcourt, Nigeria
| | - Hazem Wadaaallah
- Biomedical Physics Department, Faculty of Science, Helwan University, Cairo, Egypt
| | | | - Maha Hosni Morsi
- Misr University for Science and Technology, 6th of October City, Egypt
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26
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Kayaaslan B, Guner R. COVID-19 and the liver: A brief and core review. World J Hepatol 2021; 13:2013-2023. [PMID: 35070005 PMCID: PMC8727220 DOI: 10.4254/wjh.v13.i12.2013] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 06/23/2021] [Accepted: 11/27/2021] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 has a wide range of clinical spectrum from asymptomatic infection to severe infection resulting in death within a short time. Currently, it is known that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) does not only cause a respiratory tract infection but a more complicated disease that can lead to multiple system involvement including the liver. Herein, we evaluate the epidemiology, the impact of liver injury/ dysfunction on disease prognosis, the pathophysiological mechanisms and management of liver injury. More than one-fourth of the patients have abnormal liver function tests, mostly a mild-to-moderate liver dysfunction. Liver injury is significantly associated with a poor clinical outcome. Direct cytotoxic effect of SARS-CoV-2, the immune response ("cytokine storm"), the complications related to the disease, and drugs used in the treatments are the pathophysiological mechanisms responsible for liver injury. However, the exact mechanism is not yet clearly explained. The binding of SARS-CoV-2 to the angiotensin-converting enzyme 2 receptors and entering the hepatocyte and cholangiocytes can cause cytotoxic effects on the liver. Excessive immune response has an important role in disease progression and causes acute respiratory distress syndrome and multi-organ failures accompanied by liver injury. Treatment drugs, particularly lopinavir/ritonavir, remdesivir and antibiotics are a frequent reason for liver injury. The possible reasons should be meticulously investigated and resolved.
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Affiliation(s)
- Bircan Kayaaslan
- Department of Infectious Disease and Clinical Microbiology, Ankara City Hospital, Ankara Yildirim Beyazit University, Ankara 06800, Turkey.
| | - Rahmet Guner
- Department of Infectious Disease and Clinical Microbiology, Ankara City Hospital, Ankara Yildirim Beyazit University, Ankara 06800, Turkey
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27
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Liemarto AK, Budiono BP, Chionardes MA, Oliviera I, Rahmasiwi A. Liver abscess with necrosis in post COVID-19: A case report. Ann Med Surg (Lond) 2021; 72:103107. [PMID: 34840781 PMCID: PMC8608684 DOI: 10.1016/j.amsu.2021.103107] [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: 10/26/2021] [Revised: 11/21/2021] [Accepted: 11/21/2021] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION Coronavirus disease 2019 (COVID-19) is an acute respiratory tract infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2). Recent evidences mentioned the possibility of COVID-19 as a systemic infectious and inflammatory disease. Signs and symptoms of liver and gastrointestinal system are often found in post-acute COVID-19 patients. However, there are only few data found about liver abscess and necrosis in post COVID-19 patients. CASE PRESENTATION A 49-year-old man admitted to the hospital with dyspnea, nausea, loss of appetite and epigastric pain, post confirmed SARS CoV-2 severe pneumonia 1 month ago in ICU with noninvasive ventilator (NIV), enoxaparin, tocilizumab, azithromycin, levofloxacin, hydroxychloroquine, and no preexisting liver condition. Swab PCR result was negative. The result of abdominal computed tomography (CT) scan with contrast was liver abscess formation with hemorrhages measuring about 16 × 12 × 11 cm & 10 × 9x9 cm occupying most of the right lobe liver. The patient underwent exploratory laparotomy, there were multiple liver abscesses in segment 8 with parenchymal liver necrosis and abscesses in segment 7 of liver. Necrosectomy and liver abscess drainage was performed. CLINICAL DISCUSSION Pathophysiology of liver damage in post COVID-19 are direct cytotoxicity of SARS-CoV2, immune-mediated due to severe systemic inflammatory response syndrome (SIRS) in COVID-19, hypoxemia, vascular changes due to coagulopathy, endothelitis or congestion from right heart failure, and drug-induced liver injury (DILI). CONCLUSION The possible pathophysiology of liver abscess and necrosis in post COVID-19 should be considered in monitoring and management for both COVID-19 patients and post COVID-19 patients.
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Affiliation(s)
- Aldrich Kurniawan Liemarto
- Intensive Care Unit, Columbia Asia Hospital, Semarang, Indonesia
- Department of Internal Medicine, Columbia Asia Hospital, Semarang, Indonesia
| | - Bernadus Parish Budiono
- Intensive Care Unit, Columbia Asia Hospital, Semarang, Indonesia
- Department of Digestive Surgery, Columbia Asia Hospital, Semarang, Indonesia
| | | | - Ivona Oliviera
- Intensive Care Unit, Columbia Asia Hospital, Semarang, Indonesia
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28
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Rashedi S, Keykhaei M, Pazoki M, Ashraf H, Najafi A, Kafan S, Peirovi N, Najmeddin F, Jazayeri SA, Kashani M, Moharari RS, Montazeri M. Clinical significance of prognostic nutrition index in hospitalized patients with COVID-19: Results from single-center experience with systematic review and meta-analysis. Nutr Clin Pract 2021; 36:970-983. [PMID: 34270114 PMCID: PMC8441695 DOI: 10.1002/ncp.10750] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND We aimed to ascertain risk indicators of in-hospital mortality and severity as well as to provide a comprehensive systematic review and meta-analysis to investigate the prognostic significance of the prognostic nutrition index (PNI) as a predictor of adverse outcomes in hospitalized coronavirus disease 2019 (COVID-19) patients. METHODS In this cross-sectional study, we studied patients with COVID-19 who were referred to our hospital from February 16 to November 1, 2020. Patients with either a real-time reverse-transcriptase polymerase chain reaction test that was positive for COVID-19 or high clinical suspicion based on the World Health Organization (WHO) interim guidance were enrolled. A parallel systematic review/meta-analysis (in PubMed, Embase, and Web of Science) was performed. RESULTS A total of 504 hospitalized COVID-19 patients were included in this study, among which 101 (20.04%) patients died during hospitalization, and 372 (73.81%) patients were categorized as severe cases. At a multivariable level, lower PNI, higher lactate dehydrogenase (LDH), and higher D-dimer levels were independent risk indicators of in-hospital mortality. Additionally, patients with a history of diabetes, lower PNI, and higher LDH levels had a higher tendency to develop severe disease. The meta-analysis indicated the PNI as an independent predictor of in-hospital mortality (odds ratio [OR] = 0.80; P < .001) and disease severity (OR = 0.78; P = .009). CONCLUSION Our results emphasized the predictive value of the PNI in the prognosis of patients with COVID-19, necessitating the implementation of a risk stratification index based on PNI values in hospitalized patients with COVID-19.
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Affiliation(s)
- Sina Rashedi
- School of MedicineTehran University of Medical SciencesTehranIran
| | - Mohammad Keykhaei
- Non‐Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences InstituteTehran University of Medical SciencesTehranIran
| | - Marzieh Pazoki
- Department of Pulmonary Medicine, Sina HospitalTehran University of Medical SciencesTehranIran
| | - Haleh Ashraf
- Research Development Center, Sina HospitalTehran University of Medical SciencesTehranIran,Cardiac Primary Prevention Research Center (CPPRC), Cardiovascular Diseases Research InstituteTehran University of Medical SciencesTehranIran
| | - Atabak Najafi
- Department of Anesthesiology and Critical CareTehran University of Medical Sciences, Sina HospitalTehranIran
| | - Samira Kafan
- Department of Pulmonary Medicine, Sina HospitalTehran University of Medical SciencesTehranIran
| | - Niloufar Peirovi
- School of MedicineTehran University of Medical SciencesTehranIran
| | - Farhad Najmeddin
- Department of Clinical Pharmacy, Faculty of PharmacyTehran University of Medical SciencesTehranIran
| | | | - Mehdi Kashani
- Research Development Center, Sina HospitalTehran University of Medical SciencesTehranIran
| | | | - Mahnaz Montazeri
- Department of Infectious Diseases, Sina HospitalTehran University of Medical SciencesTehranIran
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Wilairatana P, Masangkay FR, Kotepui KU, Milanez GDJ, Kotepui M. Prevalence and characteristics of malaria among COVID-19 individuals: A systematic review, meta-analysis, and analysis of case reports. PLoS Negl Trop Dis 2021; 15:e0009766. [PMID: 34597315 PMCID: PMC8486116 DOI: 10.1371/journal.pntd.0009766] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 08/26/2021] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND The world population is currently at a very high risk of Coronavirus disease-2019 (COVID-19), caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). People who live in malaria-endemic areas and get infected by SARS-CoV-2 may be at increased risk of severe COVID-19 or unfavorable disease outcomes if they ignore their malaria status. Therefore, the present study aimed to synthesize, qualitatively and quantitatively, information on the prevalence and characteristics of malaria infection among COVID-19-infected individuals. The findings will help us better understand this particular comorbidity during the COVID-19 pandemic. METHODS The systematic review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) with the identification number: CRD42021247521. We searched for studies reporting on the coinfection of COVID-19 and malaria in PubMed, Web of Science, and Scopus from inception to March 27, 2021 using Medical Subject Headings (MeSH) terms. The study's methodological quality in the search output was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Tools for cross-sectional study. The pooled prevalence of Plasmodium spp. infection among patients infected with COVID-19 was estimated using the random effect model and then graphically presented as forest plots. The heterogeneity among the included studies was assessed using Cochrane Q and I2 statistics. The characteristics of patients co-infected with COVID-19 and malaria were derived from case reports and series and were formally analyzed using simple statistics. RESULTS Twelve of 1,207 studies reporting the coinfection of COVID-19 and malaria were selected for further analysis. Results of quantitative synthesis show that the pooled prevalence of Plasmodium spp. infection (364 cases) among COVID-19 individuals (1,126 cases) is 11%, with a high degree of heterogeneity (95% CI: 4%-18%, I2: 97.07%, 5 studies). Most of the coinfections were reported in Nigeria (336 cases), India (27 cases), and the Democratic Republic of Congo (1 case). Results of qualitative synthesis indicate that patients with coinfection are typically symptomatic at presentation with mild or moderate parasitemia. An analysis of case reports and series indicates that co-infected individuals often display thrombocytopenia, lymphopenia, and elevated bilirubin levels. Among four patients (30%) who required treatment with intravenous artesunate, one experienced worsened clinical status after administering the drug. One serious outcome of coinfection involved a pregnant woman who experienced fetal abortion due to the initial misdiagnosis of malaria. CONCLUSIONS All individuals in malaria-endemic regions who are febrile or display symptoms of COVID-19 should be evaluated for malaria to avoid serious complications. Further prospective studies are required to investigate the burden and outcomes of COVID-19 in malaria-endemic regions. Prompt management is required to prevent serious outcomes in individuals co-infected with COVID-19 and malaria.
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Affiliation(s)
- Polrat Wilairatana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Frederick Ramirez Masangkay
- Department of Medical Technology, Institute of Arts and Sciences, Far Eastern University-Manila, Manila, Philippines
| | - Kwuntida Uthaisar Kotepui
- Medical Technology, School of Allied Health Sciences, Walailak University, Tha Sala, Nakhon Si Thammarat, Thailand
| | - Giovanni De Jesus Milanez
- Department of Medical Technology, Faculty of Pharmacy, University of Santo Tomas, Manila, Philippines
| | - Manas Kotepui
- Medical Technology, School of Allied Health Sciences, Walailak University, Tha Sala, Nakhon Si Thammarat, Thailand
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Ortiz GX, Lenhart G, Becker MW, Schwambach KH, Tovo CV, Blatt CR. Drug-induced liver injury and COVID-19: A review for clinical practice. World J Hepatol 2021; 13:1143-1153. [PMID: 34630881 PMCID: PMC8473488 DOI: 10.4254/wjh.v13.i9.1143] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 05/18/2021] [Accepted: 08/18/2021] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) consists of a systemic disease that can present many complications. The infection presents broad clinical symptoms and a high rate of transmissibility. In addition to severe acute respiratory syndrome, the patients manifest complications beyond the respiratory system. The frequency of liver damage in COVID-19 patients ranges from 14.8% to 53% of patients. One should pay attention to drug-induced liver injury (DILI) in patients with COVID-19, especially considering the off-label use of drugs in prophylactic and therapeutic regimens applied on large scales. This review aims to present relevant information on the medication used so far in COVID-19 patients and its possible hepatotoxicity. We reviewed liver damage in patients with COVID-19 on PubMed and Virtual Health Library to investigate DILI cases. Four studies were selected, involving the medicines remdesivir, tocilizumab and a pharmacovigilance analysis study. The hepatotoxicity profile of drugs presented in the literature considers use in accordance to usual posology standards for treatment. However, drugs currently used in the management of COVID-19 follow different dosages and posology than those tested by the pharmaceutical industry. The deficiency of uniformity and standardization in the assessment of hepatotoxicity cases hinders the publication of information and the possibility of comparing information among healthcare professionals. It is suggested that severe liver injury in COVID-19 patients should be reported in pharmacovigilance institutions, and physicians should pay attention to any considerable abnormal liver test elevation as it can demonstrate unknown drug hepatotoxicity. Liver disorders in COVID-19 patients and the use of several concomitant off-label medications - with a potential risk of further damaging the liver - should at least be a warning sign for rapid identification and early intervention, thus preventing liver damage from contributing to severe impairment in patients.
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Affiliation(s)
- Gabriela Xavier Ortiz
- Graduate Program in Medicine Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Rio Grande do Sul, Brazil
| | - Gabriele Lenhart
- Multiprofessional Residency Integrated in Health, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Rio Grande do Sul, Brazil
| | - Matheus William Becker
- Graduate Program in Medicine Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Rio Grande do Sul, Brazil.
| | - Karin Hepp Schwambach
- Graduate Program in Medicine Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Rio Grande do Sul, Brazil
| | - Cristiane Valle Tovo
- Internal Medicine Department, Graduate Program in Medicine-Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Rio Grande do Sul, Brazil
| | - Carine Raquel Blatt
- Pharmacoscience Department, Graduate Program in Medicine-Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Rio Grande do Sul, Brazil
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Sodeifian F, Seyedalhosseini ZS, Kian N, Eftekhari M, Najari S, Mirsaeidi M, Farsi Y, Nasiri MJ. Drug-Induced Liver Injury in COVID-19 Patients: A Systematic Review. Front Med (Lausanne) 2021; 8:731436. [PMID: 34616757 PMCID: PMC8488138 DOI: 10.3389/fmed.2021.731436] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Accepted: 08/25/2021] [Indexed: 02/06/2023] Open
Abstract
Introduction: The severity of COVID-19 may be correlated with the risk of liver injury development. An increasing number of studies indicate that degrees of hepatotoxicity has been associated with using some medications in the management of COVID-19 patients. However, limited studies had systematically investigated the evidence of drug-induced liver injury (DILI) in COVID-19 patients. Thus, this study aimed to examine DILI in COVID-19 patients. Methods: A systematic search was carried out in PubMed/Medline, EMBASE, and Web of Science up to December 30, 2020. Search items included "SARS-CoV-2", "Coronavirus," COVID-19, and liver injury. Results: We included 22 related articles. Among included studies, there was five case report, five case series, four randomizes control trial (RCT), seven cohort studies, and one cross-sectional study. The drugs included in this systematic review were remdesivir, favipiravir, tocilizumab, hydroxychloroquine, and lopinavir/ritonavir. Among included studies, some studies revealed a direct role of drugs, while others couldn't certainly confirm that the liver injury was due to SARS-CoV-2 itself or administration of medications. However, a significant number of studies reported that liver injury could be attributable to drug administration. Discussion: Liver injury in COVID-19 patients could be caused by the virus itself or the administration of some types of drug. Intensive liver function monitoring should be considered for patients, especially patients who are treated with drugs such as remdesivir, lopinavir/ritonavir, and tocilizumab.
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Affiliation(s)
- Fatemeh Sodeifian
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Sadat Seyedalhosseini
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Naghmeh Kian
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahya Eftekhari
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shaghayegh Najari
- School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Mirsaeidi
- Division of Pulmonary and Critical Care, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, United States
- Department of Pulmonary and Critical Care, Miami VA Medical Center, Miami, FL, United States
| | - Yeganeh Farsi
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Javad Nasiri
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Malekifar P, Pakzad R, Shahbahrami R, Zandi M, Jafarpour A, Rezayat SA, Akbarpour S, Shabestari AN, Pakzad I, Hesari E, Farahani A, Soltani S. Viral Coinfection among COVID-19 Patient Groups: An Update Systematic Review and Meta-Analysis. BIOMED RESEARCH INTERNATIONAL 2021; 2021:5313832. [PMID: 34485513 PMCID: PMC8416381 DOI: 10.1155/2021/5313832] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 08/10/2021] [Indexed: 12/23/2022]
Abstract
BACKGROUND Coinfections have a potential role in increased morbidity and mortality rates during pandemics. Our investigation is aimed at evaluating the viral coinfection prevalence in COVID-19 patients. METHODS We systematically searched scientific databases, including Medline, Scopus, WOS, and Embase, from December 1, 2019, to December 30, 2020. Preprint servers such as medRxiv were also scanned to find other related preprint papers. All types of studies evaluating the viral coinfection prevalence in COVID-19 patients were considered. We applied the random effects model to pool all of the related studies. RESULTS Thirty-three studies including 10484 patients were identified. The viral coinfection estimated pooled prevalence was 12.58%; 95% CI: 7.31 to 18.96). Blood viruses (pooled prevalence: 12.48%; 95% CI: 8.57 to 16.93) had the most frequent viral coinfection, and respiratory viruses (pooled prevalence: 4.32%; 95% CI: 2.78 to 6.15) had less frequent viral coinfection. The herpesvirus pooled prevalence was 11.71% (95% CI: 3.02 to 24.80). Also, the maximum and minimum of viral coinfection pooled prevalence were in AMRO and EMRO with 15.63% (95% CI: 3.78 to 33.31) and 7.05% (95% CI: 3.84 to 11.07), respectively. CONCLUSION The lowest rate of coinfection belonged to respiratory viruses. Blood-borne viruses had the highest coinfection rate. Our results provide important data about the prevalence of blood-borne viruses among COVID-19 patients which can be critical when it comes to their treatment procedure.
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Affiliation(s)
- Pooneh Malekifar
- Department of Epidemiology, School of Public Health, Tehran University Medical Sciences, Tehran, Iran
| | - Reza Pakzad
- Department of Epidemiology, Faculty of Health, Ilam University Medical Sciences, Ilam, Iran
- Student Research Committee, Ilam University Medical Sciences, Ilam, Iran
| | - Ramin Shahbahrami
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran
| | - Milad Zandi
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Jafarpour
- Gerash Amir-al-Momenin Medical and Educational Center, Gerash University of Medical Sciences, Gerash, Iran
| | - Sara Akhavan Rezayat
- Department of Management & Health Economics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Samaneh Akbarpour
- Occupational Sleep Research Center, Baharloo Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Namazi Shabestari
- Department of Geriatric Medicine, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Iraj Pakzad
- Department of Microbiology, School of Medicine, Ilam University Medical Sciences, Ilam, Iran
| | - Elahe Hesari
- Department of Epidemiology, School of Public Health, Tehran University Medical Sciences, Tehran, Iran
| | - Abbas Farahani
- Infectious and Tropical Diseases Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Saber Soltani
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
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Kravchuk YA. Features of management of patients with liver diseases in the conditions of the COVID-19 pandemic. RUSSIAN MILITARY MEDICAL ACADEMY REPORTS 2021; 40:57-62. [DOI: 10.17816/rmmar76270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
Abstract
Liver dysfunction is common with COVID-19 infection, and the prevalence is higher in men as well as in the elderly. Manifestations of liver damage such as high aspartate aminotransferase and alanine aminotransferase activity, increased bilirubin levels, low albumin levels, and prolonged prothrombin time are associated with severe COVID-19 infection. Mortality in patients with diffuse liver diseases without cirrhosis with COVID-19 infection was 12 %, in the presence of liver cirrhosis up to 40%, decompensated liver cirrhosis up to 4363%. The mechanisms of liver damage in COVID-19 include direct hepatotoxicity and indirect liver damage (due to systemic inflammation with impaired immunity, sepsis, hypoxia, ischemia, coagulopathy, endotheliitis, right ventricular failure, worsening of the course of existing liver diseases, drug liver damage). Treatment of patients with diffuse liver diseases includes lifestyle and nutritional modification, the use of hepatoprotective drugs, and means of correcting the intestinal barrier (bibliography: 30 refs).
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Abdelrahman MM, Abdel-baset AA, Younis MA, Mahmoud MG, Shafik NS. Liver function test abnormalities in COVID-19 patients and factors affecting them - a retrospective study. Clin Exp Hepatol 2021; 7:297-304. [PMID: 34712832 PMCID: PMC8527347 DOI: 10.5114/ceh.2021.109225] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Accepted: 05/24/2021] [Indexed: 12/15/2022] Open
Abstract
AIM OF THE STUDY We aimed to study liver function test abnormalities in our COVID-19 patients and factors affecting them and to evaluate whether liver function test abnormalities are related to the severity of COVID-19. MATERIAL AND METHODS Our retrospective study included 118 patients who were SARS-CoV-2 positive. Their median age was 40 years. Fifty percent were male. Clinical and biochemical data were collected from patient records during the period from the start of June 2020 to the end of July 2020. Liver function test abnormalities included: alanine aminotransferase (ALT) > 40 U/l, aspartate aminotransferase (AST) > 40 U/l, serum albumin < 3.5 mg/dl, total bilirubin > 1.2 mg/dl, and international normalized ratio (INR) > 1.2. RESULTS Forty-four percent of COVID-19 patients had liver function test (LFT) abnormalities. In patients with severe SARS-CoV-2, AST, total bilirubin and INR levels were significantly higher than in patients with the non-severe disease. Levels of hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum ferritin, D-dimer, and serum glucose were significantly higher in SARS-CoV-2 patients with LFT abnormalities than those with normal liver function. CONCLUSIONS LFT abnormalities are very common in SARS-CoV2 positive patients, especially those with the severe form. Levels of ESR, CRP, serum ferritin, and D-dimer were higher in COVID-19 patients with LFT abnormalities than those with normal LFT. High serum ferritin levels might be potential risk factors for LFT abnormalities.
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Affiliation(s)
| | | | - Mustafa Adel Younis
- Clinical and Chemical Pathology Department, Faculty of Medicine, Sohag University, Egypt
| | | | - Noha Saber Shafik
- Medical Microbiology and Immunology Department, Faculty of Medicine, Sohag University, Egypt
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Gracia-Ramos AE, Jaquez-Quintana JO, Contreras-Omaña R, Auron M. Liver dysfunction and SARS-CoV-2 infection. World J Gastroenterol 2021; 27:3951-3970. [PMID: 34326607 PMCID: PMC8311530 DOI: 10.3748/wjg.v27.i26.3951] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/09/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 infection is the cause of coronavirus disease 2019 (COVID-19), which predominantly affects the respiratory system; it also causes systemic and multi-organic disease. Liver damage is among the main extrapulmonary manifestations. COVID-19-associated liver injury is defined as any liver damage occurring during the disease course and treatment of COVID-19 in patients with or without pre-existing liver disease, and occurs in approximately one in five patients. Abnormal liver test results have been associated with a more severe course of COVID-19 and other complications, including death. Mechanisms linking COVID-19 to liver injury are diverse. Particular consideration should be made for patients with pre-existing liver disease, such as metabolic dysfunction-associated fatty liver disease, chronic liver disease due to viral or autoimmune disease, liver transplant carriers, or cirrhosis, given the risk for more severe outcomes. This manuscript summarizes the current lines of evidence on COVID-19-associated liver injury regarding pathophysiology, clinical significance, and management in both patients with or without pre-existing liver disease, to facilitate clinicians' access to updated information and patient care. Finally, we mention the ideas and recommendations to be considered for future research.
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Affiliation(s)
- Abraham Edgar Gracia-Ramos
- Department of Internal Medicine, General Hospital, National Medical Center "La Raza", Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico
| | - Joel Omar Jaquez-Quintana
- Gastroenterology Service and Department of Internal Medicine, Faculty of Medicine, University Hospital "Dr. José E. González”, Universidad Autónoma de Nuevo León, Monterrey 64460, Mexico
| | - Raúl Contreras-Omaña
- Centro de Estudio e Investigación en Enfermedades Hepáticas y Toxicológicas (CEIHET), Pachuca 42184, Mexico
| | - Moises Auron
- Departments of Hospital Medicine and Pediatric Hospital Medicine, Cleveland Clinic, Cleveland, OH 44195, United States
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Srivastava S, Garg I. Post COVID-19 infection: Long-term effects on liver and kidneys. World J Meta-Anal 2021; 9:220-233. [DOI: 10.13105/wjma.v9.i3.220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 05/07/2021] [Accepted: 06/04/2021] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 is a pandemic, which has affected millions of people across the globe in the year 2020. This disease is caused by a virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that belongs to the family of coronaviruses and primarily affects the respiratory system. This infection has a wide spectrum of clinical manifestations ranging from asymptomatic form to mild, moderate and severe forms depending upon the age, comorbidity and immunity of an affected individual. Hyper-inflammatory response due to SARS-CoV-2 adversely affect several internal organs. Besides lung injury, which is the main outcome of SARS-CoV-2 infection, it has been reported to adversely impact other organs including the liver and kidneys. SARS-CoV-2 virus can also have a direct adverse impact on liver as well as kidneys due to systemic inflammatory response or drug toxicity, leading to elevated levels of liver injury markers and acute kidney injury. Clinical outcomes of SARS-CoV-2 infection could be worse in patients suffering from pre-existing liver and kidney disease. So far, there have been several reports on the mechanism of liver and kidney injury during SARS-CoV-2 viral attack. However, the long-term impact of this infection on these organs is yet to be understood. This review summarizes the possible causes and effects of SARS-CoV-2 on the liver and kidneys during the infection and post recovery based on available literature.
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Affiliation(s)
- Swati Srivastava
- Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization, New Delhi 110054, Indiana, India
| | - Iti Garg
- Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization, New Delhi 110054, Indiana, India
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Alventosa Mateu C, Urquijo Ponce JJ, Puchades Gimeno F, Benlloch Pérez S, Sanz Herrero F, Latorre Sánchez M, García Deltoro M, Gimeno Cardona C, Ocete Mochón MD, Diago Madrid M. Abnormal liver biochemistry constitutes an independent prognostic factor of a less favorable clinical course in patients with COVID-19. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2021; 113:825-832. [PMID: 34157846 DOI: 10.17235/reed.2021.7842/2021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
INTRODUCTION Abnormal liver biochemistry (ALB) is correlated with increased clinical involvement or severity in COVID-19, but its prognostic implications have not been studied extensively. Our aim is to determine whether ALB is a risk factor for an unfavorable clinical outcome and involvement. MATERIALS AND METHODS Retrospective, single-center study of confirmed COVID-19 cases. Patients with pharmacological hepatotoxicity or liver diseases were excluded. ALB was defined as the elevation of total bilirubin, AST, ALT, alkaline phosphatase and/or GGT above the upper limit of normal. An assessment was first made of the correlation between ALB and the need for hospitalization. This was followed by an assessment of the correlation of hospitalized patients with demographic variables, comorbidities and treatment for COVID-19 and with clinical involvement and outcome. Statistical analysis was performed using age-adjusted multiple logistic regression with a p-value of <0.05 RESULTS: Of 1,277 confirmed cases, 346 required hospitalization, and 302 were included. The prevalence of ALB was higher in hospitalized patients compared to non-hospitalized patients (60.9% vs. 10.3%, p ˂0.001). Among the hospitalized patients, there was no correlation between ALB and demographic variables, comorbidities or treatment for COVID-19, except for low molecular weight heparin. We found a significant correlation between ALB and moderate/severe COVID-19 involvement and between unfavorable clinical outcomes and elevated total bilirubin. The period of greatest clinical worsening and deterioration of liver biochemistry parameters occurred during the first seven days. There was a significant correlation between ALB and a longer hospital stay and admission to the Intensive Care Unit, but this did not imply higher mortality. CONCLUSIONS ALB is correlated with greater clinical involvement and worse clinical outcomes in hospitalized patients with COVID-19.
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Bende F, Tudoran C, Sporea I, Fofiu R, Bâldea V, Cotrău R, Popescu A, Sirli R, Ungureanu BS, Tudoran M. A Multidisciplinary Approach to Evaluate the Presence of Hepatic and Cardiac Abnormalities in Patients with Post-Acute COVID-19 Syndrome-A Pilot Study. J Clin Med 2021; 10:2507. [PMID: 34204032 PMCID: PMC8201250 DOI: 10.3390/jcm10112507] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 06/02/2021] [Accepted: 06/04/2021] [Indexed: 02/06/2023] Open
Abstract
(1) Background: Patients suffering from the novel coronavirus 2019 (COVID-19) disease could experience several extra-pulmonary involvements, including cardiovascular complications and liver injury. This study aims to evaluate the presence of cardiac and liver alterations in patients with post-acute COVID-19 syndrome using transthoracic echocardiography (TTE) and liver elastography (LE). (2) Methods: A total of 97 subjects recovering from COVID-19, attending the hospital's specialized outpatient clinic for persisting symptoms at 3 to 11 weeks after the acute illness, were included in this study. They all had a basal COVID-19 assessment, and subsequently, a clinical evaluation, laboratory tests, TTE, and LE. (3) Results: considering the presence of pulmonary injury during COVID-19, patients were divided into two groups. Although none of them had altered systolic function, we evidenced pulmonary hypertension, diastolic dysfunction, increased liver stiffness, viscosity, and steatosis in around one-third of the patients, with significantly higher values in subjects with pulmonary injury compared to those without. (4) Conclusion: persisting symptoms characterizing the post-acute COVID-19 syndrome could be explained by residual cardiac and hepatic lesions, which were worse in more severe COVID-19 forms. These patients may be at risk of developing liver fibrosis and cardiac alterations and should be investigated in the first 12 weeks after the onset of the infection.
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Affiliation(s)
- Felix Bende
- Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy “Victor Babes” Timisoara, 300041 Timisoara, Romania; (F.B.); (I.S.); (R.F.); (V.B.); (R.C.); (A.P.); (R.S.)
- Center of Advanced Research in Gastroenterology and Hepatology, Faculty of Medicine, University of Medicine and Pharmacy “Victor Babes” Timisoara, 300041 Timisoara, Romania
- County Emergency Hospital “Pius Brinzeu”, L. Rebreanu, Nr. 156, 300723 Timisoara, Romania;
| | - Cristina Tudoran
- County Emergency Hospital “Pius Brinzeu”, L. Rebreanu, Nr. 156, 300723 Timisoara, Romania;
- Center of Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, University of Medicine and Pharmacy “Victor Babes” Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania
- Department VII, Internal Medicine II, Discipline of Cardiology, University of Medicine and Pharmacy “Victor Babes” Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania
| | - Ioan Sporea
- Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy “Victor Babes” Timisoara, 300041 Timisoara, Romania; (F.B.); (I.S.); (R.F.); (V.B.); (R.C.); (A.P.); (R.S.)
- Center of Advanced Research in Gastroenterology and Hepatology, Faculty of Medicine, University of Medicine and Pharmacy “Victor Babes” Timisoara, 300041 Timisoara, Romania
- County Emergency Hospital “Pius Brinzeu”, L. Rebreanu, Nr. 156, 300723 Timisoara, Romania;
| | - Renata Fofiu
- Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy “Victor Babes” Timisoara, 300041 Timisoara, Romania; (F.B.); (I.S.); (R.F.); (V.B.); (R.C.); (A.P.); (R.S.)
- Center of Advanced Research in Gastroenterology and Hepatology, Faculty of Medicine, University of Medicine and Pharmacy “Victor Babes” Timisoara, 300041 Timisoara, Romania
| | - Victor Bâldea
- Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy “Victor Babes” Timisoara, 300041 Timisoara, Romania; (F.B.); (I.S.); (R.F.); (V.B.); (R.C.); (A.P.); (R.S.)
- Center of Advanced Research in Gastroenterology and Hepatology, Faculty of Medicine, University of Medicine and Pharmacy “Victor Babes” Timisoara, 300041 Timisoara, Romania
| | - Radu Cotrău
- Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy “Victor Babes” Timisoara, 300041 Timisoara, Romania; (F.B.); (I.S.); (R.F.); (V.B.); (R.C.); (A.P.); (R.S.)
- Center of Advanced Research in Gastroenterology and Hepatology, Faculty of Medicine, University of Medicine and Pharmacy “Victor Babes” Timisoara, 300041 Timisoara, Romania
| | - Alina Popescu
- Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy “Victor Babes” Timisoara, 300041 Timisoara, Romania; (F.B.); (I.S.); (R.F.); (V.B.); (R.C.); (A.P.); (R.S.)
- Center of Advanced Research in Gastroenterology and Hepatology, Faculty of Medicine, University of Medicine and Pharmacy “Victor Babes” Timisoara, 300041 Timisoara, Romania
- County Emergency Hospital “Pius Brinzeu”, L. Rebreanu, Nr. 156, 300723 Timisoara, Romania;
| | - Roxana Sirli
- Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy “Victor Babes” Timisoara, 300041 Timisoara, Romania; (F.B.); (I.S.); (R.F.); (V.B.); (R.C.); (A.P.); (R.S.)
- Center of Advanced Research in Gastroenterology and Hepatology, Faculty of Medicine, University of Medicine and Pharmacy “Victor Babes” Timisoara, 300041 Timisoara, Romania
- County Emergency Hospital “Pius Brinzeu”, L. Rebreanu, Nr. 156, 300723 Timisoara, Romania;
| | - Bogdan Silviu Ungureanu
- Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Mariana Tudoran
- County Emergency Hospital “Pius Brinzeu”, L. Rebreanu, Nr. 156, 300723 Timisoara, Romania;
- Center of Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, University of Medicine and Pharmacy “Victor Babes” Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania
- Department VII, Internal Medicine II, Discipline of Cardiology, University of Medicine and Pharmacy “Victor Babes” Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania
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Leowattana W. Angiotensin-converting enzyme 2 receptors, chronic liver diseases, common medications, and clinical outcomes in coronavirus disease 2019 patients. World J Virol 2021; 10:86-96. [PMID: 34079691 PMCID: PMC8152453 DOI: 10.5501/wjv.v10.i3.86] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 03/10/2021] [Accepted: 04/26/2021] [Indexed: 02/06/2023] Open
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), enters affected cells through the angiotensin-converting enzyme 2 (ACE2) receptor, which is highly expressed in type II alveolar cells, enterocytes, and cholangiocytes. SARS-CoV-2 infection causes fever, dry cough, and breathing difficulty, which can progress to respiratory distress due to interstitial pneumonia, and hepatobiliary injury due to COVID-19 is increasingly recognized. The hepatobiliary injury may be evident at presentation of the disease or develop during the disease progression. The development of more severe clinical outcomes in patients with chronic liver diseases (CLD) with or without cirrhosis infected with SARS-CoV-2 has not been elucidated. Moreover, there is limited data related to common medications that affect the disease severity of COVID-19 patients. Additionally, ACE2 receptor expression of hepatobiliary tissue related to the disease severity also have not been clarified. This review summarized the current situation regarding the clinical outcomes of COVID-19 patients with chronic liver diseases who were treated with common medications. Furthermore, the association between ACE2 receptor expression and disease severity in these patients is discussed.
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Affiliation(s)
- Wattana Leowattana
- Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
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Grinevich VB, Kravchuk YA, Ped VI, Sas EI, Salikova SP, Gubonina IV, Tkachenko EI, Sitkin SI, Lazebnik LB, Golovanova EV, Belousova EA, Makarchuk PA, Eremina EY, Sarsenbaeva AS, Abdulganieva DI, Tarasova LV, Gromova OA, Ratnikov VA, Kozlov KV, Ratnikova AK. Management of patients with digestive diseases during the COVID-19 pandemic. Clinical Practice Guidelines by the Russian scientific medical society of internal medicine (RSMSIM) and the Gastroenterological Scientific Society of Russia (2nd edition). EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2021:5-82. [DOI: 10.31146/1682-8658-ecg-187-3-5-82] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/26/2023]
Abstract
The presented clinical practice guidelines of the Gastroenterological Scientific Society of Russia (GSSR), diagnostic, and therapeutic approaches for patients with digestive diseases during the COVID-19 pandemic. The guidelines were approved by the XXIII Congress of the GSSR and the 22nd International Slavonic-Baltic Scientifi c Forum “St. Petersburg - Gastro-2020 ON-LINE” (St. Petersburg, June 11, 2020). The presented clinical practice guidelines of the Russian Scientific Medical Society of Internal Medicine (RSMSIM) and the Gastroenterological Scientific Society of Russia (GSSR), diagnostic, and therapeutic approaches for patients with digestive diseases during the COVID-19 pandemic. The recommendations were approved at the XV National Congress of Internal Medicine, XXIII Congress of NOGR on the basis of the 1st edition, adopted at the 22nd International Slavic- Baltic Scientific Forum “St. Petersburg - Gastro-2020 ON-LINE”.
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Affiliation(s)
| | | | - V. I. Ped
- Military Medical Academy named after S. M. Kirov
| | - E. I. Sas
- Military Medical Academy named after S. M. Kirov
| | | | | | | | - S. I. Sitkin
- State Research Institute of Highly Pure Biopreparations of FMBA of Russia; Almazov National Medical Research Centre; North-Western state medical University named after I. I. Mechnikov, Ministry of health of the Russian Federation
| | - L. B. Lazebnik
- Moscow state University of Medicine a. Densitry named after A. I. Yevdokimov of the Ministry of Health of Russia
| | - E. V. Golovanova
- Moscow state University of Medicine a. Densitry named after A. I. Yevdokimov of the Ministry of Health of Russia
| | - E. A. Belousova
- State Budgetary Institution of Moscow Region “Moscow Regional Research Clinical Institute n.a. M. F. Vladimirsky”
| | - P. A. Makarchuk
- State Budgetary Institution of Moscow Region “Moscow Regional Research Clinical Institute n.a. M. F. Vladimirsky”
| | - E. Yu. Eremina
- Federal State Budgetary Educational Institution of Higher Education “National Research Ogarev Mordovia State University”
| | - A. S. Sarsenbaeva
- FSBEI HE SUSMU MOH Russia, st. Vorovskogo, 64, Ural Federal District
| | | | - L. V. Tarasova
- FSBEI of HE “The Chuvash State University n.a. I. N. Ulyanov”; BI of HE “The Surgut State University”
| | - O. A. Gromova
- Federal Research Center “Informatics and Management” of the Russian Academy of Sciences; Federal State Educational Institution of Higher Education Lomonosov Moscow State University
| | - V. A. Ratnikov
- Federal state budgetary institution “North-West District Scientific and Clinical Center named after L. G. Sokolov Federal Medical and Biological Agency“
| | - K. V. Kozlov
- Military Medical Academy named after S. M. Kirov
| | - A. K. Ratnikova
- Military Medical Academy named after S. M. Kirov; Federal state budgetary institution “North-West District Scientific and Clinical Center named after L. G. Sokolov Federal Medical and Biological Agency“
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Ahmad A, Ishtiaq SM, Khan JA, Aslam R, Ali S, Arshad MI. COVID-19 and comorbidities of hepatic diseases in a global perspective. World J Gastroenterol 2021; 27:1296-1310. [PMID: 33833483 PMCID: PMC8015303 DOI: 10.3748/wjg.v27.i13.1296] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 02/17/2021] [Accepted: 03/19/2021] [Indexed: 02/06/2023] Open
Abstract
The worldwide outbreak of coronavirus disease 2019 (COVID-19) has challenged the priorities of healthcare system in terms of different clinical management and infection transmission, particularly those related to hepatic-disease comorbidities. Epidemiological data evidenced that COVID-19 patients with altered liver function because of hepatitis infection and cholestasis have an adverse prognosis and experience worse health outcomes. COVID-19-associated liver injury is correlated with various liver diseases following a severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) infection that can progress during the treatment of COVID-19 patients with or without pre-existing liver disease. SARS-CoV-2 can induce liver injury in a number of ways including direct cytopathic effect of the virus on cholangiocytes/hepatocytes, immune-mediated damage, hypoxia, and sepsis. Indeed, immediate cytopathogenic effects of SARS-CoV-2 via its potential target, the angiotensin-converting enzyme-2 receptor, which is highly expressed in hepatocytes and cholangiocytes, renders the liver as an extra-respiratory organ with increased susceptibility to pathological outcomes. But, underlying COVID-19-linked liver disease pathogenesis with abnormal liver function tests (LFTs) is incompletely understood. Hence, we collated COVID-19-associated liver injuries with increased LFTs at the nexus of pre-existing liver diseases and COVID-19, and defining a plausible pathophysiological triad of COVID-19, hepatocellular damage, and liver disease. This review summarizes recent findings of the exacerbating role of COVID-19 in pre-existing liver disease and vice versa as well as international guidelines of clinical care, management, and treatment recommendations for COVID-19 patients with liver disease.
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Affiliation(s)
- Aqsa Ahmad
- Institute of Microbiology, University of Agriculture Faisalabad, Faisalabad 38040, Punjab, Pakistan
| | - Syeda Momna Ishtiaq
- Institute of Physiology and Pharmacology, University of Agriculture Faisalabad, Faisalabad 38040, Punjab, Pakistan
| | - Junaid Ali Khan
- Institute of Physiology and Pharmacology, University of Agriculture Faisalabad, Faisalabad 38040, Punjab, Pakistan
| | - Rizwan Aslam
- Institute of Microbiology, University of Agriculture Faisalabad, Faisalabad 38040, Punjab, Pakistan
| | - Sultan Ali
- Institute of Microbiology, University of Agriculture Faisalabad, Faisalabad 38040, Punjab, Pakistan
| | - Muhammad Imran Arshad
- Institute of Microbiology, University of Agriculture Faisalabad, Faisalabad 38040, Punjab, Pakistan
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Cichoż-Lach H, Michalak A. Liver injury in the era of COVID-19. World J Gastroenterol 2021; 27:377-390. [PMID: 33584070 PMCID: PMC7856845 DOI: 10.3748/wjg.v27.i5.377] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 12/25/2020] [Accepted: 01/08/2021] [Indexed: 02/06/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has undoubtedly revolutionized the whole globe and given a new point of view on respiratory tract infections. Nevertheless, coronavirus disease 2019 (COVID-19) cannot be perceived as a disease limited only to pneumonia with diverse severity. More and more reports have demonstrated a wide range of possible systemic symptoms, including hepatic complications. Liver injury has been observed in a significant proportion of patients, especially in those with a severe or critical illness. COVID-19 might provoke a deterioration of liver function in patients with already diagnosed chronic liver diseases and without pre-existing liver disorders. The deterioration of liver function worsens the prognosis, increases the risk of a severe course of SARS-CoV-2 infection and prolongs the hospital stay. In general, patients who develop liver dysfunction in COVID-19 are mainly males, elderly people, and those with higher body mass index. The underlying mechanisms for hepatic failure in patients infected with SARS-CoV-2 are still unclear, nevertheless liver damage appears to be directly connected with virus-induced cytopathic effects. A liver injury observed during hospitalization might be simultaneously caused by the use of potentially hepatotoxic drugs, mainly antiviral agents. This minireview focuses on a possible relationship between COVID-19 and the liver, potential molecular mechanisms of liver damage, the characteristics of liver injury and suggested factors predisposing to hepatic manifestations in COVID-19 patients.
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Affiliation(s)
- Halina Cichoż-Lach
- Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, Jaczewskiego 8, Lublin 20-954, Poland
| | - Agata Michalak
- Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, Jaczewskiego 8, Lublin 20-954, Poland
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Ng A. Graft injury and re-transplantation in liver transplant patients with COVID-19. JOURNAL OF LIVER TRANSPLANTATION 2021; 1:100008. [PMID: 38620664 PMCID: PMC8062408 DOI: 10.1016/j.liver.2021.100008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 04/14/2021] [Accepted: 04/17/2021] [Indexed: 11/24/2022] Open
Abstract
This article discusses the current scene of liver transplantation (LT) in light of the impact of COVID-19, with particular emphasis on the possibility of graft injury and re-transplantation in LT patients infected with SARS-CoV-2. A major concern is whether such patients experience a more severe form of disease which may lead to a higher risk of acute, irreversible liver injury. If this is serious, it may necessitate re-transplantation. This article aims to raise awareness in this relatively under-researched domain. More studies are required to evaluate this issue since it has strong implications in healthcare resource allocation and clinical decision-making. Several potential research directions are proposed, including the possibility of prolonging bridging therapy for non-urgent LT cases: patients with hepatocellular carcinoma; and whether hepatoprotective agents play a role in liver-sparing during SARS-CoV-2 infection. There is also substantial discussion of the relevance of lung injury in LT patients with COVID-19 since it is not uncommon regarding the high expression of ACE2 receptors in the lungs, and that lung injury remains the major cause of death in patients with chronic liver disease.
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Key Words
- ALT, alanine transaminase
- AST, aspartate transaminase
- Abbreviations: ACE2, angiotensin-converting enzyme 2
- BCLC, Barcelona Clinic Liver Cancer Staging
- COVID-19
- COVID-19, coronavirus disease 2019
- DEB, drug-eluting beads
- ICU, intensive care unit
- JAK, Janus Kinus
- LT, liver transplant
- OR, odds ratio
- TACE, transarterial chemoembolization
- UDCA, Ursodeoxycholic acid
- US, United States
- chronic liver disease
- graft injury
- liver transplant
- re-transplantation
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Affiliation(s)
- Alexander Ng
- University College London, Gower Street, London, United Kingdom
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44
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Liu Y, Li M, Liu D, Luo JF, Li N, Zhang X, Tang XJ, Zhang X, Liu J, Wang J, Wang T, Zhou YZ, Luo WX, Liang ZA, Luo FM, Li WM, Wang G. Developing a multivariable risk prediction model to predict prolonged viral clearance in patients with COVID-19. J Infect 2020; 82:e20-e22. [PMID: 33387568 PMCID: PMC7773527 DOI: 10.1016/j.jinf.2020.12.026] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 12/27/2020] [Accepted: 12/28/2020] [Indexed: 02/05/2023]
Affiliation(s)
- Ying Liu
- Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China; Laboratory of Pulmonary Immunology and inflammation, Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu 610041, PR China; Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Min Li
- Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China; Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Kunming Medical University, Kunming 650032, PR China
| | - Dan Liu
- Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China
| | - Jian Fei Luo
- Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan 430022, Hubei, PR China
| | - Nian Li
- Department of Medical Affairs, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Xuan Zhang
- Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China
| | - Xiao Ju Tang
- Laboratory of Pulmonary Immunology and inflammation, Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu 610041, PR China
| | - Xin Zhang
- Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China; Laboratory of Pulmonary Immunology and inflammation, Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu 610041, PR China; Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Jia Liu
- Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China; Laboratory of Pulmonary Immunology and inflammation, Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu 610041, PR China
| | - Ji Wang
- Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China; Laboratory of Pulmonary Immunology and inflammation, Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu 610041, PR China
| | - Ting Wang
- Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China; Laboratory of Pulmonary Immunology and inflammation, Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu 610041, PR China
| | - Yong Zao Zhou
- Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China; Laboratory of Pulmonary Immunology and inflammation, Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu 610041, PR China
| | - Wen Xin Luo
- Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China; Laboratory of Pulmonary Immunology and inflammation, Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu 610041, PR China
| | - Zong An Liang
- Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
| | - Feng Ming Luo
- Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China; Laboratory of Pulmonary Immunology and inflammation, Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu 610041, PR China.
| | - Wei Min Li
- Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
| | - Gang Wang
- Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China; Laboratory of Pulmonary Immunology and inflammation, Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu 610041, PR China.
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45
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Fierro NA. COVID-19 and the liver: What do we know after six months of the pandemic? Ann Hepatol 2020; 19:590-591. [PMID: 32956871 PMCID: PMC7500273 DOI: 10.1016/j.aohep.2020.09.001] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 09/02/2020] [Indexed: 02/07/2023]
Abstract
Despite liver injury in patients infected with severe acute respiratory syndrome (SARS) coronavirus (CoV)-2 (SARS-CoV-2) is associated with prolonged hospitalization, and liver dysfunction is mainly described in patients with severe viral disease. How liver abnormalities may affect virus infection is still unknown. Improved understanding of host genetics, lifestyle, underlying comorbidities and adequate follow-up of patients with liver damage are critical in the new scenario of the pandemic virus.
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Affiliation(s)
- Nora A. Fierro
- Correspondence to: Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, CP 045210, Ciudad de México México
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