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Pozzobon FM, Luiz RR, Parente JG, Guarilha TM, Fontes MPRC, Chindamo MC, de Mello Perez R. Combination of fibrosis-4 score and D-dimer: a practical approach to identify poor outcome in COVID-19. Eur J Gastroenterol Hepatol 2025:00042737-990000000-00503. [PMID: 40207484 DOI: 10.1097/meg.0000000000002966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/11/2025]
Abstract
AIM Fibrosis-4 (FIB-4) score and D-dimer (DD) have emerged as prognostic markers in coronavirus disease 2019 (COVID-19). However, precise cutoff points remain undefined, and their combined use has been scarcely studied. We aimed to analyze FIB-4 and DD performance, individually and combined, to predict outcomes among COVID-19 patients. METHODS From March to December 2020, hospitalized COVID-19 patients were evaluated based on clinical and laboratory tests from their first day of hospitalization. Primary outcome was inhospital mortality, and secondary outcomes included hospital stay length, ICU admission and duration, need for hemodialysis, ventilatory support, and extent of lung involvement. Optimal FIB-4 and DD cutoff points to predict mortality were established to maximize sensitivity and specificity. A sequential diagnostic strategy using both markers was subsequently evaluated. RESULTS Among 518 patients (61 ± 16 years, 64% men), the inhospital mortality rate was 18%. FIB-4 outperformed DD in predicting mortality (area under the receiver operating characteristic curve: 0.76 vs. 0.65, P = 0.003) and was chosen as the first step in sequential analysis. Mortality was higher in patients with FIB-4 ≥1.76 vs. FIB-4 <1.76 (26 vs. 5%, P < 0.001) and DD ≥2000 ng/ml vs. DD <2000 ng/ml (38 vs. 16%, P < 0.001). Using FIB-4 as a screening test (cutoff = 1.76, 90% sensitivity) followed by DD (cutoff = 2000 ng/ml; 90% specificity) identified a subgroup with higher mortality when compared with FIB-4 alone (48 vs. 26%, P < 0.001), missing the identification of only 2% of deaths. CONCLUSION Sequential use of FIB-4 and DD represents a comprehensive strategy to identify high-risk COVID-19 patients at hospital admission, potentially minimizing unnecessary DD tests in those deemed low-risk by FIB-4.
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Affiliation(s)
- Fernanda Manhães Pozzobon
- Department of Internal Medicine, Barra D'Or Hospital, Rede D'Or São Luiz, Rio de Janeiro
- Health Assistance Division, Fluminense Federal University (UFF), Niterói
| | - Ronir Raggio Luiz
- D'Or Institute for Research and Education (IDOR)
- Institute for Collective Health Studies, Federal University of Rio de Janeiro (UFRJ)
| | - Júlia Gomes Parente
- Department of Internal Medicine, Barra D'Or Hospital, Rede D'Or São Luiz, Rio de Janeiro
| | - Taísa Melo Guarilha
- Department of Internal Medicine, Barra D'Or Hospital, Rede D'Or São Luiz, Rio de Janeiro
| | | | - Maria Chiara Chindamo
- Department of Internal Medicine, Barra D'Or Hospital, Rede D'Or São Luiz, Rio de Janeiro
- Department of Internal Medicine, Medical School, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Renata de Mello Perez
- D'Or Institute for Research and Education (IDOR)
- Department of Internal Medicine, Medical School, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
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Yang Y, Jiang J, Zhou J, Wang S, Chen G, Zheng S. Clinical Course and Outcome of COVID-19 in Children With Biliary Atresia: A Retrospective Study. Health Sci Rep 2025; 8:e70462. [PMID: 39931263 PMCID: PMC11808391 DOI: 10.1002/hsr2.70462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 12/21/2024] [Accepted: 01/16/2025] [Indexed: 02/13/2025] Open
Abstract
Background and Aims To investigate the infection status and outcomes of biliary atresia (BA) patients during the coronavirus disease 2019 (COVID-19) pandemic in Chinese population. Methods This retrospective study involved Kasai-postoperative BA patients who had achieved jaundice-free during the SARS-CoV-2 outbreak from December 1, 2022 to February 28, 2023. Children without hepatobiliary diseases hospitalized during the same period were as control group. Data collected included nutritional status, comorbidities, epidemiologic characteristics, fever symptoms (duration, max), respiratory symptoms (cough, runny nose and shortness of breath), and gastrointestinal symptoms (diarrhea and vomiting). All cases infected with SARS-CoV-2 were followed up for 3 months. Results A total of 128 BA patients were enrolled, ranged in age from 6 months to 12 years old (median age: 1.8 years). A total of 51 (39.8%) and 49 BA patients (38.3%) were classified as confirmed and suspected COVID-19 cases, respectively. Only two confirmed cases presented with moderate symptoms, while the rest developed asymptomatic or mild cases. Compared to the 115 control groups, the proportion of symptomatic cases in BA was slightly higher (78.1% vs. 67.8%) without significant difference (p = 0.07). Similarly, no differences were found in proportion of fever, respiratory tract symptoms and gastrointestinal symptoms between BA and control groups. However, it is worth noting that 7 BA patients developed symptoms of cholangitis during SARS-CoV-2 infection, who experienced pale stool and elevated bilirubin levels. After hospitalization, six patients achieved jaundice-free survival, but one child finally had to undergo liver transplantation due to hepatic failure. Conclusions The symptoms and course of COVID-19 in BA patients were similar to those in healthy population. The vast majority of BA patients made a good recovery from COVID-19.
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Affiliation(s)
- Yifan Yang
- Department of Pediatric SurgeryChildren's Hospital of Fudan University, and Key Laboratory of Neonatal Disease, Ministry of HealthShanghaiChina
| | - Jingying Jiang
- Department of Pediatric SurgeryChildren's Hospital of Fudan University, and Key Laboratory of Neonatal Disease, Ministry of HealthShanghaiChina
| | - Jin Zhou
- Department of Pediatric SurgeryChildren's Hospital of Fudan University, and Key Laboratory of Neonatal Disease, Ministry of HealthShanghaiChina
| | - Shuxin Wang
- Department of Pediatric SurgeryChildren's Hospital of Fudan University, and Key Laboratory of Neonatal Disease, Ministry of HealthShanghaiChina
| | - Gong Chen
- Department of Pediatric SurgeryChildren's Hospital of Fudan University, and Key Laboratory of Neonatal Disease, Ministry of HealthShanghaiChina
| | - Shan Zheng
- Department of Pediatric SurgeryChildren's Hospital of Fudan University, and Key Laboratory of Neonatal Disease, Ministry of HealthShanghaiChina
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Wu H, Zhang Y, Tang W, Lv M, Chen Z, Meng F, Zhao Y, Xu H, Dai Y, Xue J, Wang J, Dong L, Wu D, Zhang S, Xue R. Liver function abnormality on admission predicts long COVID syndrome in digestive system. Heliyon 2024; 10:e37664. [PMID: 39386803 PMCID: PMC11462002 DOI: 10.1016/j.heliyon.2024.e37664] [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: 03/30/2024] [Revised: 08/06/2024] [Accepted: 09/07/2024] [Indexed: 10/12/2024] Open
Abstract
BACKGROUND Clinical practice showed that many patients with SARS-CoV-2 infection presented with long COVID syndrome in digestive system. We sought to investigate the factor affecting the incidence of long COVID syndrome in digestive system. METHODS AND RESULTS Patients with SARS-CoV-2 infection diagnosed at two centers of Zhongshan Hospital and one center of Shanghai Pudong Hospital from March 01, 2022 to May 31, 2022 were enrolled, collected in the hospital database, and followed up until March 30, 2023. The primary outcome of the study was the occurrence of post-acute sequelae of COVID-19 in the digestive system (long COVID syndrome). Modified Poisson regression was used to calculate the relative risk (RR). This cohort study included 494 patients with SARS-CoV-2 infection, 144 (29.1 %) patients developed liver function abnormality on admission. During the follow-up period, the primary study outcome occurred in 30 (20.8 %) of the group presenting with liver function abnormality on admission and in 20 (5.7 %) of the group without liver function abnormality on admission (adjusted, RR = 3.550, 95%CI: 2.099-6.006, P ≤ 0.001). CONCLUSION Our study suggests that patients with COVID-19 who experience liver function abnormality on admission have an increased risk of developing long COVID syndrome in the digestive system.
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Affiliation(s)
- Huibin Wu
- Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Yunjie Zhang
- Department of Clinical Medicine, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Wenqing Tang
- Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Minzhi Lv
- Department of Biostatistics, Clinical Research Unit, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Department of Biostatistics, Clinical Research Unit, Key Laboratory of Public Health Safety of Ministry of Education, Key Laboratory for Health Technology Assessment, National Commission of Health, School of Public Health, Center of Evidence-Based Medicine, Fudan University, Shanghai, 200032, China
| | - Zhixue Chen
- Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Fansheng Meng
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Yitong Zhao
- School of Medicine, Anhui University of Science and Technology, Anhui, 232000, China
| | - Huajie Xu
- Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, National Clinical Research Center for Interventional Medicine, Fudan University, Shanghai, 200032, China
| | - Yuxin Dai
- NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China
| | - Jindan Xue
- School of Medicine, Anhui University of Science and Technology, Anhui, 232000, China
| | - Jingya Wang
- Department of Biochemistry and Molecular Biology, Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China
| | - Ling Dong
- Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Dejun Wu
- Department of Gastrointestinal Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China
| | - Si Zhang
- NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China
| | - Ruyi Xue
- Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Shanghai Baoshan District Wusong Central Hospital (Zhongshan Hospital Wusong Branch, Fudan University), Shanghai, 200940, China
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Lucena Valera A, Aller de la Fuente R, Sánchez Torrijos Y, Romero Gómez M, Ampuero Herrojo J. FIB-4 score as a predictor of COVID-19-related severity in hospitalized patients. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2024; 116:465-471. [PMID: 38767045 DOI: 10.17235/reed.2024.9811/2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/22/2024]
Abstract
AIM to determine the impact of liver fibrosis on the prognosis of COVID and liver injury associated with the infection. METHODS retrospective multicenter study including 575 patients requiring admission for COVID-19 between January and June 2020. Fibrosis index-4 (FIB-4) was calculated within six months prior to infection and at six months post-infection. RESULTS baseline FIB-4 was elevated in patients who died (1.91 ± 0.95 vs 1.43 ± 0.85; p < 0.001). In addition, 17.1 % (32/187) of patients with baseline FIB-4 < 1.45 died vs 52.9 % (9/17) with FIB-4 > 3.25 (p < 0.001). In the adjusted multivariate analysis, baseline FIB-4 (OR 1.61 [95 % CI: 1.19-2.18]; p = 0.002) was independently associated with mortality. Parameters associated with liver injury, including aspartate aminotransferase (AST) (28 ± 10 vs 45 ± 56 IU/l; p < 0.001) and alanine aminotransferase (ALT) (20 ± 12 vs 38 ± 48 IU/l; p < 0.001) were significantly higher at admission compared to baseline. Furthermore, FIB-4 increased from baseline to the time of admission (1.53 ± 0.88 vs 2.55 ± 1.91; p < 0.001), and up to 6.9 % (10/145) of patients with FIB-4 < 1.45 on admission died vs 47.5 % if FIB-4 > 3.25 (58/122) (p < 0.001). In the adjusted multivariate analysis, FIB-4 on admission (OR 1.14 [95 % CI: 1.03-1.27]; p = 0.015) was independently associated with mortality. In addition, AST (42 ± 38 vs 22 ± 17 IU/l; p < 0.001) and ALT (40 ± 50 vs 20 ± 19 IU/l; p < 0.001) were significantly reduced at six months after the resolution of infection. Accordingly, FIB-4 decreased significantly (2.12 ± 1.25 vs 1.32 ± 0.57; p < 0.001) six months after the infection. CONCLUSION increased FIB-4, either at baseline or at the time of admission, was associated with severity and mortality related to respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the liver damage expressed by elevated transaminases and FIB-4 levels was reversible in most of patients.
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Moeed A, Larik MO, Fahim MAA, Rahman HAU, Najmi L, Changez MIK, Javed MM, Hasibuzzaman MA. Impact of non-alcoholic fatty liver disease on coronavirus disease 2019: A systematic review. World J Hepatol 2024; 16:1185-1198. [PMID: 39221098 PMCID: PMC11362910 DOI: 10.4254/wjh.v16.i8.1185] [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: 06/19/2024] [Revised: 07/17/2024] [Accepted: 07/26/2024] [Indexed: 08/21/2024] Open
Abstract
BACKGROUND Many studies have revealed a link between non-alcoholic fatty liver disease (NAFLD) and coronavirus disease 2019 (COVID-19), making understanding the relationship between these two conditions an absolute requirement. AIM To provide a qualitative synthesis on the currently present data evaluating COVID-19 and NAFLD. METHODS This systematic review was conducted in accordance with the guidelines provided by preferred reporting items for systematic reviews and meta-analyses and the questionnaire utilized the population, intervention, comparison, and outcome framework. The search strategy was run on three separate databases, PubMed/MEDLINE, Scopus, and Cochrane Central, which were systematically searched from inception until March 2024 to select all relevant studies. In addition, ClinicalTrials.gov, Medrxiv.org, and Google Scholar were searched to identify grey literature. RESULTS After retrieval of 11 studies, a total of 39282 patients data were pooled. Mortality was found in 11.5% and 9.4% of people in NAFLD and non-NAFLD groups. In all, 23.2% of NAFLD patients and 22% of non-NAFLD admissions diagnosed with COVID-19 were admitted to the intensive care unit, with days of stay varying. Ventilatory support ranged from 5% to 40.5% in the NAFLD cohort and from 3.1% to 20% in the non-NAFLD cohort. The incidence of acute liver injury showed significance. Clinical improvement on days 7 and 14 between the two classifications was significant. Hospitalization stay ranged from 9.6 days to 18.8 days and 7.3 days to 16.4 days in the aforementioned cohorts respectively, with 73.3% and 76.3% of patients being discharged. Readmission rates varied. CONCLUSION Clinical outcomes except mortality consistently showed a worsening trend in patients with NAFLD and concomitant COVID-19. Further research in conducting prospective longitudinal studies is essential for a more powerful conclusion.
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Affiliation(s)
- Abdul Moeed
- Department of Internal Medicine, Dow University of Health Sciences, Karachi 74200, Sindh, Pakistan
| | - Muhammad Omar Larik
- Department of Internal Medicine, Dow International Medical College, Karachi 74200, Sindh, Pakistan
| | - Muhammad Ahmed Ali Fahim
- Department of Internal Medicine, Dow University of Health Sciences, Karachi 74200, Sindh, Pakistan
| | - Hafsah Alim Ur Rahman
- Department of Internal Medicine, Dow University of Health Sciences, Karachi 74200, Sindh, Pakistan
| | - Lubna Najmi
- Department of Internal Medicine, Ziauddin University, Karachi 75000, Sindh, Pakistan
| | - Mah I Kan Changez
- Department of Research, Yale University, New Haven 06520, CT, United States
| | - Muhammad Moiz Javed
- Department of Internal Medicine, King Edward Medical University, Lahore 54000, Punjab, Pakistan
| | - Md Al Hasibuzzaman
- Institute of Nutrition and Food Science, University of Dhaka, Dhaka 1000, Bangladesh
- Department of Medicine, The Affiliated Hospital of Medical School of Ningbo University, Ningbo 315211, Zhejiang Province, China.
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Akpoviroro O, Sauers NK, Uwandu Q, Castagne M, Akpoviroro OP, Humayun S, Mirza W, Woodard J. Severe COVID-19 infection: An institutional review and literature overview. PLoS One 2024; 19:e0304960. [PMID: 39163410 PMCID: PMC11335168 DOI: 10.1371/journal.pone.0304960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 05/21/2024] [Indexed: 08/22/2024] Open
Abstract
BACKGROUND Our study aimed to describe the group of severe COVID-19 patients at an institutional level, and determine factors associated with different outcomes. METHODS A retrospective chart review of patients admitted with severe acute hypoxic respiratory failure due to COVID-19 infection. Based on outcomes, we categorized 3 groups of severe COVID-19: (1) Favorable outcome: progressive care unit admission and discharge (2) Intermediate outcome: ICU care (3) Poor outcome: in-hospital mortality. RESULTS Eighty-nine patients met our inclusion criteria; 42.7% were female. The average age was 59.7 (standard deviation (SD):13.7). Most of the population were Caucasian (95.5%) and non-Hispanic (91.0%). Age, sex, race, and ethnicity were similar between outcome groups. Medicare and Medicaid patients accounted for 62.9%. The average BMI was 33.5 (SD:8.2). Moderate comorbidity was observed, with an average Charlson Comorbidity index (CCI) of 3.8 (SD:2.6). There were no differences in the average CCI between groups(p = 0.291). Many patients (67.4%) had hypertension, diabetes (42.7%) and chronic lung disease (32.6%). A statistical difference was found when chronic lung disease was evaluated; p = 0.002. The prevalence of chronic lung disease was 19.6%, 27.8%, and 40% in the favorable, intermediate, and poor outcome groups, respectively. Smoking history was associated with poor outcomes (p = 0.04). Only 7.9% were fully vaccinated. Almost half (46.1%) were intubated and mechanically ventilated. Patients spent an average of 12.1 days ventilated (SD:8.5), with an average of 6.0 days from admission to ventilation (SD:5.1). The intermediate group had a shorter average interval from admission to ventilator (77.2 hours, SD:67.6), than the poor group (212.8 hours, SD:126.8); (p = 0.001). The presence of bacterial pneumonia was greatest in the intermediate group (72.2%), compared to the favorable group (17.4%), and the poor group (56%); this was significant (p<0.0001). In-hospital mortality was seen in 28.1%. CONCLUSION Most patients were male, obese, had moderate-level comorbidity, a history of tobacco abuse, and government-funded insurance. Nearly 50% required mechanical ventilation, and about 28% died during hospitalization. Bacterial pneumonia was most prevalent in intubated groups. Patients who were intubated with a good outcome were intubated earlier during their hospital course, with an average difference of 135.6 hours. A history of cigarette smoking and chronic lung disease were associated with poor outcomes.
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Affiliation(s)
- Ogheneyoma Akpoviroro
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, Pennsylvania, United States of America
| | - Nathan Kyle Sauers
- Department of Engineering, Pennsylvania State University, State College, Pennsylvania, United States of America
| | - Queeneth Uwandu
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, Pennsylvania, United States of America
| | - Myriam Castagne
- Clinical & Translational Science Institute, Boston University, Boston, Massachusetts, United States of America
| | | | - Sara Humayun
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, Pennsylvania, United States of America
| | - Wasique Mirza
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, Pennsylvania, United States of America
| | - Jameson Woodard
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, Pennsylvania, United States of America
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Fischer AK, Stippel D, Canbay A, Nierhoff D, Thomas M, Best J, Büttner R, Drebber U. COVID-19-associated secondary sclerosing cholangitis with liver transplantation. Virchows Arch 2024; 485:371-377. [PMID: 38526652 PMCID: PMC11329547 DOI: 10.1007/s00428-024-03753-4] [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: 11/13/2023] [Revised: 01/22/2024] [Accepted: 01/27/2024] [Indexed: 03/27/2024]
Abstract
We report on two cases of orthotopic liver transplantation (OLTX) due to SARS-Cov2-associated secondary sclerosing cholangitis (SSC) following long-term artificial respiration and extra-corporal membrane oxygenation in intensive care. Under these conditions, SSC is a rapidly progredient biliary disease featuring degenerative cholangiopathy, loss of bile ducts, ductular and parenchymal cholestasis, biliary fibrosis, and finally cirrhosis. Reduced perfusion and oxygenation of the peribiliary plexus, severe concurrent infections, and secondary medico-toxic effects appear to play a crucial role in the pathogenesis of the disease. A direct cytopathic effect of SARS-Cov2 on endothelial cells followed by thrombosis and fibrosing obliteration in all parts of the vascular bed of the liver may enhance the virus-associated liver disease and particularly SSC.
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Affiliation(s)
- Anne Kristin Fischer
- Institute of Pathology, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
| | - Dirk Stippel
- Department of Surgery, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Ali Canbay
- Department of Internal Medicine, Transplant Medicine, Gastroenterology and Hepatology, University of Bochum, In Der Schornau 23-25 44892, Bochum, Germany
| | - Dirk Nierhoff
- Department of Internal Medicine, Gastroenterology and Hepatology, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Michael Thomas
- Department of Surgery, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Jan Best
- Department of Internal Medicine, Transplant Medicine, Gastroenterology and Hepatology, University of Bochum, In Der Schornau 23-25 44892, Bochum, Germany
| | - Reinhard Büttner
- Institute of Pathology, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Uta Drebber
- Institute of Pathology, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
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Baik SM, Hong KS, Lee JM, Park DJ. Integrating ensemble and machine learning models for early prediction of pneumonia mortality using laboratory tests. Heliyon 2024; 10:e34525. [PMID: 39149016 PMCID: PMC11324817 DOI: 10.1016/j.heliyon.2024.e34525] [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: 08/10/2023] [Revised: 07/09/2024] [Accepted: 07/10/2024] [Indexed: 08/17/2024] Open
Abstract
Background The recent use of artificial intelligence (AI) in medical research is noteworthy. However, most research has focused on medical imaging. Although the importance of laboratory tests in the clinical field is acknowledged by clinicians, they are undervalued in medical AI research. Our study aims to develop an early prediction AI model for pneumonia mortality, primarily using laboratory test results. Materials and methods We developed a mortality prediction model using initial laboratory results and basic clinical information of patients with pneumonia. Several machine learning (ML) models and a deep learning method-multilayer perceptron (MLP)-were selected for model development. The area under the receiver operating characteristic curve (AUROC) and F1-score were optimized to improve model performance. In addition, an ensemble model was developed by blending several models to improve the prediction performance. We used 80,940 data instances for model development. Results Among the ML models, XGBoost exhibited the best performance (AUROC = 0.8989, accuracy = 0.88, F1-score = 0.80). MLP achieved an AUROC of 0.8498, accuracy of 0.86, and F1-score of 0.75. The performance of the ensemble model was the best among the developed models, with an AUROC of 0.9006, accuracy of 0.90, and F1-score of 0.81. Several laboratory tests were conducted to identify risk factors that affect pneumonia mortality using the "Feature importance" technique and SHapley Additive exPlanations. We identified several laboratory results, including systolic blood pressure, serum glucose level, age, aspartate aminotransferase-to-alanine aminotransferase ratio, and monocyte-to-lymphocyte ratio, as significant predictors of mortality in patients with pneumonia. Conclusions Our study demonstrates that the ensemble model, incorporating XGBoost, CatBoost, and LGBM techniques, outperforms individual ML and deep learning models in predicting pneumonia mortality. Our findings emphasize the importance of integrating AI techniques to leverage laboratory test data effectively, offering a promising direction for advancing AI applications in medical research and clinical decision-making.
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Affiliation(s)
- Seung Min Baik
- Division of Critical Care Medicine, Department of Surgery, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, South Korea
| | - Kyung Sook Hong
- Division of Critical Care Medicine, Department of Surgery, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, Seoul, South Korea
| | - Jae-Myeong Lee
- Department of Acute Care Surgery, Korea University Anam Hospital, Seoul, South Korea
| | - Dong Jin Park
- Department of Laboratory Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
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da Silva CS, Martinelli KG, Viana MWM, Soares DDS, Corrêa YGS, da Silva LL, de Paula VS, Rodrigues LLS, Villar LM. Liver and Inflammatory Biomarkers Are Related to High Mortality in Hospitalized Patients with COVID-19 in Brazilian Amazon Region. Life (Basel) 2024; 14:869. [PMID: 39063622 PMCID: PMC11277996 DOI: 10.3390/life14070869] [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: 10/27/2023] [Revised: 12/01/2023] [Accepted: 12/08/2023] [Indexed: 07/28/2024] Open
Abstract
COVID-19 is a multisystem disease with many clinical manifestations, including liver damage and inflammation. The objective of this study is to analyze inflammation biomarkers in relation to the clinical outcome and respiratory symptoms of COVID-19. This is a retrospective cohort of patients with COVID-19 admitted to the Hospital Regional do Baixo Amazonas from 2020 to 2022. Data were collected from electronic medical records from admission to the 30th day of hospitalization and soon after hospital discharge. A total of 397 patients were included in the study. In the longitudinal follow-up of liver markers, a significant difference was found for AST on day 14, with a higher median in the death group. Among the hematological markers, lymphopenia was observed throughout the follow-up, with the death group having the most altered values. When comparing the evolution of biomarkers in the Non-Invasive Ventilation (NIV) and Invasive Mechanical Ventilation (IMV) groups, AST showed a significant difference only on day 14 and GGT on day 1, being greater in the IMV group, and indirect bilirubin on day 7 being more altered in the NIV group. In conclusion, death during hospitalization or a more severe form of COVID-19 was related to significant changes in liver and inflammatory biomarkers.
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Affiliation(s)
- Carla Sousa da Silva
- Programa de Pós-Graduação em Ciências da Saúde, Instituto de Saúde Coletiva, Universidade Federal do Oeste do Pará (UFOPA), Santarém 66075-110, Brazil; (C.S.d.S.); (L.L.S.R.)
- Laboratório de Hepatites Virais, Instituto Oswaldo Cruz (IOC/Fiocruz), Rio de Janeiro 21040-360, Brazil;
| | | | | | - Deliane dos Santos Soares
- Residência Multiprofissional em Estratégia Saúde da Família para as Populações do Baixo Amazonas, Instituto de Saúde Coletiva, Universidade Federal do Oeste do Pará (UFOPA), Santarém 66075-110, Brazil;
| | - Yasmin Garcia Silva Corrêa
- Instituto de Biodiversidade e Florestas, Universidade Federal do Oeste do Pará (UFOPA), Santarém 66075-110, Brazil;
| | - Lucas Lima da Silva
- Laboratório de Hepatites Virais, Instituto Oswaldo Cruz (IOC/Fiocruz), Rio de Janeiro 21040-360, Brazil;
| | - Vanessa Salete de Paula
- Laboratório de Virologia e Parasitologia Molecular, Instituto Oswaldo Cruz (IOC/Fiocruz), Rio de Janeiro 21040-360, Brazil;
| | - Luana Lorena Silva Rodrigues
- Programa de Pós-Graduação em Ciências da Saúde, Instituto de Saúde Coletiva, Universidade Federal do Oeste do Pará (UFOPA), Santarém 66075-110, Brazil; (C.S.d.S.); (L.L.S.R.)
- Laboratório de Aids e Imunologia Molecular, Instituto Oswaldo Cruz (IOC/Fiocruz), Rio de Janeiro 21040-360, Brazil
| | - Livia Melo Villar
- Laboratório de Hepatites Virais, Instituto Oswaldo Cruz (IOC/Fiocruz), Rio de Janeiro 21040-360, Brazil;
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10
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Inayat F, Patel P, Ali H, Afzal A, Tahir H, Chaudhry A, Ishtiaq R, Rehman AU, Darji K, Afzal MS, Nawaz G, Giammarino A, Satapathy SK. Impact of COVID-19 on liver transplant recipients: A nationwide cohort study evaluating hospitalization, transplant rejection, and inpatient mortality. World J Transplant 2024; 14:90866. [PMID: 38947960 PMCID: PMC11212588 DOI: 10.5500/wjt.v14.i2.90866] [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: 12/18/2023] [Revised: 03/22/2024] [Accepted: 04/23/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has posed a major public health concern worldwide. Patients with comorbid conditions are at risk of adverse outcomes following COVID-19. Solid organ transplant recipients with concurrent immunosuppression and comorbidities are more susceptible to a severe COVID-19 infection. It could lead to higher rates of inpatient complications and mortality in this patient population. However, studies on COVID-19 outcomes in liver transplant (LT) recipients have yielded inconsistent findings. AIM To evaluate the impact of the COVID-19 pandemic on hospital-related outcomes among LT recipients in the United States. METHODS We conducted a retrospective cohort study using the 2019-2020 National Inpatient Sample database. Patients with primary LT hospitalizations and a secondary COVID-19 diagnosis were identified using the International Classification of Diseases, Tenth Revision coding system. The primary outcomes included trends in LT hospitalizations before and during the COVID-19 pandemic. Secondary outcomes included comparative trends in inpatient mortality and transplant rejection in LT recipients. RESULTS A total of 15720 hospitalized LT recipients were included. Approximately 0.8% of patients had a secondary diagnosis of COVID-19 infection. In both cohorts, the median admission age was 57 years. The linear trends for LT hospitalizations did not differ significantly before and during the pandemic (P = 0.84). The frequency of in-hospital mortality for LT recipients increased from 1.7% to 4.4% between January 2019 and December 2020. Compared to the pre-pandemic period, a higher association was noted between LT recipients and in-hospital mortality during the pandemic, with an odds ratio (OR) of 1.69 [95% confidence interval (CI): 1.55-1.84), P < 0.001]. The frequency of transplant rejections among hospitalized LT recipients increased from 0.2% to 3.6% between January 2019 and December 2020. LT hospitalizations during the COVID-19 pandemic had a higher association with transplant rejection than before the pandemic [OR: 1.53 (95%CI: 1.26-1.85), P < 0.001]. CONCLUSION The hospitalization rates for LT recipients were comparable before and during the pandemic. Inpatient mortality and transplant rejection rates for hospitalized LT recipients were increased during the COVID-19 pandemic.
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Affiliation(s)
- Faisal Inayat
- Department of Internal Medicine, Allama Iqbal Medical College, Lahore, Punjab 54550, Pakistan
| | - Pratik Patel
- Division of Gastroenterology, Mather Hospital and Zucker School of Medicine at Hofstra University, Port Jefferson, NY 11777, United States
| | - Hassam Ali
- Division of Gastroenterology and Hepatology, East Carolina University Brody School of Medicine, Greenville, NC 27834, United States
| | - Arslan Afzal
- Division of Gastroenterology and Hepatology, East Carolina University Brody School of Medicine, Greenville, NC 27834, United States
| | - Hamza Tahir
- Department of Internal Medicine, Jefferson Einstein Hospital, Philadelphia, PA 19141, United States
| | - Ahtshamullah Chaudhry
- Department of Internal Medicine, St. Dominic's Hospital, Jackson, MS 39216, United States
| | - Rizwan Ishtiaq
- Department of Internal Medicine, Saint Francis Hospital and Medical Center, Hartford, CT 06105, United States
| | - Attiq Ur Rehman
- Division of Hepatology, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18711, United States
| | - Kishan Darji
- Department of Internal Medicine, Campbell University and Cape Fear Valley Medical Center, Fayetteville, NC 28301, United States
| | - Muhammad Sohaib Afzal
- Department of Internal Medicine, Louisiana State University Health, Shreveport, LA 71103, United States
| | - Gul Nawaz
- Department of Internal Medicine, Allama Iqbal Medical College, Lahore, Punjab 54550, Pakistan
| | - Alexa Giammarino
- Department of Internal Medicine, North Shore University Hospital and Zucker School of Medicine at Hofstra University, Manhasset, NY 11030, United States
| | - Sanjaya K Satapathy
- Division of Hepatology, North Shore University Hospital and Zucker School of Medicine at Hofstra University, Manhasset, NY 11030, United States
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11
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Oncu S, Korkmaz D. Evaluation of the relationship of treatment and vaccination with prognosis in patients with a diagnosis of COVID-19. Inflammopharmacology 2024; 32:1817-1826. [PMID: 38493271 PMCID: PMC11136715 DOI: 10.1007/s10787-024-01457-4] [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: 02/07/2024] [Accepted: 03/01/2024] [Indexed: 03/18/2024]
Abstract
PURPOSE Coronavirus disease 2019 (COVID-19) has affected millions of people worldwide and caused mortality. Many factors have been reported to affect the prognosis of COVID-19. In this study, we aimed to investigate the effects of drug therapy and vaccination on prognosis in patients hospitalized with a COVID-19 diagnosis. METHODS In this single-center, cross-sectional study, data were retrospectively collected from patients receiving inpatient treatment at a university hospital with a diagnosis of COVID-19 between January 1, 2020, and April 30, 2022. The patients' demographic and clinical characteristics were recorded. The Chi-square, Cox and logistic regression was performed, P < 0.05 was considered statistically significant. RESULTS Total 1723 patients (50.1% were men, mean age: 60.6 ± 16.90) who had not been vaccinated rate was 27.0% (> 3 doses: 45.7%). Mortality rate was 17.0%. Increasing age, male, a high Charlson Comorbidity Index (CCI), and no vaccination significantly increased mortality (P < 0.05). The mortality rate was significantly lower in the chloroquine treatment group than in the other treatment groups. Increasing age, male, and a high CCI were determined to be factors that significantly increased the length of hospital stay (LOHS). LOHS found to be significantly lower in the favipiravir or chloroquine groups compared to the remaining treatment groups (P < 0.001). Both mortality and the LOHS significantly differed according to AST, d-dimer, ferritin, and GFR. CONCLUSION This study primarily investigated the effect of treatment and vaccination on the prognosis of COVID-19. This was determined to be prepared for another potential pandemic that may arise due to COVID-19.
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Affiliation(s)
- Seyma Oncu
- Department of Pharmacology, Faculty of Medicine, Afyonkarahisar Health Sciences University, Afyonkarahisar, 03030, Turkey.
| | - Derya Korkmaz
- Department of Infectious Disease, Faculty of Medicine, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey
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12
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Bota AV, Bratosin F, Bandi SSS, Bogdan I, Razvan DV, Toma AO, Indries MF, Csep AN, Cotoraci C, Prodan M, Marc F, Ignuta F, Marincu I. A Comparative Analysis of Liver Injury Markers in Post-COVID Syndrome among Elderly Patients: A Prospective Study. J Clin Med 2024; 13:1149. [PMID: 38398462 PMCID: PMC10889217 DOI: 10.3390/jcm13041149] [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: 12/23/2023] [Revised: 02/07/2024] [Accepted: 02/14/2024] [Indexed: 02/25/2024] Open
Abstract
BACKGROUND In the wake of the global COVID-19 pandemic, understanding its prolonged impact on vulnerable populations has become a critical area of investigation. This study aimed to elucidate the distinctive post-acute sequelae of SARS-CoV-2 infection (PASC) and liver injury in Romania's elderly population, hypothesizing unique demographic, clinical, and healthcare factors influencing the manifestation. METHODS A longitudinal design was employed, enrolling COVID-19 patients from the Victor Babes Hospital for Infectious Diseases and Pulmonology in Timisoara, Romania. Participants were stratified into three groups based on age and Long COVID status. The study focused on a variety of demographic, clinical, and biological parameters, including liver function tests, to assess the trajectory and severity of liver injury over six months post discharge. RESULTS Involving 238 participants, the study revealed a significant increase in the duration of hospitalization for those over 65 (15.8 ± 8.2 days) compared to younger groups (p < 0.001). Notably, elderly Long COVID patients exhibited a marked elevation in liver enzymes post discharge, with median ΔALT and ΔAST of 24.1 U/L and 30.2 U/L, respectively, suggesting ongoing liver injury (p < 0.001). Significant metabolic disruptions were observed, with the ΔFasting glucose showing a substantial median decrease of 21.1 mmol/L in the elderly group (p < 0.001). A pronounced reduction in ΔGGT (16.7 U/L) and ΔLDH (48.7 U/L) was noted, indicating a recovery in liver function and reduced tissue damage (p < 0.001). Coagulation profiles and liver fibrosis risk scores, particularly ΔFIB-4 and ΔAPRI, also significantly improved post discharge, indicating a reduced risk of ongoing liver complications. CONCLUSION This study confirms the hypothesis of more severe PASC and liver injury among the elderly Romanian population. Significant improvements post discharge suggest a degree of recovery, yet the persistent alterations in liver enzymes, glucose metabolism, and fibrosis risk scores call for continued monitoring and tailored management strategies.
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Affiliation(s)
- Adrian Vasile Bota
- Methodological and Infectious Diseases Research Center, Department of Infectious Diseases, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania; (A.V.B.); (F.B.); (I.B.); (D.V.R.); (F.I.); (I.M.)
- Doctoral School, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania;
- Department of Hematology, Faculty of Medicine, “Vasile Goldis” Western University, Bulevardul Revolutiei 94, 310025 Arad, Romania;
| | - Felix Bratosin
- Methodological and Infectious Diseases Research Center, Department of Infectious Diseases, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania; (A.V.B.); (F.B.); (I.B.); (D.V.R.); (F.I.); (I.M.)
- Doctoral School, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania;
- Discipline of Infectious Diseases, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Satya Sai Sri Bandi
- Malla Reddy Institute of Medical Sciences, Suraram Main Road 138, Hyderabad 500055, India;
| | - Iulia Bogdan
- Methodological and Infectious Diseases Research Center, Department of Infectious Diseases, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania; (A.V.B.); (F.B.); (I.B.); (D.V.R.); (F.I.); (I.M.)
- Doctoral School, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania;
- Discipline of Infectious Diseases, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - David Vladut Razvan
- Methodological and Infectious Diseases Research Center, Department of Infectious Diseases, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania; (A.V.B.); (F.B.); (I.B.); (D.V.R.); (F.I.); (I.M.)
- Doctoral School, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania;
| | - Ana-Olivia Toma
- Discipline of Dermatology, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Mirela Florica Indries
- Department of Psycho-Neuroscience and Recovery, Faculty of Medicine and Pharmacy, University of Oradea, Strada Universitatii 1, 410087 Oradea, Romania;
| | - Andrei Nicolae Csep
- Department of Psycho-Neuroscience and Recovery, Faculty of Medicine and Pharmacy, University of Oradea, Strada Universitatii 1, 410087 Oradea, Romania;
| | - Coralia Cotoraci
- Department of Hematology, Faculty of Medicine, “Vasile Goldis” Western University, Bulevardul Revolutiei 94, 310025 Arad, Romania;
| | - Mihaela Prodan
- Doctoral School, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania;
- Department of Plastic Surgery, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Felicia Marc
- Department of Medical Sciences, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | - Flavia Ignuta
- Methodological and Infectious Diseases Research Center, Department of Infectious Diseases, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania; (A.V.B.); (F.B.); (I.B.); (D.V.R.); (F.I.); (I.M.)
- Doctoral School, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania;
| | - Iosif Marincu
- Methodological and Infectious Diseases Research Center, Department of Infectious Diseases, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania; (A.V.B.); (F.B.); (I.B.); (D.V.R.); (F.I.); (I.M.)
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13
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Teschke R, Eickhoff A. COVID-19 and suspected drug-induced liver injury. FEATURES, TRANSMISSION, DETECTION, AND CASE STUDIES IN COVID-19 2024:267-285. [DOI: 10.1016/b978-0-323-95646-8.00047-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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14
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Abolfazli S, Ebrahimi N, Morabi E, Asgari Yazdi MA, Zengin G, Sathyapalan T, Jamialahmadi T, Sahebkar A. Hydrogen Sulfide: Physiological Roles and Therapeutic Implications against COVID-19. Curr Med Chem 2024; 31:3132-3148. [PMID: 37138436 DOI: 10.2174/0929867330666230502111227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 01/19/2023] [Accepted: 02/10/2023] [Indexed: 05/05/2023]
Abstract
The COVID-19 pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) poses a major menace to economic and public health worldwide. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) are two host proteins that play an essential function in the entry of SARS-- COV-2 into host cells. Hydrogen sulfide (H2S), a new gasotransmitter, has been shown to protect the lungs from potential damage through its anti-inflammatory, antioxidant, antiviral, and anti-aging effects. It is well known that H2S is crucial in controlling the inflammatory reaction and the pro-inflammatory cytokine storm. Therefore, it has been suggested that some H2S donors may help treat acute lung inflammation. Furthermore, recent research illuminates a number of mechanisms of action that may explain the antiviral properties of H2S. Some early clinical findings indicate a negative correlation between endogenous H2S concentrations and COVID-19 intensity. Therefore, reusing H2S-releasing drugs could represent a curative option for COVID-19 therapy.
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Affiliation(s)
- Sajad Abolfazli
- Student Research Committee, School of Pharmacy, Mazandaran University of Medical Science, Sari, Iran
| | - Nima Ebrahimi
- Student Research Committee, School of Pharmacy, Mashhad University of Medical Science, Mashhad, Iran
| | - Etekhar Morabi
- Student Research Committee, School of Pharmacy, Shahid Sadoughi University of Medical Science, Yazd, Iran
| | | | - Gokhan Zengin
- Department of Biology, Science Faculty, Selcuk University, Konya 42130, Turkey
| | - Thozhukat Sathyapalan
- Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, United Kingdom of Great Britain and Northern Ireland
| | - Tannaz Jamialahmadi
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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15
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Lovero R, Charitos IA, Topi S, Castellaneta F, Cazzolla AP, Colella M. Current Views About the Link between SARS-CoV-2 and the Liver: Friends or Foe? Endocr Metab Immune Disord Drug Targets 2024; 24:642-650. [PMID: 37846575 DOI: 10.2174/0118715303251985231009050626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Revised: 09/07/2023] [Accepted: 09/12/2023] [Indexed: 10/18/2023]
Abstract
The emergence of the novel coronavirus and the pandemic resulting from its spread have led to significant negative impacts on health, economy, relationships, and others. Particularly in the field of hospital care, the need for a greater number of patients has led to a breakdown of the system. Gastrointestinal manifestations are common in SARS-COV 2 patients, while 10% of those who are sick exhibit symptoms only from gastrointestinal without any manifestation on the part of the respiratory tract. The main manifestations are nausea, vomiting, diarrhoea, and anorexia. It is also interesting to note that biochemical liver disorder is a frequent finding and is associated with a worse prognosis and higher probability admission to intensive care. It was also observed that RNA from the virus was found in the stool several days after the tests came back negative pulmonary secretions, while rectal swab virus detection methods were used with a lower but comparable sensitivity to that of nasal swabs. Gastrointestinal symptoms in SARS-COV 2 infection are common and their search should be part of the initial diagnosis approach and have a connection with the gut microbiota dysbiosis and this can lead to an alteration of the gut/liver axis.
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Affiliation(s)
- Roberto Lovero
- Clinical Pathology Unit, AOU Policlinico Consorziale di Bari - Ospedale Giovanni XXIII, Bari 70124, Italy
| | | | - Skender Topi
- Department of Clinical Disciplines, University of Elbasan, Elbasan, 3001, Albania
| | - Francesca Castellaneta
- Clinical Pathology Unit, AOU Policlinico Consorziale di Bari - Ospedale Giovanni XXIII, Bari 70124, Italy
| | - Angela Pia Cazzolla
- Department of Clinical and Experimental Medicine, Università degli Studi di Foggia, Foggia, 71122, Italy
| | - Marica Colella
- Interdisciplinary Department of Medicine, Section of Microbiology and Virology, Università degli Studi di Bari, 70124, Bari, Italy
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16
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Paris D, Palomba L, Albertini MC, Tramice A, Motta L, Giammattei E, Ambrosino P, Maniscalco M, Motta A. The biomarkers' landscape of post-COVID-19 patients can suggest selective clinical interventions. Sci Rep 2023; 13:22496. [PMID: 38110483 PMCID: PMC10728085 DOI: 10.1038/s41598-023-49601-4] [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: 12/15/2022] [Accepted: 12/10/2023] [Indexed: 12/20/2023] Open
Abstract
In COVID-19 clinical symptoms can persist even after negativization also in individuals who have had mild or moderate disease. We here investigated the biomarkers that define the post-COVID-19 clinical state analyzing the exhaled breath condensate (EBC) of 38 post COVID-19 patients and 38 sex and age-matched healthy controls via nuclear magnetic resonance (NMR)-based metabolomics. Predicted gene-modulated microRNAs (miRNAs) related to COVID-19 were quantified from EBC of 10 patients and 10 controls. Finally, clinical parameters from all post-COVID-19 patients were correlated with metabolomic data. Post-COVID-19 patients and controls showed different metabolic phenotype ("metabotype"). From the metabolites, by using enrichment analysis we identified miRNAs that resulted up-regulated (hsa-miR146a-5p) and down-regulated (hsa-miR-126-3p and hsa-miR-223-3p) in post-COVID-19. Taken together, our multiomics data indicate that post-COVID-19 patients before rehabilitation are characterized by persistent inflammation, dysregulation of liver, endovascular thrombotic and pulmonary processes, and physical impairment, which should be the primary clinical targets to contrast the post-acute sequelae of COVID-19.
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Affiliation(s)
- Debora Paris
- Institute of Biomolecular Chemistry, National Research Council, 80078, Pozzuoli (Naples), Italy
| | - Letizia Palomba
- Department of Biomolecular Sciences, "Carlo Bo" University, 61029, Urbino, Italy
| | | | - Annabella Tramice
- Institute of Biomolecular Chemistry, National Research Council, 80078, Pozzuoli (Naples), Italy
| | - Lorenzo Motta
- Neuroradiology Unit, Ospedale Santa Maria Della Misericordia, 45100, Rovigo, Italy
- IRCCS Istituto Delle Scienze Neurologiche (Padiglione G), via Altura 3, 40139, Bologna, Italy
| | - Eleonora Giammattei
- Department of Biomolecular Sciences, "Carlo Bo" University, 61029, Urbino, Italy
| | - Pasquale Ambrosino
- Directorate of Telese Terme Institute, Istituti Clinici Scientifici Maugeri IRCCS, 82037, Telese Terme (Benevento), Italy
| | - Mauro Maniscalco
- Pulmonary Rehabilitation Unit of the Telese Terme Institute, Istituti Clinici Scientifici Maugeri IRCCS, 82037, Telese Terme (Benevento), Italy.
- Department of Clinical Medicine and Surgery, Section of Respiratory Disease, University of Naples Federico II, 80131, Naples, Italy.
| | - Andrea Motta
- Institute of Biomolecular Chemistry, National Research Council, 80078, Pozzuoli (Naples), Italy.
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17
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Sambommatsu Y, Mouch C, Kulkarni AV, Bruno DA, Eslami M, Imai D, Lee SD, Khan AA, Sharma A, Saeed M, Cotterell AH, Levy MF, Morales MK, Montenovo MI, Rao PN, Reddy R, Menon B, Kumaran V. Liver transplantation for post-COVID-19 cholangiopathy: A case series. Clin Transplant 2023; 37:e15141. [PMID: 37755152 DOI: 10.1111/ctr.15141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 09/17/2023] [Indexed: 09/28/2023]
Abstract
BACKGROUND Post-COVID-19 cholangiopathy is an emerging cholestatic liver disease observed in patients recovering from severe COVID-19 infection. Its prognosis is poor, necessitating liver transplantation in some cases. This study aimed to investigate the outcomes of liver transplantation for post-COVID-19 cholangiopathy. METHODS Seven patients who underwent liver transplantation for post-COVID-19 cholangiopathy at three institutions between 2020 and 2022 were included in this retrospective multi-center case series. RESULTS At the time of initial COVID-19 infection, all patients developed acute respiratory distress syndrome, and six patients (86%) required ICU admission. Median time intervals from the initial COVID-19 diagnosis to the diagnosis of post-COVID-19 cholangiopathy and liver transplantation were 4 and 12 months, respectively. Four patients underwent living donor liver transplantation, and three patients underwent deceased donor liver transplantation. The median MELD score was 22 (range, 10-38). No significant intraoperative complications were observed. The median ICU and hospital stays were 2.5 and 12.5 days, respectively. One patient died due to respiratory failure 5 months after liver transplantation. Currently, the patient and graft survival rate is 86% at a median follow-up of 11 months. CONCLUSIONS Liver transplantation is a viable option for patients with post-COVID-19 cholangiopathy with acceptable outcome. Timely identification of this disease and appropriate management, including evaluation for liver transplantation, are essential.
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Affiliation(s)
- Yuzuru Sambommatsu
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Charles Mouch
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Anand V Kulkarni
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
| | - David A Bruno
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Mehdi Eslami
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Daisuke Imai
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Seung Duk Lee
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Aamir A Khan
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Amit Sharma
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Muhammad Saeed
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Adrian H Cotterell
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Marlon F Levy
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Megan K Morales
- Department of Internal Medicine, Division of Infectious Disease, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Martin I Montenovo
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Padaki N Rao
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Raghuram Reddy
- Department of Liver Transplantation and Hepatobiliary Surgery, Asian Institute of Gastroenterology, Hyderabad, India
| | - Balachandran Menon
- Department of Liver Transplantation and Hepatobiliary Surgery, Asian Institute of Gastroenterology, Hyderabad, India
| | - Vinay Kumaran
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
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18
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Lim JK, Njei B. Clinical and Histopathological Discoveries in Patients with Hepatic Injury and Cholangiopathy Who Have Died of COVID-19: Insights and Opportunities for Intervention. Hepat Med 2023; 15:151-164. [PMID: 37814605 PMCID: PMC10560482 DOI: 10.2147/hmer.s385133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 09/28/2023] [Indexed: 10/11/2023] Open
Abstract
The COVID-19 pandemic has had a profound impact on global health, necessitating a comprehensive understanding of its diverse manifestations. Cholangiopathy, a condition characterized by biliary dysfunction, has emerged as a significant complication in COVID-19 patients. In this review, we report the epidemiology of COVID-19, describe the hepatotropism of SARS-CoV-2, and present the histopathology of acute liver injury (ALI) in COVID-19. Additionally, we explore the relationship between pre-existing chronic liver disease and COVID-19, shedding light on the increased susceptibility of these individuals to develop cholangiopathy. Through an in-depth analysis of cholangiopathy in COVID-19 patients, we elucidate its clinical manifestations, diagnostic criteria, and underlying pathogenesis involving inflammation, immune dysregulation, and vascular changes. Furthermore, we provide a summary of studies investigating post-COVID-19 cholangiopathy, highlighting the long-term effects and potential management strategies for this condition, and discussing opportunities for intervention, including therapeutic targets, diagnostic advancements, supportive care, and future research needs.
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Affiliation(s)
- Joseph K Lim
- Yale Liver Center and Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
| | - Basile Njei
- Yale Liver Center and Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
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19
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Romano C, Cozzolino D, Nevola R, Abitabile M, Carusone C, Cinone F, Cuomo G, Nappo F, Sellitto A, Umano GR, Adinolfi LE, Marrone A, Rinaldi L. Liver Involvement during SARS-CoV-2 Infection Is Associated with a Worse Respiratory Outcome in COVID-19 Patients. Viruses 2023; 15:1904. [PMID: 37766310 PMCID: PMC10537641 DOI: 10.3390/v15091904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 09/07/2023] [Accepted: 09/09/2023] [Indexed: 09/29/2023] Open
Abstract
Coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may be complicated by life-threatening interstitial pneumonia. SARS-CoV-2 infection may also damage several tissues and/or organs beyond the lungs, including the liver. However, controversy still exists as to whether SARS-CoV-2-induced liver alterations can have an impact on the outcome of COVID-19. The aim of this study was therefore to assess whether SARS-CoV-2-infected patients with liver abnormalities at the time of hospital referral had a worse outcome with respect to patients with no liver biochemistry alterations. To this end, the medical records of 123 patients admitted to our COVID center between the end of 2020 and spring 2021 were retrospectively reviewed. Patients were divided into two groups: those with normal liver biochemistries (group 1, 77 patients) and those with altered liver function tests (group 2, 46 patients). Serum levels of aminotransferases (AST and ALT) and bile duct cell injury markers (γ-GT and ALP) were used to dichotomize patients. A higher percentage of patients with liver enzyme alterations were found to develop COVID-19 pneumonia with respect to group 1 patients (74% vs. 65%); moreover, they needed more days of respiratory support and, more importantly, more intensive administration of supplemental oxygen. A statistically significant correlation was also found between aminotransferase levels and duration of respiratory support. The mortality rate was not superior in group 2 vs. group 1 patients. In conclusion, liver abnormalities on admission predisposed COVID-19 patients to development of more severe interstitial pneumonia, because of a longer requirement for supplemental oxygen and a more intensive respiratory support, indicative of a worse disease evolution in these patients.
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Affiliation(s)
- Ciro Romano
- COVID Center, Division of Internal Medicine, Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (R.N.); (A.M.); (L.R.)
| | - Domenico Cozzolino
- Department of Precision Medicine, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (D.C.); (G.C.)
| | - Riccardo Nevola
- COVID Center, Division of Internal Medicine, Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (R.N.); (A.M.); (L.R.)
| | - Marianna Abitabile
- COVID Center, Division of Internal Medicine, Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (R.N.); (A.M.); (L.R.)
| | - Caterina Carusone
- COVID Center, Division of Internal Medicine, Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (R.N.); (A.M.); (L.R.)
| | - Francesca Cinone
- COVID Center, Division of Internal Medicine, Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (R.N.); (A.M.); (L.R.)
| | - Giovanna Cuomo
- Department of Precision Medicine, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (D.C.); (G.C.)
| | - Francesco Nappo
- COVID Center, Division of Internal Medicine, Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (R.N.); (A.M.); (L.R.)
| | - Ausilia Sellitto
- COVID Center, Division of Internal Medicine, Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (R.N.); (A.M.); (L.R.)
| | - Giuseppina Rosaria Umano
- Department of Woman & Child Health and General and Specialist Surgery, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy;
| | - Luigi Elio Adinolfi
- COVID Center, Division of Internal Medicine, Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (R.N.); (A.M.); (L.R.)
| | - Aldo Marrone
- COVID Center, Division of Internal Medicine, Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (R.N.); (A.M.); (L.R.)
| | - Luca Rinaldi
- COVID Center, Division of Internal Medicine, Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (R.N.); (A.M.); (L.R.)
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20
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Backer S, Khanna D. The Lasting Effects of COVID-19 on the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Cureus 2023; 15:e45231. [PMID: 37842470 PMCID: PMC10576539 DOI: 10.7759/cureus.45231] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 09/13/2023] [Indexed: 10/17/2023] Open
Abstract
It is estimated that around 30% of the population living in Western countries has metabolic dysfunction-associated steatotic liver disease (MASLD), a spectrum of pathology (not attributed to alcohol/substance intake) initiated by steatosis and progression toward inflammation and irreversible fibrosis metabolic dysfunction-associated steatohepatitis (MASH). With inflammation being a key component of the transition to MASH, it raises the question of whether the ongoing COVID-19 pandemic, which has notoriously induced hyperinflammatory states, may influence the progression of MASLD. Specifically, it remains unclear if the potential chronic sequelae of COVID-19 in patients who recovered from it may increase the predisposition for MASH. Since MASH maintains a high risk for hepatocellular carcinoma, liver failure, and the need for a liver transplant, the potential additive effects of COVID-19 could prove critical to study. Thus, the objective of this study was to conduct a literature review to examine if COVID-19 could have chronic sequelae that affect the progression of MASLD pathogenesis. It was hypothesized that severe cases of COVID-19 could induce systemic inflammation, metabolic changes, and lasting gut microbiome alterations that lead to inflammatory and fibrotic changes in the liver, similar to those seen in MASH. A scoping review of the literature was conducted utilizing the PubMed database. Studies that examined hepatobiliary pathology, gut microbiome, systemic inflammation, metabolic changes, drug-induced liver injury (DILI), and hypoxia seen in COVID-19 were included. Human studies of adult cohorts, animal models, and in vitro experiments were included. Genetic components of MASLD were not examined. Exclusion criteria also encompassed any studies not referencing the hepatobiliary, gastrointestinal tract, portal system, or systemic circulation. Findings indicated a frequent trend of elevated liver enzymes, mild steatosis, Kupffer cell hyperplasia, and hepatobiliary congestion. It was found that direct cytopathic effects on hepatocytes were unlikely, but the direct viral insult of cholangiocytes was a potential complication. High serum levels of IL-1, TNF-a, and MCP-1, in COVID-19 were found as potential risk factors for MASH development. Hypoxia, altered lipid metabolism, and iatrogenic DILI were also proposed as potential precipitators of MASH development. Notably, lasting changes in gut microbiome were also frequently observed and correlated closely with those seen in MASH.
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Affiliation(s)
- Sean Backer
- Foundational Sciences, Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Clearwater, USA
| | - Deepesh Khanna
- Foundational Sciences, Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Clearwater, USA
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21
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Miele L, Dajko M, Savino MC, Capocchiano ND, Calvez V, Liguori A, Masciocchi C, Vetrone L, Mignini I, Schepis T, Marrone G, Biolato M, Cesario A, Patarnello S, Damiani A, Grieco A, Valentini V, Gasbarrini A. Fib-4 score is able to predict intra-hospital mortality in 4 different SARS-COV2 waves. Intern Emerg Med 2023; 18:1415-1427. [PMID: 37491564 PMCID: PMC10412472 DOI: 10.1007/s11739-023-03310-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 05/10/2023] [Indexed: 07/27/2023]
Abstract
Increased values of the FIB-4 index appear to be associated with poor clinical outcomes in COVID-19 patients. This study aimed to develop and validate predictive mortality models, using data upon admission of hospitalized patients in four COVID-19 waves between March 2020 and January 2022. A single-center cohort study was performed on consecutive adult patients with Covid-19 admitted at the Fondazione Policlinico Gemelli IRCCS (Rome, Italy). Artificial intelligence and big data processing were used to retrieve data. Patients and clinical characteristics of patients with available FIB-4 data derived from the Gemelli Generator Real World Data (G2 RWD) were used to develop predictive mortality models during the four waves of the COVID-19 pandemic. A logistic regression model was applied to the training and test set (75%:25%). The model's performance was assessed by receiver operating characteristic (ROC) curves. A total of 4936 patients were included. Hypertension (38.4%), cancer (12.15%) and diabetes (16.3%) were the most common comorbidities. 23.9% of patients were admitted to ICU, and 12.6% had mechanical ventilation. During the study period, 762 patients (15.4%) died. We developed a multivariable logistic regression model on patient data from all waves, which showed that the FIB-4 score > 2.53 was associated with increased mortality risk (OR = 4.53, 95% CI 2.83-7.25; p ≤ 0.001). These data may be useful in the risk stratification at the admission of hospitalized patients with COVID-19.
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Affiliation(s)
- Luca Miele
- Dipartimento di Scienze Mediche e Chirurgiche (DiSMeC), Fondazione Policlinico Gemelli IRCCS, Università Cattolica del S. Cuore, 8, Largo Gemelli, 00168 Rome, Italy
- Department of Medicina e Chirurgia Traslazionale, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Marianxhela Dajko
- Dipartimento di Scienze Mediche e Chirurgiche (DiSMeC), Fondazione Policlinico Gemelli IRCCS, Università Cattolica del S. Cuore, 8, Largo Gemelli, 00168 Rome, Italy
| | - Maria Chiara Savino
- Department Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Gemelli IRCCS, Rome, Italy
| | - Nicola D. Capocchiano
- Gemelli Generator Real World Data Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Valentino Calvez
- Department of Medicina e Chirurgia Traslazionale, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Antonio Liguori
- Department of Medicina e Chirurgia Traslazionale, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Carlotta Masciocchi
- Gemelli Generator Real World Data Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Lorenzo Vetrone
- Department of Medicina e Chirurgia Traslazionale, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Irene Mignini
- Department of Medicina e Chirurgia Traslazionale, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Tommaso Schepis
- Department of Medicina e Chirurgia Traslazionale, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Giuseppe Marrone
- Department of Medicina e Chirurgia Traslazionale, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Marco Biolato
- Department of Medicina e Chirurgia Traslazionale, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Alfredo Cesario
- Gemelli Digital Medicine and Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Stefano Patarnello
- Gemelli Generator Real World Data Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Andrea Damiani
- Gemelli Generator Real World Data Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Antonio Grieco
- Dipartimento di Scienze Mediche e Chirurgiche (DiSMeC), Fondazione Policlinico Gemelli IRCCS, Università Cattolica del S. Cuore, 8, Largo Gemelli, 00168 Rome, Italy
- Department of Medicina e Chirurgia Traslazionale, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Vincenzo Valentini
- Department Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Gemelli IRCCS, Rome, Italy
| | - Antonio Gasbarrini
- Dipartimento di Scienze Mediche e Chirurgiche (DiSMeC), Fondazione Policlinico Gemelli IRCCS, Università Cattolica del S. Cuore, 8, Largo Gemelli, 00168 Rome, Italy
- Department of Medicina e Chirurgia Traslazionale, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Gemelli against COVID Group
- Dipartimento di Scienze Mediche e Chirurgiche (DiSMeC), Fondazione Policlinico Gemelli IRCCS, Università Cattolica del S. Cuore, 8, Largo Gemelli, 00168 Rome, Italy
- Department of Medicina e Chirurgia Traslazionale, Università Cattolica Del Sacro Cuore, Rome, Italy
- Department Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Gemelli IRCCS, Rome, Italy
- Gemelli Generator Real World Data Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Gemelli Digital Medicine and Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
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22
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Parajuli P, Sabo R, Alsaadawi R, Robinson A, French E, Sterling RK. Fibrosis-4 (FIB-4) index as a predictor for mechanical ventilation and 30-day mortality across COVID-19 variants. J Clin Transl Sci 2023; 7:e213. [PMID: 38028347 PMCID: PMC10643913 DOI: 10.1017/cts.2023.594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 07/07/2023] [Accepted: 07/11/2023] [Indexed: 12/01/2023] Open
Abstract
Background The Fibrosis-4 (FIB-4) index, a simple index that includes age, liver enzymes, and platelet count has been studied as a tool to identify patients at a risk of requiring mechanical ventilation due to its high negative predictive value. It is unknown if FIB-4 remains useful to predict the severity of respiratory disease requiring mechanical ventilation amongst new Coronavirus disease 2019 (COVID-19) variants and whether a relationship also exists between FIB-4 and 30-day mortality. The main objective was to determine if FIB-4 can predict mechanical ventilation requirements and 30-day mortality from COVID-19 across variants including Alpha, Delta, and Omicron. Methods This was a population-based, retrospective cohort analysis of 232,364 hospitalized patients in the National COVID-19 Cohort Collaborative between the age of 18-90 who tested positive for COVID-19 between April 27, 2020 and June 25, 2022. The primary outcome was association between FIB-4 and need for mechanical ventilation. Secondary measures included the association of FIB-4 with 30-day mortality. Results A FIB-4 > 2.67 had 1.8 times higher odds of requiring mechanical ventilation across all variants of COVID-19 (OR 1.81; 95% CI: [1.76, 1.86]). The area under the ROC curve showed high diagnostic accuracy with values ranging between 0.79 (Omicron wave) and 0.97 (delta wave). Increased FIB-4 was associated with 30-day mortality across the variates. Conclusion The FIB-4 was consistently associated with both increased utilization of mechanical ventilation and 30-day mortality among COVID-19 patients across all waves in both adjusted and unadjusted models. This provides a simple tool for risk-stratification for front-line health care professionals.
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Affiliation(s)
- Priyanka Parajuli
- Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Roy Sabo
- C. Kenneth and Dianne Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, USA
- Department of Biostatistics, Virginia Commonwealth University, Richmond, VA, USA
| | - Rasha Alsaadawi
- C. Kenneth and Dianne Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, USA
- Department of Biostatistics, Virginia Commonwealth University, Richmond, VA, USA
| | - Amanda Robinson
- C. Kenneth and Dianne Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, USA
| | - Evan French
- C. Kenneth and Dianne Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, USA
| | - Richard K. Sterling
- Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
- C. Kenneth and Dianne Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, USA
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, VA, USA
- Division of Infectious Disease, Virginia Commonwealth University, Richmond, VA, USA
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23
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Berger DS, Galyean A, Nguyen K, Alshak N, Blumenthal E. A Case of Significant Transaminitis with Liver Biopsy in a Pregnant Patient with COVID-19. AJP Rep 2023; 13:e78-e81. [PMID: 38033600 PMCID: PMC10684339 DOI: 10.1055/s-0043-1777099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 08/30/2023] [Indexed: 12/02/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has led to a global health crisis. The virus can cause varying severity of liver injury, but the mechanism has not yet been elucidated, especially in pregnancy. We present a morbidly obese 30-year-old woman with COVID-19 at 28 weeks' gestation complicated by significant transaminitis with peak liver enzymes levels of 501/1,313 (aspartate aminotransferase/alanine aminotransferase). Liver biopsy showed reactive changes consistent with medication effect and mild steatosis. Significant transaminitis has been found in both pregnant and nonpregnant patients with COVID-19. Our case demonstrates the multifactorial nature of liver injury in COVID-19 patients including mild underlying liver steatosis combined with possible viral potentiation of medication effect.
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Affiliation(s)
- Dana Senderoff Berger
- Department of Obstetrics and Gynecology, University of California, Irvine, Orange, California
| | - Anna Galyean
- Department of Obstetrics and Gynecology, Southern California Permanente Medical Group, Pasadena, California
| | - Kelvin Nguyen
- Department of Gastroenterology, Southern California Permanente Medical Group, Pasadena, California
| | - Najeeb Alshak
- Department of Pathology, Southern California Permanente Medical Group, Pasadena, California
| | - Elizabeth Blumenthal
- Department of Obstetrics and Gynecology, Southern California Permanente Medical Group, Pasadena, California
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24
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Heston AL, Sharma V, Johnson T, Anandakrishnan A, Patel A. A Case of Severe Hepatitis in Infant Twins With COVID-19. Cureus 2023; 15:e41967. [PMID: 37588319 PMCID: PMC10427151 DOI: 10.7759/cureus.41967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/16/2023] [Indexed: 08/18/2023] Open
Abstract
We report a case of nine-month-old twins who presented with bright green diarrhea along with progressively worsening jaundice over one week. On initial evaluation, they were found to have significantly elevated liver enzymes, bilirubin, and alkaline phosphatase levels but without signs of liver failure. They were tested for multiple causes of liver injury including autoimmune and infectious etiologies, which were negative as well. Both twins were incidentally found to be positive for COVID-19 on testing per hospital protocol but did not have any respiratory symptoms. They were monitored closely during their hospital stay and showed clinical stability but with only slight improvement in abnormal lab levels. Ultimately, they were discharged with close outpatient follow-up. They demonstrated full resolution of all lab abnormalities and symptoms two months post discharge.
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Affiliation(s)
| | - Varun Sharma
- Medicine, University of Arizona College of Medicine, Phoenix, USA
| | - Taryn Johnson
- Pediatrics, Phoenix Children's Hospital, Phoenix, USA
| | | | - Ashish Patel
- Pediatric Gastroenterology, Phoenix Children's Hospital, Phoenix, USA
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25
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Imam MT, Almalki ZS, Alzahrani AR, Al-Ghamdi SS, Falemban AH, Alanazi IM, Shahzad N, Muhammad Alrooqi M, Jabeen Q, Shahid I. COVID-19 and severity of liver diseases: Possible crosstalk and clinical implications. Int Immunopharmacol 2023; 121:110439. [PMID: 37315370 PMCID: PMC10247890 DOI: 10.1016/j.intimp.2023.110439] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 05/30/2023] [Accepted: 05/31/2023] [Indexed: 06/16/2023]
Abstract
COVID-19-infected individuals and those who recovered from the infection have been demonstrated to have elevated liver enzymes or abnormal liver biochemistries, particularly with preexisting liver diseases, liver metabolic disorders, viral hepatitis, and other hepatic comorbidities. However, possible crosstalk and intricate interplay between COVID-19 and liver disease severity are still elusive, and the available data are murky and confined. Similarly, the syndemic of other blood-borne infectious diseases, chemical-induced liver injuries, and chronic hepatic diseases continued to take lives while showing signs of worsening due to the COVID-19 crisis. Moreover, the pandemic is not over yet and is transitioning to becoming an epidemic in recent years; hence, monitoring liver function tests (LFTs) and assessing hepatic consequences of COVID-19 in patients with or without liver illnesses would be of paramount interest. This pragmatic review explores the correlations between COVID-19 and liver disease severity based on abnormal liver biochemistries and other possible mechanisms in individuals of all ages from the emergence of the COVID-19 pandemic to the post-pandemic period. The review also alludes to clinical perspectives of such interactions to curb overlapping hepatic diseases in people who recovered from the infection or living with long COVID-19.
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Affiliation(s)
- Mohammad T Imam
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia
| | - Ziyad S Almalki
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia
| | - Abdullah R Alzahrani
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Saeed S Al-Ghamdi
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Alaa H Falemban
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Ibrahim M Alanazi
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Naiyer Shahzad
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | | | - Qaisar Jabeen
- Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Imran Shahid
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia.
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26
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Ritter E, Shusterman E, Prozan L, Kehat O, Weiss Meilik A, Shibolet O, Ablin JN. The Liver Can Deliver: Utility of Hepatic Function Tests as Predictors of Outcome in COVID-19, Influenza and RSV Infections. J Clin Med 2023; 12:jcm12093335. [PMID: 37176775 PMCID: PMC10179215 DOI: 10.3390/jcm12093335] [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: 04/03/2023] [Revised: 04/21/2023] [Accepted: 05/06/2023] [Indexed: 05/15/2023] Open
Abstract
BACKGROUND liver test abnormalities have been described in patients with Coronavirus-2019 (COVID-19), and hepatic involvement may correlate with disease severity. With the relaxing of COVID-19 restrictions, seasonal respiratory viruses now circulate alongside SARS-CoV-2. AIMS we aimed to compare patterns of abnormal liver function tests in patients suffering from COVID-19 infection and seasonal respiratory viruses: respiratory syncytial virus (RSV) and influenza (A and B). METHODS a retrospective cohort study was performed including 4140 patients admitted to a tertiary medical center between 2010-2020. Liver test abnormalities were classified as hepatocellular, cholestatic or mixed type. Clinical outcomes were defined as 30-day mortality and mechanical ventilation. RESULTS liver function abnormalities were mild to moderate in most patients, and mainly cholestatic. Hepatocellular injury was far less frequent but had a strong association with adverse clinical outcome in RSV, COVID-19 and influenza (odds ratio 5.29 (CI 1.2-22), 3.45 (CI 1.7-7), 3.1 (CI 1.7-6), respectively) COVID-19 and influenza patients whose liver functions did not improve or alternatively worsened after 48 h had a significantly higher risk of death or ventilation. CONCLUSION liver function test abnormalities are frequent among patients with COVID-19 and seasonal respiratory viruses, and are associated with poor clinical outcome. The late liver tests' peak had a twofold risk for adverse outcome. Though cholestatic injury was more common, hepatocellular injury had the greatest prognostic significance 48 h after admission. Our study may provide a viral specific auxiliary prognostic tool for clinicians facing patients with a respiratory virus.
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Affiliation(s)
- Einat Ritter
- Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel
| | - Eden Shusterman
- Department of Internal Medicine H, Tel Aviv Medical Center, 6 Weizmann St., Tel Aviv 64239, Israel
| | - Lior Prozan
- Department of Internal Medicine H, Tel Aviv Medical Center, 6 Weizmann St., Tel Aviv 64239, Israel
| | - Orli Kehat
- I-Medata AI Center, Tel Aviv Medical Center, 6 Weizmann St., Tel Aviv 64239, Israel
| | - Ahuva Weiss Meilik
- I-Medata AI Center, Tel Aviv Medical Center, 6 Weizmann St., Tel Aviv 64239, Israel
| | - Oren Shibolet
- Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel
| | - Jacob Nadav Ablin
- Department of Internal Medicine H, Tel Aviv Medical Center, 6 Weizmann St., Tel Aviv 64239, Israel
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Liatsos GD. SARS-CoV-2 induced liver injury: Incidence, risk factors, impact on COVID-19 severity and prognosis in different population groups. World J Gastroenterol 2023; 29:2397-2432. [PMID: 37179584 PMCID: PMC10167898 DOI: 10.3748/wjg.v29.i16.2397] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 02/17/2023] [Accepted: 04/07/2023] [Indexed: 04/24/2023] Open
Abstract
Liver is unlikely the key organ driving mortality in coronavirus disease 2019 (COVID-19) however, liver function tests (LFTs) abnormalities are widely observed mostly in moderate and severe cases. According to this review, the overall prevalence of abnormal LFTs in COVID-19 patients ranges from 2.5% to 96.8% worldwide. The geographical variability in the prevalence of underlying diseases is the determinant for the observed discrepancies between East and West. Multifactorial mechanisms are implicated in COVID-19-induced liver injury. Among them, hypercytokinemia with "bystander hepatitis", cytokine storm syndrome with subsequent oxidative stress and endotheliopathy, hypercoagulable state and immuno-thromboinflammation are the most determinant mechanisms leading to tissue injury. Liver hypoxia may also contribute under specific conditions, while direct hepatocyte injury is an emerging mechanism. Except for initially observed severe acute respiratory distress syndrome corona virus-2 (SARS-CoV-2) tropism for cholangiocytes, more recent cumulative data show SARS-CoV-2 virions within hepatocytes and sinusoidal endothelial cells using electron microscopy (EM). The best evidence for hepatocellular invasion by the virus is the identification of replicating SARS-CoV-2 RNA, S protein RNA and viral nucleocapsid protein within hepatocytes using in-situ hybridization and immunostaining with observed intrahepatic presence of SARS-CoV-2 by EM and by in-situ hybridization. New data mostly derived from imaging findings indicate possible long-term sequelae for the liver months after recovery, suggesting a post-COVID-19 persistent live injury.
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Affiliation(s)
- George D Liatsos
- Department of Internal Medicine, Hippokration General Hospital, Athens 11527, Attiki, Greece
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28
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de Lima IC, de Menezes DC, Uesugi JHE, Bichara CNC, da Costa Vasconcelos PF, Quaresma JAS, Falcão LFM. Liver Function in Patients with Long-Term Coronavirus Disease 2019 of up to 20 Months: A Cross-Sectional Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:5281. [PMID: 37047897 PMCID: PMC10094195 DOI: 10.3390/ijerph20075281] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 03/03/2023] [Accepted: 03/08/2023] [Indexed: 06/19/2023]
Abstract
The long-term laboratory aspects of the effects of coronavirus disease 2019 (COVID-19) on liver function are still not well understood. Therefore, this study aimed to evaluate the hepatic clinical laboratory profile of patients with up to 20 months of long-term COVID-19. A total of 243 patients of both sexes aged 18 years or older admitted during the acute phase of COVID-19 were included in this study. Liver function analysis was performed. Changes were identified in the mean levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), and ferritin. A ferritin level of >300 U/L was observed in the group that presented more changes in liver function markers (ALT, AST, and GGT). Age ≥ 60 years, male sex, AST level > 25 U/L, and GGT level ≥ 50 or 32 U/L were associated with an ALT level > 29 U/L. A correlation was found between ALT and AST, LDH, GGT, and ferritin. Our findings suggest that ALT and AST levels may be elevated in patients with long-term COVID-19, especially in those hospitalised during the acute phase. In addition, an ALT level > 29 U/L was associated with changes in the levels of other markers of liver injury, such as LDH, GGT, and ferritin.
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Affiliation(s)
- Igor Costa de Lima
- Center for Biological Health Sciences, State University of Pará, Belém 66087670, Brazil
| | | | | | | | | | - Juarez Antônio Simões Quaresma
- Center for Biological Health Sciences, State University of Pará, Belém 66087670, Brazil
- Tropical Medicine Center, Federal University of Pará, Belém 66055240, Brazil
- School of Medicine, São Paulo University, São Paulo 01246903, Brazil
| | - Luiz Fábio Magno Falcão
- Center for Biological Health Sciences, State University of Pará, Belém 66087670, Brazil
- School of Medicine, São Paulo University, São Paulo 01246903, Brazil
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Henrie J, Gerard L, Declerfayt C, Lejeune A, Baldin P, Robert A, Laterre PF, Hantson P. Profile of liver cholestatic biomarkers following prolonged ketamine administration in patients with COVID-19. BMC Anesthesiol 2023; 23:44. [PMID: 36750971 PMCID: PMC9902832 DOI: 10.1186/s12871-023-02006-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 02/02/2023] [Indexed: 02/09/2023] Open
Abstract
BACKGROUND To investigate the possible influence of prolonged ketamine (K) or esketamine (ESK) infusion on the profile of liver cholestatic biomarkers in patients with COVID-19 infection. METHODS A retrospective analysis was performed on 135 patients with COVID-19 related ARDS who received prolonged K or ESK infusion. They were compared to 15 COVID-19 ICU patients who did not receive K/ESK while being mechanically ventilated and 108 COVID-19 patients who did not receive mechanical ventilation nor K/ESK. The profile of the liver function tests was analysed in the groups. RESULTS Peak values of ALP, GGT and bilirubin were higher in the K/ESK group, but not for AST and ALT. Peak values of ALP were significantly higher among patients who underwent mechanical ventilation and who received K/ESK, compared with mechanically ventilated patients who did not receive K/ESK. There was a correlation between these peak values and the cumulative dose and duration of K/ESK therapy. CONCLUSIONS Based on the observations of biliary anomalies in chronic ketamine abusers, prolonged exposure to ketamine sedation during mechanical ventilation may also be involved, in addition to viral infection causing secondary sclerosing cholangitis. The safety of prolonged ketamine sedation on the biliary tract requires further investigations.
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Affiliation(s)
- Julie Henrie
- grid.7942.80000 0001 2294 713XDepartment of Intensive Care, Cliniques St-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200 Brussels, Belgium
| | - Ludovic Gerard
- grid.7942.80000 0001 2294 713XDepartment of Intensive Care, Cliniques St-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200 Brussels, Belgium
| | - Caroline Declerfayt
- grid.7942.80000 0001 2294 713XDepartment of Intensive Care, Cliniques St-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200 Brussels, Belgium
| | - Adrienne Lejeune
- grid.7942.80000 0001 2294 713XDepartment of Intensive Care, Cliniques St-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200 Brussels, Belgium
| | - Pamela Baldin
- grid.7942.80000 0001 2294 713XDepartment of Pathology, Cliniques St-Luc, Université Catholique de Louvain, 1200 Brussels, Belgium
| | - Arnaud Robert
- grid.7942.80000 0001 2294 713XDepartment of Intensive Care, Cliniques St-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200 Brussels, Belgium
| | - Pierre-François Laterre
- grid.7942.80000 0001 2294 713XDepartment of Intensive Care, Cliniques St-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200 Brussels, Belgium
| | - Philippe Hantson
- Department of Intensive Care, Cliniques St-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200, Brussels, Belgium. .,Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Université Catholique de Louvain, 1200, Brussels, Belgium.
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Abstract
The coronavirus disease-2019 (COVID-19) pandemic has had a large impact on patients with chronic liver disease (CLD) and liver transplantation (LT) recipients. Patients with advanced CLD are at a significantly increased risk of poor outcomes in the setting of severe acute respiratory syndrome coronavirus 2 infection. The pandemic has also considerably altered the management and care that is provided to patients with CLD, pre-LT patients, and LT recipients. Vaccination against COVID-19 protects patients with CLD and LT recipients from adverse outcomes and is safe in these patients; however, vaccine efficacy may be reduced in LT recipients and other immunosuppressed patients.
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Gupta T, Sharma H. COVID-19 and the liver: Are footprints still there? World J Gastroenterol 2023; 29:656-669. [PMID: 36742164 PMCID: PMC9896610 DOI: 10.3748/wjg.v29.i4.656] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 10/13/2022] [Accepted: 11/21/2022] [Indexed: 01/20/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) hit the entire world as a global pandemic and soon became the most important concern for all patients with chronic diseases. An early trend in higher mortality in patients with acute respiratory distress attracted all researchers to closely monitor patients for the involvement of other systems. It soon became apparent that patients with chronic liver diseases are at increased risk of mortality given their cirrhosis-associated immune dysfunction. Additionally, liver function abnormalities were noted in patients with severe COVID-19. Profound cytokine storm, direct viral infection, drugs and reactivation of viral infections were causes of deranged liver functions. Here, we discuss the relation between COVID-19 and chronic liver disease, specifically cirrhosis, hepatitis B, hepatitis C, and non-alcoholic fatty liver disease (NAFLD), as well as the liver manifestations of COVID-19. The metabolic syndrome, obesity, diabetes mellitus and NAFLD were found to worsen outcome in different studies reported worldwide. Decompensated cirrhosis should be considered a risk factor for death and severe COVID-19. Recently, COVID-19 related cholangiopathy has also been reported with changes of secondary sclerosing cholangitis. The long-term persistence of viral antigens in gut epithelia raises concern regarding the future risk of autoimmune liver diseases.
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Affiliation(s)
- Tarana Gupta
- Department of Medicine, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak 124001, Haryana, India
| | - Hemant Sharma
- Department of Medicine, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak 124001, Haryana, India
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Baldelli L, Marjot T, Barnes E, Barritt AS, Webb GJ, Moon AM. SARS-CoV-2 Infection and Liver Disease: A Review of Pathogenesis and Outcomes. Gut Liver 2023; 17:12-23. [PMID: 36457261 PMCID: PMC9840920 DOI: 10.5009/gnl220327] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/31/2022] [Accepted: 09/07/2022] [Indexed: 12/03/2022] Open
Abstract
The impact of the coronavirus disease 2019 (COVID-19) pandemic has been immense, and it continues to have lasting repercussions. While the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus primarily infects the respiratory system, other organ systems are affected, including the liver. Scientific knowledge on the role of SARS-CoV-2 infection and liver injury has evolved rapidly, with recent data suggesting specific hepatotropism of SARS-CoV-2. Moreover, additional concerns have been raised in regard to long-term liver damage, related to emerging cases of post-COVID-19 cholangiopathy and chronic cholestasis. Great effort has also been focused on studying how specific subpopulations with chronic medical conditions might be disproportionately impacted by COVID-19. One such population includes individuals with chronic liver disease (CLD) and cirrhosis, with an expanding body of research indicating these patients being particularly susceptible to adverse outcomes. In this review, we provide an updated summary on the current pathogenesis and mechanism of liver injury in the setting of SARS-CoV-2 infection, the association between health outcomes and SARS-CoV-2 infection in patients with CLD, and the unique consequences of the COVID-19 pandemic on the routine care of patients with CLD.
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Affiliation(s)
- Luke Baldelli
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
| | - Thomas Marjot
- Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, UK
| | - Eleanor Barnes
- Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, UK
| | - A. Sidney Barritt
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
| | - Gwilym J. Webb
- Cambridge Liver Unit, Addenbrooke's Hospital, Cambridge, UK
| | - Andrew M. Moon
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
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Brandi N, Spinelli D, Granito A, Tovoli F, Piscaglia F, Golfieri R, Renzulli M. COVID-19: Has the Liver Been Spared? Int J Mol Sci 2023; 24:1091. [PMID: 36674607 PMCID: PMC9866733 DOI: 10.3390/ijms24021091] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 01/03/2023] [Accepted: 01/04/2023] [Indexed: 01/09/2023] Open
Abstract
The liver is a secondary and often collateral target of COVID-19 disease but can lead to important consequences. COVID-19 might directly cause a high number of complications in patients with pre-existing chronic liver disease, increasing their risk of hepatic decompensation. Moreover, it also determines indirect consequences in the management of patients with liver disease, especially in those suffering from decompensated cirrhosis and HCC, as well as in the execution of their follow-up and the availability of all therapeutic possibilities. Liver imaging in COVID-19 patients proved to be highly nonspecific, but it can still be useful for identifying the complications that derive from the infection. Moreover, the recent implementation of telemedicine constitutes a possible solution to both the physical distancing and the re-organizational difficulties arising from the pandemic. The present review aims to encompass the currently hypothesized pathophysiological mechanisms of liver injury in patients with COVID-19 mediated by both the direct invasion of the virus and its indirect effects and analyze the consequence of the pandemic in patients with chronic liver disease and liver tumors, with particular regard to the management strategies that have been implemented to face this worldwide emergency and that can be further improved.
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Affiliation(s)
- Nicolò Brandi
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
| | - Daniele Spinelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
| | - Alessandro Granito
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Francesco Tovoli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Rita Golfieri
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
| | - Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
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Muacevic A, Adler JR, Tripathy S, Bhuniya S, Mangaraj M, Ramadass B, Sahu S, Bandyopadhyay D, Dash P, Saharia GK. Analysis of Biochemical and Inflammatory Markers for Predicting COVID-19 Severity: Insights From a Tertiary Healthcare Institution of Eastern India. Cureus 2023; 15:e33893. [PMID: 36819455 PMCID: PMC9934847 DOI: 10.7759/cureus.33893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/17/2023] [Indexed: 01/19/2023] Open
Abstract
Background Coronavirus disease-19 (COVID-19) patients often deteriorate rapidly based on viral infection-related inflammation and the subsequent cytokine storm. The clinical symptoms were found to be inconsistent with laboratory findings. There is a need to develop biochemical severity score to closely monitor COVID-19 patients. Methods This study was conducted in the department of biochemistry at All India Institute of Medical Sciences (AIIMS) Bhubaneswar in collaboration with the intensive care unit. Laboratory data of 7,395 patients diagnosed with COVID-19 during the first three waves of the pandemic were analyzed. The serum high sensitivity high-sensitivity C-reactive protein (hs-CRP, immuno-turbidity method), lactate dehydrogenase (LDH, modified Wacker et al. method), and liver enzymes (kinetic-UV method) were estimated by fully automated chemistry analyzer. Serum ferritin and interleukin-6 (IL-6) were measured by one-step immunoassay using chemiluminescence technology. Three models were used in logistic regression to check for the predictive potential of biochemical parameters, and a COVID-19 biochemical severity score was calculated using a non-linear regression algorithm. Results The receiver operating characteristic curve found age, urea, uric acid, CRP, ferritin, IL6, and LDH with the highest odds of predicting ICU admission for COVID-19 patients. COVID-19 biochemical severity scores higher than 0.775 were highly predictive (odds ratio of 5.925) of ICU admission (AUC=0.740, p<0.001) as compared to any other individual parameter. For the validation, 30% of the total dataset was used as testing data (n=2095) with a sensitivity of 68.3%, specificity of 74.5%, and odds ratio of 6.304. Conclusion Age, urea, uric acid, ferritin, IL6, LDH, and CRP-based predictive probability algorithm calculating COVID-19 severity was found to be highly predictive of ICU admission for COVID-19 patients.
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35
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Jia FJ, Han J. Liver injury in COVID-19: Holds ferritinophagy-mediated ferroptosis accountable. World J Clin Cases 2022; 10:13148-13156. [PMID: 36683648 PMCID: PMC9850986 DOI: 10.12998/wjcc.v10.i36.13148] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 11/20/2022] [Accepted: 12/08/2022] [Indexed: 12/26/2022] Open
Abstract
Even in patients without a history of liver disease, liver injury caused by coronavirus disease 2019 (COVID-19) is gradually becoming more common. However, the precise pathophysiological mechanisms behind COVID-19's liver pathogenicity are still not fully understood. We hypothesize that inflammation may become worse by cytokine storms caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Elevated ferritin levels can initiate ferritinophagy mediated by nuclear receptor coactivator 4 (NCOA4), which leads to iron elevation, and ferroptosis. In COVID-19 patients, ferroptosis can be restricted to reduce disease severity and liver damage by targeting NCOA4-mediated ferritinophagy. To confirm the role of ferritinophagy-mediated ferroptosis in SARS-CoV-2 infection, further research is required.
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Affiliation(s)
- Feng-Ju Jia
- School of Nursing, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Jing Han
- School of Nursing, Qingdao University, Qingdao 266071, Shandong Province, China
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36
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He YF, Jiang ZG, Wu N, Bian N, Ren JL. Correlation between COVID-19 and hepatitis B: A systematic review. World J Gastroenterol 2022; 28:6599-6618. [PMID: 36569273 PMCID: PMC9782843 DOI: 10.3748/wjg.v28.i46.6599] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Revised: 10/29/2022] [Accepted: 11/19/2022] [Indexed: 12/08/2022] Open
Abstract
BACKGROUND There is growing evidence that patients with coronavirus disease 2019 (COVID-19) frequently present with liver impairment. Hepatitis B virus (HBV) remains a major public health threat in current society. Both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and HBV can cause liver damage, and current findings on whether HBV infection increases disease severity in COVID-19 patients are inconsistent, and whether SARS-CoV-2 infection accelerates hepatitis B progression or leads to a worse prognosis in hepatitis B patients has not been adequately elucidated. AIM To explore the complex relationship between COVID-19 and hepatitis B in order to inform the research and management of patients co-infected with SARS-CoV-2 and HBV. METHODS An experienced information specialist searched the literature in the following online databases: PubMed, China National Knowledge Infrastructure, Google Scholar, Scopus, Wiley, Web of Science, Cochrane, and ScienceDirect. The literature published from December 2019 to September 1, 2022 was included in the search. We also searched medRxiv and bioRxiv for gray literature and manually scanned references of included articles. Articles reporting studies conducted in humans discussing hepatitis B and COVID-19 were included. We excluded duplicate publications. News reports, reports, and other gray literature were included if they contained quantifiable evidence (case reports, findings, and qualitative analysis). Some topics that included HBV or COVID-19 samples but did not have quantitative evidence were excluded from the review. RESULTS A total of 57 studies were eligible and included in this review. They were from 11 countries, of which 33 (57.9%) were from China. Forty-two of the 57 studies reported abnormalities in liver enzymes, three mainly reported abnormalities in blood parameters, four indicated no significant liver function alterations, and another eight studies did not provide data on changes in liver function. Fifty-seven studies were retrospective and the total number of co-infections was 1932, the largest sample size was 7723, and the largest number of co-infections was 353. Most of the studies suggested an interaction between hepatitis B and COVID-19, while 12 studies clearly indicated no interaction between hepatitis B and COVID-19. Six of the 57 studies clearly reported HBV activation. Six studies were related to liver transplant patients. CONCLUSION There is some association between COVID-19 and hepatitis B. Future high-quality randomized trials are needed to further elucidate the interaction between COVID-19 and hepatitis B.
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Affiliation(s)
- Yan-Fei He
- Health Management Center, The Sixth Medical Center, Chinese PLA General Hospital, Beijing 100048, China
| | - Zhi-Gang Jiang
- Department of Statistics, Zunyi Medical University, Guizhou 563006, Guizhou Province, China
| | - Ni Wu
- Health Management Center, The Sixth Medical Center, Chinese PLA General Hospital, Beijing 100048, China
| | - Ning Bian
- Health Management Center, The Sixth Medical Center, Chinese PLA General Hospital, Beijing 100048, China
| | - Jun-Lin Ren
- Department of Infection Control, The Sixth Medical Center, Chinese PLA General Hospital, Beijing 100048, China
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Global Hemostasis Potential in COVID-19 Positive Patients Performed on St-Genesia Show Hypercoagulable State. J Clin Med 2022; 11:jcm11247255. [PMID: 36555872 PMCID: PMC9785526 DOI: 10.3390/jcm11247255] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 12/02/2022] [Accepted: 12/05/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND At the dawn of the pandemic, severe forms of COVID-19 were often complicated by thromboembolisms. However, routine laboratory tests cannot be used to predict thromboembolic events. The objective of this study was to investigate the potential value of the thrombin generation test (TGT) in predicting hypercoagulability and thrombotic risk in the aforementioned set of patients. METHODS The study panel comprised 52 patients divided into two groups (26 COVID-19 positive and 26 COVID-19 negative); COVID-19-positive patients were further grouped in "severe" (n = 11) and "non-severe" (n = 15) categories based on clinical criteria. The routine blood tests and TGT of these patients were retrospectively analyzed. RESULTS All 26 COVID-19-positive patients showed decreased lymphocyte, monocyte and basophil counts and increased lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine transaminase (ALT) compared with control patients. Conversely, we did not observe statistically significant differences between severe and non-severe patients despite anecdotal variations in the distribution patterns. TGT without thrombomodulin (TM) addition showed statistically significant differences in the thrombin peak heights between COVID-19-positive and negative patients. After addition of TM, peak height, Endogenous Thrombin Potential (ETP) and velocity index were increased in all COVID-19-positive patients while the percentage of inhibition of ETP was reduced. These trends correlated with the severity of disease, showing a greater increase in peak height, ETP, velocity index and a drastic reduction in the percentage of ETP inhibition in more severely affected patients. CONCLUSIONS Our data suggest that all COVID-19 patients harbor a hypercoagulable TGT profile and that this is further pronounced in severely affected patients.
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Elghannam MT, Hassanien MH, Ameen YA, ELattar GM, ELRay AA, Turky EA, ELTalkawy MD. COVID-19 and liver diseases. EGYPTIAN LIVER JOURNAL 2022; 12:43. [PMID: 35880136 PMCID: PMC9301896 DOI: 10.1186/s43066-022-00202-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 07/06/2022] [Indexed: 12/15/2022] Open
Abstract
Coronavirus causes an outbreak of viral pneumonia that spread throughout the world. Liver injury is becoming more widely recognized as a component of the clinical picture of COVID-19 infection. Hepatitis with serum ALT elevation has been reported in up to half of patients. Patients with CLD were at a higher risk of decompensation with liver failure, hospitalization, and mortality. The percentage of acute liver injury (ALI) varied from 5 to 28%. COVID-19 hinders HCV elimination by 2030. It is recommended to continue treatment of chronic HCV and chronic HBV if already receiving treatment. Consider using antiviral therapy to prevent viral flare-ups in patients with occult or resolved HBV and COVID-19 who are receiving immunosuppressive agents. Patients with AIH do not have an increased risk of adverse outcomes even in high-risk areas. There is an association between MAFLD and disease progression. Patients with any type of cancer are at a higher risk of infection and are more likely to develop more severe clinical outcomes. Most societies advise against immunosuppressant modifications in patients with mild COVID-19, whereas in rare cases such as severe lymphopenia, worsening pneumonia, or bacterial or fungal superinfection, reduction or discontinuation of antiproliferative agents and lymphocyte-depleting therapies has been suggested.
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Ferreira FB, Mourato M, Bragança S, Paulo JB, Sismeiro R, Pereira A, Mónica AN, Lourenço LC, Cardoso M. COVID-19-associated secondary sclerosing cholangitis - A case series of 4 patients. Clin Res Hepatol Gastroenterol 2022; 46:102048. [PMID: 36347499 PMCID: PMC9636600 DOI: 10.1016/j.clinre.2022.102048] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 10/24/2022] [Accepted: 11/03/2022] [Indexed: 11/08/2022]
Abstract
We report a case series of four patients diagnosed with COVID-19-associated secondary sclerosing cholangitis (SSC), a recently described rare late complication of severe COVID-19. Following prolonged stays in the intensive care unit, these patients developed marked sustained cholestasis and jaundice despite clinical improvement. Cholangiography showed beaded appearance of intra-hepatic bile ducts and bile casts were removed in one patient. None of the patients reached normalization of liver enzymes and at least one progressed to liver cirrhosis (follow-up time of 11 to 16 months). COVID-19-associated SSC has a dismal prognosis with rapid progression to advanced chronic liver disease.
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Affiliation(s)
- Filipa Bordalo Ferreira
- Gastroenterology department, Hospital Professor Doutor Fernando Fonseca, IC 19, 2720-276 Amadora, Portugal.
| | - Margarida Mourato
- Internal Medicine department, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal, IC 19, 2720-276 Amadora, Portugal
| | - Sofia Bragança
- Gastroenterology department, Hospital Professor Doutor Fernando Fonseca, IC 19, 2720-276 Amadora, Portugal
| | - Joana Batista Paulo
- Internal Medicine department, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal, IC 19, 2720-276 Amadora, Portugal
| | - Rita Sismeiro
- Internal Medicine department, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal, IC 19, 2720-276 Amadora, Portugal
| | - André Pereira
- Pathology department, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal, IC 19, 2720-276 Amadora, Portugal
| | - Ana Nassauer Mónica
- Radiology department, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal. IC 19, 2720-276 Amadora, Portugal
| | - Luís Carvalho Lourenço
- Gastroenterology department, Hospital Professor Doutor Fernando Fonseca, IC 19, 2720-276 Amadora, Portugal
| | - Mariana Cardoso
- Gastroenterology department, Hospital Professor Doutor Fernando Fonseca, IC 19, 2720-276 Amadora, Portugal
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Li X, Wang W, Yan S, Zhao W, Xiong H, Bao C, Chen J, Yue Y, Su Y, Zhang C. Drug-induced liver injury in COVID-19 treatment: Incidence, mechanisms and clinical management. Front Pharmacol 2022; 13:1019487. [PMID: 36518661 PMCID: PMC9742434 DOI: 10.3389/fphar.2022.1019487] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 11/14/2022] [Indexed: 07/21/2023] Open
Abstract
The COVID-19 outbreak triggered a serious and potentially lethal pandemic, resulting in massive health and economic losses worldwide. The most common clinical manifestations of COVID-19 patients are pneumonia and acute respiratory distress syndrome, with a variety of complications. Multiple organ failure and damage, ultimately leading to patient death, are possible as a result of medication combinations, and this is exemplified by DILI. We hope to summarize DILI caused by the antiviral drugs favipiravir, remdesivir, lopinavir/ritonavir, and hydroxychloroquine in COVID-19 patients in this review. The incidence of liver injury in the treatment of COVID-19 patients was searched on PubMed to investigate DILI cases. The cumulative prevalence of acute liver injury was 23.7% (16.1%-33.1%). We discuss the frequency of these events, potential mechanisms, and new insights into surveillance strategies. Furthermore, we also describe medication recommendations aimed at preserving DILI caused by treatment in COVID-19 patients.
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Affiliation(s)
- Xichuan Li
- Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin, China
| | - Wanting Wang
- Department of Colorectal Surgery, Tianjin Institute of Coloproctology, The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Suying Yan
- Department of Colorectal Surgery, Tianjin Institute of Coloproctology, The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Weipeng Zhao
- Department of Breast Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China
| | - Hui Xiong
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China
| | - Cuiping Bao
- Departments of Radiology, Tianjin Union Medical Center, Tianjin, China
| | - Jinqian Chen
- Departments of Pharmacy, NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital, Tianjin, China
| | - Yuan Yue
- Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin, China
| | - Yanjun Su
- Department of Lung Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China
| | - Chunze Zhang
- Department of Colorectal Surgery, Tianjin Institute of Coloproctology, The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China
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Yu SY, Xie JR, Luo JJ, Lu HP, Xu L, Wang JJ, Chen XQ. Liver test abnormalities in asymptomatic and mild COVID-19 patients and their association with viral shedding time. World J Hepatol 2022; 14:1953-1963. [PMID: 36483605 PMCID: PMC9724107 DOI: 10.4254/wjh.v14.i11.1953] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Revised: 10/25/2022] [Accepted: 11/21/2022] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Asymptomatic infections and mild symptoms are common in patients infected with the Omicron variant, and data on liver test abnormalities are rare.
AIM To evaluated the clinical characteristics of asymptomatic and mild coronavirus disease 2019 (COVID-19) patients with abnormal liver test results.
METHODS This retrospective study included 661 laboratory-confirmed asymptomatic and mild COVID-19 patients who were treated in two makeshift hospitals in Ningbo from April 5, 2022 to April 29, 2022. Clinical information and viral shedding time were collected, and univariate and multivariate logistic regression models were performed in statistical analyses.
RESULTS Of the 661 patients, 83 (12.6%) had liver test abnormalities, and 6 (0.9%) had liver injuries. Abnormal liver tests revealed a reliable correlation with a history of liver disease (P < 0.001) and a potential correlation with male sex and obesity (P < 0.05). Elevated alanine aminotransferase was reliably associated with obesity (P < 0.05) and a history of liver disease (P < 0.001). Elevated aspartate transaminase (AST) was reliably correlated with a history of liver disease (P < 0.001), and potentially correlated with age over 30 years (P < 0.05). There was a reliable correlation between AST ≥ 2× the upper limit of normal and a longer viral shedding time, especially in mild cases.
CONCLUSION Obesity and a history of liver disease are risk factors for liver test abnormalities. Being male and an older age are potential risk factors. Attention should be given to liver tests in asymptomatic and mild COVID-19 patients, which has crucial clinical significance for evaluating the viral shedding time.
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Affiliation(s)
- Si-Yi Yu
- Department of Gastroenterology, Ningbo First Hospital, Ningbo 315010, Zhejiang Province, China
| | - Jia-Rong Xie
- Department of Gastroenterology, Ningbo First Hospital, Ningbo 315010, Zhejiang Province, China
| | - Jun-Jun Luo
- Department of Cardiology, Ningbo First Hospital, Ningbo 315010, Zhejiang Province, China
| | - Hong-Peng Lu
- Department of Gastroenterology, Ningbo First Hospital, Ningbo 315010, Zhejiang Province, China
| | - Lei Xu
- Department of Gastroenterology, Ningbo First Hospital, Ningbo 315010, Zhejiang Province, China
| | - Jun-Jie Wang
- Department of Information Technology, Ningbo First Hospital, Ningbo 315010, Zhejiang Province, China
| | - Xue-Qin Chen
- Department of Traditional Medicine, Ningbo First Hospital, Ningbo 315010, Zhejiang Province, China
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Grando M, Balbi M, Zeppieri M. COVID-19-induced liver injury in adult patients: A brief overview. World J Virol 2022; 11:443-452. [PMID: 36483102 PMCID: PMC9724208 DOI: 10.5501/wjv.v11.i6.443] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/07/2022] [Accepted: 10/12/2022] [Indexed: 11/23/2022] Open
Abstract
Coronavirus disease has spread worldwide since 2019, causing important pandemic issues and various social health problems to date. Little is known about the origin of this virus and the effects it has on extra-pulmonary organs. The different mechanisms of the virus and the influence it has on humans are still being studied, with hopes of finding a cure for the disease and the pathologies associated with the infection. Liver damage caused by coronavirus disease 2019 (COVID-19) is sometimes underestimated and has been of important clinical interest in the past few years. Hepatic dysfunctions can manifest in different forms which can sometimes be mild and without specific signs and symptoms or be severe with important clinical implications. There are several studies that have tried to explain the mechanism of entry (hepatotropism) of the virus into hepatocytes and the effects the virus has on this important organ. What clearly emerges from the current literature is that hepatic injury represents an important clinical aspect in the management of patients infected with COVID-19, especially in frail patients and those with comorbidities. The aim of our brief overview is to summarize the current literature regarding the forms of hepatic damage, complications, mechanisms of pathology, clinical features of liver injury, influence of comorbidities and clinical management in patients with COVID-19 infection.
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Affiliation(s)
- Martina Grando
- Department of Internal Medicine, Azienda Sanitaria Friuli Occidentale, San Vito al Tagliamento 33078, Italy
| | - Massimiliano Balbi
- Department of Internal Medicine, Azienda Sanitaria Friuli Occidentale, San Vito al Tagliamento 33078, Italy
| | - Marco Zeppieri
- Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy
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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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Liu X, Tian X, Ma Z, Chen J, Huang Q, Gao P, Zhang C. Efficacy and safety of glycyrrhizic acid preparation treating comorbid liver injury in COVID-19: A systematic review. Front Pharmacol 2022; 13:1003697. [PMID: 36408213 PMCID: PMC9669476 DOI: 10.3389/fphar.2022.1003697] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 10/18/2022] [Indexed: 10/12/2023] Open
Abstract
Background: No specific drug for COVID-19 has been found, and many studies have found that different degrees of liver injury often occurred after infection with COVID-19. Glycyrrhizic acid preparation (GAP) has been frequently used clinically, often combined with conventional treatments such as antiviral therapy, to improve the prognosis of COVID-19 and patients' liver function. Aims: To critically review and analyze clinical evidence on the efficacy and safety of GAP in the treatment of COVID-19 alone and COVID-19 with comorbid liver injury. Methods: A systematic literature review was performed following a sensitive searching strategy that examines all articles published in "WHO COVID-19 Research Database," "Cochrane Library," "VIP," "CNKI," "Wanfang," and "CBM" from 2020 to July 2022. Articles were evaluated by peer reviewers and used Joanna Briggs Institute (JBI) critical appraisal tools to complete the assessment of the risk of bias. Results: Ten clinical studies were finally included, involving 598 patients with COVID-19, of whom 189 were confirmed to be with comorbid liver injury. The main GAPs used are diammonium glycyrrhizinate and magnesium isoglycyrrhizinate, which have shown efficacy in improving liver function, inhibiting inflammation, and enhancing immunity. We are still seeking more related research. Conclusion: Glycyrrhizic acid preparations (mainly diammonium glycyrrhizinate and magnesium isoglycyrrhizinate) have a considerable clinical effect on improving liver function in patients with COVID-19 alone or with comorbid liver injury. Further studies on the use of GAP in the treatment of COVID-19 with comorbid liver injury and its mechanism are still needed. Systematic Review Registration: [www.crd.york.ac.uk/prospero], identifier [CRD42021234647].
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Affiliation(s)
- Xu Liu
- Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xia Tian
- Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Zhipeng Ma
- Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jiali Chen
- Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qingsong Huang
- Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Peiyang Gao
- Department of Critical Care Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Chuantao Zhang
- Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Thandassery RB, Dranoff JA, Perisetti A, Taddei T. COVID-19 and the liver: a narrative review of the present state of knowledge. Transl Gastroenterol Hepatol 2022; 7:40. [PMID: 36300154 PMCID: PMC9468988 DOI: 10.21037/tgh-20-243] [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: 06/09/2020] [Accepted: 09/22/2020] [Indexed: 11/30/2022] Open
Abstract
Novel corona virus disease (COVID-19) is an ongoing pandemic that has spread across the globe. The virus primarily infects type-2 pneumocytes in alveoli and causes lung disease, with severity ranging from mild pneumonia to acute respiratory distress syndrome. The virus also invades gastrointestinal epithelial cells, hepatocytes, and biliary epithelial cells. Derangement of liver function tests is noted in about one third of patients and appears to correlate with more severe disease. There are multiple mechanisms by which the virus can cause liver injury; immune-mediated inflammation and direct viral cytotoxicity are believed to be the predominant mechanisms. Liver injury appears to be transient, usually recovering with resolution of illness. Limited available studies and experience from prior corona virus pandemics seem to suggest that immunosuppressed patients have similar outcomes compared to non-immunosuppressed patients. Age and comorbid conditions seem to influence outcome, irrespective of immune status. Additionally, patients with preexisting comorbid conditions are more prone to acquire infection and should strictly adhere to travel and social distancing advisories. Telemedicine should be utilized to provide uninterrupted care for patients with liver disease, and clinic or hospital visits should be advised only in sick patients with advanced liver disease. In conclusion, liver dysfunction is not uncommon in COVID-19, it generally improves with resolution of disease, and patients with chronic liver disease (CLD) need continued follow up, uninterrupted by the ongoing pandemic, preferably in virtual clinic settings.
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Affiliation(s)
- Ragesh B. Thandassery
- Division of Gastroenterology, Department of Medicine, Central Arkansas Veteran Healthcare System, Little Rock, AR, USA
- Division of Gastroenterology, Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Jonathan A. Dranoff
- Division of Gastroenterology, Department of Medicine, Central Arkansas Veteran Healthcare System, Little Rock, AR, USA
- Division of Gastroenterology, Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Abhilash Perisetti
- Division of Gastroenterology, Department of Medicine, Central Arkansas Veteran Healthcare System, Little Rock, AR, USA
- Division of Gastroenterology, Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Tamar Taddei
- Section of Digestive Diseases, Department of Medicine, VA Connecticut Healthcare System, New Haven, CT, USA
- Section of Digestive Diseases, Department of Medicine, Yale School of Medicine, Yale University, New Haven, CT, USA
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Liakina V, Stundiene I, Milaknyte G, Bytautiene R, Reivytyte R, Puronaite R, Urbanoviciute G, Kazenaite E. Effects of COVID-19 on the liver: The experience of a single center. World J Gastroenterol 2022; 28:5735-5749. [PMID: 36338891 PMCID: PMC9627423 DOI: 10.3748/wjg.v28.i39.5735] [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: 06/22/2022] [Revised: 08/12/2022] [Accepted: 09/21/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The coronavirus disease 2019 (COVID-19) was perhaps the most severe global health crisis in living memory. Alongside respiratory symptoms, elevated liver enzymes, abnormal liver function, and even acute liver failure were reported in patients suffering from severe acute respiratory disease coronavirus 2 pneumonia. However, the precise triggers of these forms of liver damage and how they affect the course and outcomes of COVID-19 itself remain unclear. AIM To analyze the impact of liver enzyme abnormalities on the severity and outcomes of COVID-19 in hospitalized patients. METHODS In this study, 684 depersonalized medical records from patients hospitalized with COVID-19 during the 2020-2021 period were analyzed. COVID-19 was diagnosed according to the guidelines of the National Institutes of Health (2021). Patients were assigned to two groups: those with elevated liver enzymes (Group 1: 603 patients), where at least one out of four liver enzymes were elevated (following the norm of hospital laboratory tests: alanine aminotransferase (ALT) ≥ 40, aspartate aminotransferase (AST) ≥ 40, gamma-glutamyl transferase ≥ 36, or alkaline phosphatase ≥ 150) at any point of hospitalization, from admission to discharge; and the control group (Group 2: 81 patients), with normal liver enzymes during hospitalization. COVID-19 severity was assessed according to the interim World Health Organization guidance (2022). Data on viral pneumonia complications, laboratory tests, and underlying diseases were also collected and analyzed. RESULTS In total, 603 (88.2%) patients produced abnormal liver test results. ALT and AST levels were elevated by a factor of less than 3 in 54.9% and 74.8% of cases with increased enzyme levels, respectively. Patients in Group 1 had almost double the chance of bacterial viral pneumonia complications [odds ratio (OR) = 1.73, P = 0.0217], required oxygen supply more often, and displayed higher biochemical inflammation indices than those in Group 2. No differences in other COVID-19 complications or underlying diseases were observed between groups. Preexisting hepatitis of a different etiology was rarely documented (in only 3.5% of patients), and had no impact on the severity of COVID-19. Only 5 (0.73%) patients experienced acute liver failure, 4 of whom died. Overall, the majority of the deceased patients (17 out of 20) had elevated liver enzymes, and most were male. All deceased patients had at least one underlying disease or combination thereof, and the deceased suffered significantly more often from heart diseases, hypertension, and urinary tract infections than those who made recoveries. Alongside male gender (OR = 1.72, P = 0.0161) and older age (OR = 1.02, P = 0.0234), diabetes (OR = 3.22, P = 0.0016) and hyperlipidemia (OR = 2.67, P = 0.0238), but not obesity, were confirmed as independent factors associated with more a severe COVID-19 infection in our cohort. CONCLUSION In our study, the presence of liver impairment allows us to predict a more severe inflammation with a higher risk of bacterial complication and worse outcomes of COVID-19. Therefore, patients with severe disease forms should have their liver tests monitored regularly and their results should be considered when selecting treatment to avoid further liver damage or even insufficiency.
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Affiliation(s)
- Valentina Liakina
- Centre of Hepatology, Gastroenterology and Dietetics, Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
- Department of Chemistry and Bioengineering, Faculty of Fundamental Sciences, VILNIUS TECH, Vilnius 10223, Lithuania
| | - Ieva Stundiene
- Centre of Hepatology, Gastroenterology and Dietetics, Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Gabriele Milaknyte
- Centre of Hepatology, Gastroenterology and Dietetics, Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Ramune Bytautiene
- Centre of Hepatology, Gastroenterology and Dietetics, Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Rosita Reivytyte
- Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Roma Puronaite
- Clinic of Cardiac and Vascular Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
- Institute of Data Science and Digital Technologies, Faculty of Mathematics and Informatics, Vilnius University, Vilnius 01513, Lithuania
| | | | - Edita Kazenaite
- Centre of Hepatology, Gastroenterology and Dietetics, Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
- Department of Pathology, Forensic Medicine and Pharmacology, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
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Pál K, Molnar AA, Huțanu A, Szederjesi J, Branea I, Timár Á, Dobreanu M. Inflammatory Biomarkers Associated with In-Hospital Mortality in Critical COVID-19 Patients. Int J Mol Sci 2022; 23:ijms231810423. [PMID: 36142336 PMCID: PMC9499352 DOI: 10.3390/ijms231810423] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/02/2022] [Accepted: 09/06/2022] [Indexed: 01/08/2023] Open
Abstract
The COVID-19 pandemic poses global healthcare challenges due to its unpredictable clinical course. The aim of this study is to identify inflammatory biomarkers and other routine laboratory parameters associated with in-hospital mortality in critical COVID-19 patients. We performed a retrospective observational study on 117 critical COVID-19 patients. Following descriptive statistical analysis of the survivor and non-survivor groups, optimal cut-off levels for the statistically significant parameters were determined using the ROC method, and the corresponding Kaplan-Meier survival curves were calculated. The inflammatory parameters that present statistically significant differences between survivors and non-survivors are IL-6 (p = 0.0004, cut-off = 27.68 pg/mL), CRP (p = 0.027, cut-off = 68.15 mg/L) and IL-6/Ly ratio (p = 0.0003, cut-off = 50.39). Additionally, other statistically significant markers are creatinine (p = 0.031, cut-off = 0.83 mg/dL), urea (p = 0.0002, cut-off = 55.85 mg/dL), AST (p = 0.0209, cut-off = 44.15 U/L), INR (p = 0.0055, cut-off = 1.075), WBC (p = 0.0223, cut-off = 11.68 × 109/L) and pH (p = 0.0055, cut-off = 7.455). A survival analysis demonstrated significantly higher in-hospital mortality rates of patients with values of IL-6, IL-6/Ly, AST, INR, and pH exceeding previously mentioned thresholds. In our study, IL-6 and IL-6/Ly have a predictive value for the mortality of critically-ill patients diagnosed with COVID-19. The integration of these parameters with AST, INR and pH could contribute to a prognostic score for the risk stratification of critical patients, reducing healthcare costs and facilitating clinical decision-making.
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Affiliation(s)
- Krisztina Pál
- Department of Laboratory Medicine, Emergency Clinical County Hospital, 540136 Targu Mures, Romania
- M2 Department, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania
| | - Anca Alexandra Molnar
- Department of Laboratory Medicine, Emergency Clinical County Hospital, 540136 Targu Mures, Romania
- M2 Department, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania
| | - Adina Huțanu
- Department of Laboratory Medicine, Emergency Clinical County Hospital, 540136 Targu Mures, Romania
- Department of Laboratory Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania
- Correspondence:
| | - János Szederjesi
- Department of Anesthesiology and Intensive Care, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania
- Department of Anesthesiology and Intensive Care, Emergency Clinical County Hospital, 540136 Targu Mures, Romania
| | - Ionuț Branea
- Department of Anesthesiology and Intensive Care, Emergency Clinical County Hospital, 540136 Targu Mures, Romania
| | - Ágota Timár
- Department of Anesthesiology and Intensive Care, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania
- Department of Anesthesiology and Intensive Care, Emergency Clinical County Hospital, 540136 Targu Mures, Romania
| | - Minodora Dobreanu
- Department of Laboratory Medicine, Emergency Clinical County Hospital, 540136 Targu Mures, Romania
- Department of Laboratory Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania
- Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540136 Targu Mures, Romania
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Anderson MA, Khauli MA, Goiffon RJ, Kambadakone A. Coronavirus Disease in the Abdomen. ADVANCES IN CLINICAL RADIOLOGY 2022; 4:25-35. [PMID: 37521427 PMCID: PMC9473699 DOI: 10.1016/j.yacr.2022.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Numerous abdominal manifestations have been reported in patients with coronavirus disease 2019 (COVID-19), including involvement of the luminal gastrointestinal (GI) tract, hepatobiliary system, pancreas, kidneys, spleen, and blood vessels. Although most of the associated radiological abnormalities are nonspecific without distinguishing imaging features to suggest COVID-19, unique presentations such as findings of bowel ischemia preceding gross findings of bowel necrosis have been reported. Awareness of the spectrum of abdominal manifestations of COVID-19 allows radiologists to optimize their search pattern and to raise the possibility of this etiology when appropriate. Awareness of the possible abdominal manifestations of COVID-19 should enhance detection by radiologists and improve patient care. This review provides a comprehensive overview with illustrative imaging examples of COVID-19 in the abdomen.
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Affiliation(s)
- Mark A Anderson
- Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, White Building, Room 270, Boston, MA 02114, USA
| | - Mark A Khauli
- Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, White Building, Room 270, Boston, MA 02114, USA
| | - Reece J Goiffon
- Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, White Building, Room 270, Boston, MA 02114, USA
| | - Avinash Kambadakone
- Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, White Building, Room 270, Boston, MA 02114, USA
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A linear relationship between De Ritis ratio and mortality in hospitalized patients with COVID-19: A secondary analysis based on a large retrospective cohort study. ILIVER 2022. [PMCID: PMC9424126 DOI: 10.1016/j.iliver.2022.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
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Tokarczyk U, Kaliszewski K, Kopszak A, Nowak Ł, Sutkowska-Stępień K, Sroczyński M, Sępek M, Dudek A, Diakowska D, Trocha M, Gajecki D, Gawryś J, Matys T, Maciejiczek J, Kozub V, Szalast R, Madziarski M, Zubkiewicz-Zarębska A, Letachowicz K, Kiliś-Pstrusińska K, Matera-Witkiewicz A, Pomorski M, Protasiewicz M, Sokołowski J, Adamik B, Kujawa K, Doroszko A, Madziarska K, Jankowska EA. Liver Function Tests in COVID-19: Assessment of the Actual Prognostic Value. J Clin Med 2022; 11:jcm11154490. [PMID: 35956107 PMCID: PMC9369475 DOI: 10.3390/jcm11154490] [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: 04/04/2022] [Revised: 07/28/2022] [Accepted: 07/29/2022] [Indexed: 01/08/2023] Open
Abstract
Deviations in laboratory tests assessing liver function in patients with COVID-19 are frequently observed. Their importance and pathogenesis are still debated. In our retrospective study, we analyzed liver-related parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), total bilirubin (TBIL), albumin, comorbidities and other selected potential risk factors in patients admitted with SARS-CoV-2 infection to assess their prognostic value for intensive care unit admission, mechanical ventilation necessity and mortality. We compared the prognostic effectiveness of these parameters separately and in pairs to the neutrophil-to-lymphocyte ratio (NLR) as an independent risk factor of in-hospital mortality, using the Akaike Information Criterion (AIC). Data were collected from 2109 included patients. We created models using a sample with complete laboratory tests n = 401 and then applied them to the whole studied group excluding patients with missing singular variables. We estimated that albumin may be a better predictor of the COVID-19-severity course compared to NLR, irrespective of comorbidities (p < 0.001). Additionally, we determined that hypoalbuminemia in combination with AST (OR 1.003, p = 0.008) or TBIL (OR 1.657, p = 0.001) creates excellent prediction models for in-hospital mortality. In conclusion, the early evaluation of albumin levels and liver-related parameters may be indispensable tools for the early assessment of the clinical course of patients with COVID-19.
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Affiliation(s)
- Urszula Tokarczyk
- Clinical Department of General, Minimally Invasive and Endocrine Surgery, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland; (K.S.-S.); (M.S.); (M.S.); (A.D.)
- Correspondence: (U.T.); (K.K.); Tel.: +48-723-781-491 (U.T.); +48-71-734-30-00 (K.K.); Fax: +48-71-734-30-00 (K.K.)
| | - Krzysztof Kaliszewski
- Clinical Department of General, Minimally Invasive and Endocrine Surgery, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland; (K.S.-S.); (M.S.); (M.S.); (A.D.)
- Correspondence: (U.T.); (K.K.); Tel.: +48-723-781-491 (U.T.); +48-71-734-30-00 (K.K.); Fax: +48-71-734-30-00 (K.K.)
| | - Anna Kopszak
- Statistical Analysis Center, Wroclaw Medical University, Marcinkowski Street 2-6, 50-368 Wroclaw, Poland; (A.K.); (K.K.)
| | - Łukasz Nowak
- Clinical Department of Urology and Urological Oncology, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland;
| | - Karolina Sutkowska-Stępień
- Clinical Department of General, Minimally Invasive and Endocrine Surgery, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland; (K.S.-S.); (M.S.); (M.S.); (A.D.)
| | - Maciej Sroczyński
- Clinical Department of General, Minimally Invasive and Endocrine Surgery, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland; (K.S.-S.); (M.S.); (M.S.); (A.D.)
| | - Monika Sępek
- Clinical Department of General, Minimally Invasive and Endocrine Surgery, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland; (K.S.-S.); (M.S.); (M.S.); (A.D.)
| | - Agata Dudek
- Clinical Department of General, Minimally Invasive and Endocrine Surgery, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland; (K.S.-S.); (M.S.); (M.S.); (A.D.)
| | - Dorota Diakowska
- Department of Basic Science, Faculty of Health Science, Wroclaw Medical University, Bartel Street 5, 51-618 Wroclaw, Poland;
| | - Małgorzata Trocha
- Department of Pharmacology, Wroclaw Medical University, Mikulicz-Radecki Street 2, 50-345 Wroclaw, Poland;
| | - Damian Gajecki
- Clinical Department of Internal and Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (D.G.); (J.G.); (T.M.); (A.D.)
| | - Jakub Gawryś
- Clinical Department of Internal and Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (D.G.); (J.G.); (T.M.); (A.D.)
| | - Tomasz Matys
- Clinical Department of Internal and Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (D.G.); (J.G.); (T.M.); (A.D.)
| | - Justyna Maciejiczek
- Clinical Department of Internal Medicine, Pneumology and Allergology, Wroclaw Medical University, M. Skłodowskiej-Curie Street 66, 50-369 Wroclaw, Poland; (J.M.); (V.K.); (R.S.)
| | - Valeriia Kozub
- Clinical Department of Internal Medicine, Pneumology and Allergology, Wroclaw Medical University, M. Skłodowskiej-Curie Street 66, 50-369 Wroclaw, Poland; (J.M.); (V.K.); (R.S.)
| | - Roman Szalast
- Clinical Department of Internal Medicine, Pneumology and Allergology, Wroclaw Medical University, M. Skłodowskiej-Curie Street 66, 50-369 Wroclaw, Poland; (J.M.); (V.K.); (R.S.)
| | - Marcin Madziarski
- Clinical Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland;
| | - Anna Zubkiewicz-Zarębska
- Clinical Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland;
| | - Krzysztof Letachowicz
- Clinical Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland; (K.L.); (K.M.)
| | - Katarzyna Kiliś-Pstrusińska
- Clinical Department of Pediatric Nephrology, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland;
| | - Agnieszka Matera-Witkiewicz
- Screening Laboratory of Biological Activity Assays and Collection of Biological Material, Faculty of Pharmacy, Wroclaw Medical University, Borowska Street 211A, 50-556 Wroclaw, Poland;
| | - Michał Pomorski
- Clinical Department of Gynecology and Obstetrics, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland;
| | - Marcin Protasiewicz
- Clinical Department and Clinic of Cardiology, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland;
| | - Janusz Sokołowski
- Department of Emergency Medicine, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland;
| | - Barbara Adamik
- Clinical Department of Anaesthesiology and Intensive Therapy, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland;
| | - Krzysztof Kujawa
- Statistical Analysis Center, Wroclaw Medical University, Marcinkowski Street 2-6, 50-368 Wroclaw, Poland; (A.K.); (K.K.)
| | - Adrian Doroszko
- Clinical Department of Internal and Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (D.G.); (J.G.); (T.M.); (A.D.)
| | - Katarzyna Madziarska
- Clinical Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland; (K.L.); (K.M.)
| | - Ewa Anita Jankowska
- University Hospital in Wroclaw, Institute of Heart Diseases, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland;
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