|
1
|
Kakavand G, Arabzadeh S, Mohebbi S, Saeedfar K, Abedini A, Mardani M. Impact of remdesivir treatment on factor VIII gene expression and hematological parameters in COVID-19 patients. Microb Pathog 2025; 204:107536. [PMID: 40187577 DOI: 10.1016/j.micpath.2025.107536] [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: 09/28/2024] [Revised: 03/27/2025] [Accepted: 04/02/2025] [Indexed: 04/07/2025]
Abstract
The novel coronavirus, COVID-19, which was first identified in December 2019 rapidly spread worldwide and was declared a global pandemic. Beyond respiratory symptoms, COVID-19 often results in coagulation and vascular endothelium disorders, causing increased clotting and bleeding, which are closely linked to the acute phase of the infection. Factor VIII is a crucial protein in the blood coagulation cascade, and elevated FVIII levels have been linked to thrombotic events in COVID-19, highlighting the need to understand its behavior during treatment. Remdesivir is an antiviral drug that has shown promise in reducing recovery time and mortality rates in COVID-19 patients. This study aims to examine the changes in blood factors and the expression of the factor VIII gene in patients treated with Remdesivir. Blood samples were collected from 30 COVID-19 patients before and after Remdesivir treatment and from 20 healthy individuals. Patients with underlying diseases were excluded from the study. RNA was extracted from these samples, followed by cDNA synthesis. The expression of the factor VIII gene was analyzed using Real-Time PCR. The results indicated that blood factors such as Urea, ALK, AST, WBC, and CRP were elevated in the patient group compared to the control group. At the same time, FBS, Urea, ALK, AST, WBC, RDW, INR, and K levels increased in the Remdesivir treatment group (P < 0.001). Conversely, MCHC, RBC, and Ca levels decreased in both patient and treatment groups compared to the control group (P < 0.001). The expression of the FVIII gene was upregulated approaching 2 times in COVID-19 patients and 1.5-fold in the treatment group compared to the control group (P < 0.001). However, no significant changes were observed in FVIII expression before and after Remdesivir treatment. However, a positive correlation between RBC, FBS, and Urea in the patient group and a negative correlation between RDW and FVIII expression levels was observed. In the treatment group, FVIII expression level correlated negatively with Urea, P, and RDW. These findings suggest that elevated FVIII levels are associated with disease severity and excessive coagulation in COVID-19 patients. Additionally, Remdesivir does not appear to exacerbate the coagulation process.
Collapse
Affiliation(s)
- Ghazal Kakavand
- Department of Biology, Faculty of Basic Science, Ale Taha Institute of Higher Education, Tehran, Iran
| | - Somayeh Arabzadeh
- Department of Biology, Faculty of Basic Science, Ale Taha Institute of Higher Education, Tehran, Iran
| | - Sohameh Mohebbi
- Department of Biology, Faculty of Basic Science, Ale Taha Institute of Higher Education, Tehran, Iran.
| | - Kayvan Saeedfar
- Tracheal Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Atefeh Abedini
- Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Masoud Mardani
- Shahid Beheshti University of Medical Sciences, Infectious Disease Department, Loghman Hakim Hospital, Tehran, Iran
| |
Collapse
|
|
2
|
Stasi C. Post-COVID-19 Pandemic Sequelae in Liver Diseases. Life (Basel) 2025; 15:403. [PMID: 40141748 PMCID: PMC11943493 DOI: 10.3390/life15030403] [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: 02/08/2025] [Revised: 02/27/2025] [Accepted: 03/03/2025] [Indexed: 03/28/2025] Open
Abstract
During the coronavirus disease 2019 (COVID-19) pandemic, several studies highlighted a worse prognosis for patients with alterations in liver function tests, especially those with pre-existing liver diseases. However, further studies are needed to define the long-term impact of the COVID-19 pandemic on liver diseases. Long COVID-19 encompasses a wide range of signs and symptoms, including exacerbations of pre-existing chronic conditions or new onset conditions developed after the COVID-19 acute phase. Therefore, the long-term effects of COVID-19 extensively include hepatic manifestations. The co-expression of angiotensin-converting receptor 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) has been demonstrated also in enterocytes, cholangiocytes, and hepatocytes. Studies on the post-COVID-19 sequelae have shown the presence of steatosis and necroinflammation in the liver, concomitantly with an alteration of inflammation, cytolysis and cholestasis indices. Some studies also demonstrated an increased risk for hepatobiliary pathologies, including secondary biliary cholangitis and worsening of the severity of metabolic-associated fatty liver disease (MASLD). Based on these premises, this review aims to provide an overview of the pathophysiological mechanisms contributing to COVID-19-related liver and hepatobiliary damage; explore its implications for liver inflammation and fibrosis, with a particular focus on MASLD and metabolic dysfunction-associated steatohepatitis (MASH); and analyze the short- and long-term COVID-19 sequelae. A literature search was conducted using the PubMed database for relevant studies published in English.
Collapse
Affiliation(s)
- Cristina Stasi
- Department of Life Science, Health and Health Professions, Link Campus University, 00165 Roma, Italy; or
- Epidemiology Unit, Regional Health Agency of Tuscany, 50141 Florence, Italy
| |
Collapse
|
|
3
|
Sim SY, Cho HD, Lee SB. Amelioration of Alcoholic Hepatic Steatosis in a Rat Model via Consumption of Poly-γ-Glutamic Acid-Enriched Fermented Protaetia brevitarsis Larvae Using Bacillus subtilis. Foods 2025; 14:861. [PMID: 40077563 PMCID: PMC11899319 DOI: 10.3390/foods14050861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 02/23/2025] [Accepted: 02/27/2025] [Indexed: 03/14/2025] Open
Abstract
Alcoholic hepatic steatosis (AHS) is a common early-stage symptom of liver disease caused by alcohol consumption. Accordingly, several aspects of AHS have been studied as potential preventive and therapeutic targets. In this study, a novel strategy was employed to inhibit fatty liver accumulation and counteract AHS through the consumption of microorganism-fermented Protaetia brevitarsis larvae (FPBs). By using an AHS rat model, we assessed the efficacy of FPB by examining the lipid profile of liver/serum and liver function tests to evaluate lipid metabolism modulation. After FPB administration, the lipid profile-including high-density lipoprotein, total cholesterol, and total triglycerides-and histopathological characteristics exhibited improvement in the animal model. Interestingly, AHS amelioration via FPBs administration was potentially associated with poly-γ-glutamic acid (PγG), which is produced by Bacillus species during fermentation. These findings support the formulation of novel natural remedies for AHS through non-clinical animal studies, suggesting that PγG-enriched FPBs are a potentially valuable ingredient for functional foods, providing an ameliorative effect on AHS.
Collapse
Affiliation(s)
- So-Yeon Sim
- School of Food Science and Biotechnology, Kyungpook National University, 80 Daehak-ro, Daegu 41566, Republic of Korea;
| | - Hyun-Dong Cho
- Department of Food and Nutrition, Sunchon National University, Sunchon 57922, Republic of Korea;
| | - Sae-Byuk Lee
- School of Food Science and Biotechnology, Kyungpook National University, 80 Daehak-ro, Daegu 41566, Republic of Korea;
- Institute of Fermentation Biotechnology, Kyungpook National University, 80 Daehak-ro, Daegu 41566, Republic of Korea
| |
Collapse
|
|
4
|
Chen S, Zhang Y, Ashuo A, Song S, Yuan L, Wang W, Wang C, Du Z, Wu Y, Tan D, Huang C, Chen J, Li Y, Bai J, Guo H, Huang Z, Guan Y, Xia N, Yuan Z, Zhang J, Yuan Q, Fang Z. Combination of spatial transcriptomics analysis and retrospective study reveals liver infection of SARS-COV-2 is associated with clinical outcomes of COVID-19. EBioMedicine 2025; 111:105517. [PMID: 39709771 PMCID: PMC11732063 DOI: 10.1016/j.ebiom.2024.105517] [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: 07/11/2024] [Revised: 12/06/2024] [Accepted: 12/09/2024] [Indexed: 12/24/2024] Open
Abstract
BACKGROUND Liver involvement is a common complication of coronavirus disease 2019 (COVID-19), especially in hospitalized patients. However, the underlying mechanisms involved are not fully understood. METHODS Immunohistochemistry (IHC) staining of SARS-CoV-2 spike (S) and nucleocapsid (N) proteins was conducted on liver tissues from six patients with COVID-19. The 10x Genomics Visium CytAssist Spatial Gene Assay was designed to analyze liver transcriptomics. TCR CDR3 sequences were analyzed in DNA from liver tissues. Liver function indicators were retrospectively studied in 650 hospitalized patients with COVID-19. FINDINGS SARS-CoV-2 proteins were initially detected in the livers of naturally infected golden (Syrian) hamsters, prompting us to investigate the situation in clinical cases. Thus, we collected liver tissues from patients with abnormal liver biochemical values. Viral S and N proteins were detected in the livers of severe and deceased patients but not in those of moderate patients. We further demonstrated that hepatocytes and erythroid cells in hepatic sinusoids are major cells targeted by SARS-CoV-2. Immune cells, especially T cells, were enriched in surviving severe patients, characterized by enhanced CDR3α clonality and novel CDR3β recombination of the T-cell receptor. In contrast, hepatocyte apoptosis was triggered, and the transcription of albumin (ALB) was obviously impaired in the deceased patients. We then performed a retrospective study including patients with COVID-19. Serum aspartate aminotransferase (AST) and ALB levels at baseline significantly differed in the deceased cohort. However, AST regression did not decrease the risk of death. ALB recovery indicated clinical improvement, and declining or low serum ALB concentrations were associated with death. INTERPRETATION This study provides clinical evidence for liver infection with SARS-CoV-2, insight into the impact of SARS-CoV-2 on the liver, and a potential way to evaluate the risk of death via assessing serum ALB concentration fluctuations in patients with COVID-19. FUNDING National Key R&D Program of China (2021YFC2300602), National Natural Science Foundation of China (92369110), National Natural Science Foundation of China (U23A20474), Shanghai Municipal Science and Technology Major Project (ZD2021CY001), Shanghai Jinshan District Medical and Health Technology Innovation Fund Project (2023-WS-31).
Collapse
Affiliation(s)
- Shiqi Chen
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Yi Zhang
- Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, Shanghai, China
| | - Asha Ashuo
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
| | - Shu Song
- Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, Shanghai, China
| | - Lunzhi Yuan
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China
| | - Weixia Wang
- Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, China
| | - Cong Wang
- Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, Shanghai, China
| | - Zunguo Du
- Department of Pathology, Huashan Hospital, Fudan University, Shanghai, China
| | - Yangtao Wu
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China
| | - Dan Tan
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
| | - Chenlu Huang
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China
| | - Jingna Chen
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yaming Li
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jinjin Bai
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China
| | - Huilin Guo
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China
| | - Zehong Huang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China
| | - Yi Guan
- State Key Laboratory of Emerging Infectious Diseases, University of Hong Kong, Hong Kong, China; Joint Institute of Virology (Shantou University and University of Hong Kong), Guangdong-Hongkong Joint Laboratory of Emerging Infectious Diseases, Shantou University, Shantou, China
| | - Ningshao Xia
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China.
| | - Zhenghong Yuan
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
| | - Jiming Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
| | - Quan Yuan
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China.
| | - Zhong Fang
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China.
| |
Collapse
|
|
5
|
Mekuanint A, Ambachew S, Worede A, Asrie F, Sinishaw MA, Gelaw Y, Dagnew M, Gelaw A, Negash M, Kassa E, Bizuneh S, Wudineh D, Dimah B, Abebe W, Chane E, Fetene G. Assessment of abnormal liver function tests and associated factors among COVID-19-infected patients in Addis Ababa, Ethiopia, 2022: a facility-based comparative cross-sectional study. BMJ Open 2024; 14:e076647. [PMID: 39260868 PMCID: PMC11409313 DOI: 10.1136/bmjopen-2023-076647] [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: 06/16/2023] [Accepted: 07/19/2024] [Indexed: 09/13/2024] Open
Abstract
OBJECTIVE Liver function test (LFT) abnormalities are higher in patients with severe COVID-19. Most of the studies on this theme were conducted in foreign nations, and the association with LFT abnormalities was not sufficiently addressed in the study areas. Therefore, the current study aimed to investigate the effects of COVID-19 infection on liver function of patients. SETTING A facility-based comparative cross-sectional study was carried out from 10 April to 15 June 2022, among COVID-19 infected individuals admitted in Eka Kotebe General Hospital and Saint Petrous Specialized Hospitals, Addis Ababa, 2022. PARTICIPANTS A total of 284 confirmed COVID-19-positive and COVID-19-negative controls matched by gender and age were included in the present study. RESULTS Among SARS-COV-2 positive groups, 63 (44.4%) had one or more LFT abnormalities. The most common elevated level of the LFTs among patients with COVID-19 were gamma-glutamyl transferase (GGT) 50 (35.2%), while the most common lowered level was albumin 58 (40.8%). The mean values of aspartate aminotransferase (AST) (35.4±26.9 vs 22.9±12.6, p<0.001) were significantly different between patients with COVID-19 and the COVID-19-free groups. Being COVID-19-positive was significantly associated with an elevated level of AST (AOR=3.0, 95% CI 1.2 to 7.4) and GGT (AOR=4.55, 95% CI 2.02 to 10.3). Being male was significantly associated with an elevated level of total bilirubin (BILT, AOR=2.41, 95% CI 1.2 to 4.9) and direct bilirubin (BILD, AOR=3.7, 95% CI 1.72 to 8.2), and also severe stage of COVID-19 was associated with hypoalbuminaemia (AOR=3.3, 95% CI 1.4 to 7.9). SARS-COV-2 infection was independently associated with LFT abnormality. CONCLUSION Patients with COVID-19 had decreased albumin levels, and elevated AST, GGT, BILT and BILD levels.
Collapse
Affiliation(s)
- Amare Mekuanint
- Department of Clinical Chemistry, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Sintayehu Ambachew
- Department of Clinical Chemistry, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
- Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
| | - Abebaw Worede
- Department of Clinical Chemistry, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Fikir Asrie
- Department of Hematology and Immunohematology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Mulusew Alemneh Sinishaw
- Department of Clinical Chemistry, College of Medicine and Health Science, Bahir Dar University, Bahir Dar, Ethiopia
| | - Yemataw Gelaw
- Department of Hematology and Immunohematology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Mulat Dagnew
- Department of Medical Microbiology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Aschalew Gelaw
- Department of Medical Microbiology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Markos Negash
- Department of Immunology and Molecular Biology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Eyuel Kassa
- University of Gondar Comprehensive Specialized Hospital Laboratory, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Segenet Bizuneh
- Department of Internal Medicine, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Dessalew Wudineh
- Department of Medical Laboratory Sciences, Institute of Health Sciences, Mizan Tepi University, Mizan Tepi, Ethiopia
| | - Belayneh Dimah
- Department of Microbiology, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia
| | - Wagaw Abebe
- Department of Medical Laboratory Sciences, College of Health Sciences, Woldia University, Woldia, Ethiopia
| | - Elias Chane
- Department of Clinical Chemistry, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Getnet Fetene
- Department of Clinical Chemistry, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| |
Collapse
|
|
6
|
Antar SA, Ashour NA, Hamouda AO, Noreddin AM, Al-Karmalawy AA. Recent advances in COVID-19-induced liver injury: causes, diagnosis, and management. Inflammopharmacology 2024:10.1007/s10787-024-01535-7. [PMID: 39126569 DOI: 10.1007/s10787-024-01535-7] [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: 10/14/2023] [Accepted: 03/29/2024] [Indexed: 08/12/2024]
Abstract
Since the start of the pandemic, considerable advancements have been made in our understanding of the effects of SARS-CoV-2 infection and the associated COVID-19 on the hepatic system. There is a broad range of clinical symptoms for COVID-19. It affects multiple systems and has a dominant lung illness depending on complications. The progression of COVID-19 in people with pre-existing chronic liver disease (CLD) has also been studied in large multinational groups. Notably, SARS-CoV-2 infection is associated with a higher risk of hepatic decompensation and death in patients with cirrhosis. In this review, the source, composition, mechanisms, transmission characteristics, clinical characteristics, therapy, and prevention of SARS-CoV-2 were clarified and discussed, as well as the evolution and variations of the virus. This review briefly discusses the causes and effects of SARS-CoV-2 infection in patients with CLD. As part of COVID-19, In addition, we assess the potential of liver biochemistry as a diagnostic tool examine the data on direct viral infection of liver cells, and investigate potential pathways driving SARS-CoV-2-related liver damage. Finally, we explore how the pandemic has had a significant impact on patient behaviors and hepatology services, which may increase the prevalence and severity of liver disease in the future. The topics encompassed in this review encompass the intricate relationships between SARS-CoV-2, liver health, and broader health management strategies, providing valuable insights for both current clinical practice and future research directions.
Collapse
Affiliation(s)
- Samar A Antar
- Center for Vascular and Heart Research, Fralin Biomedical Research Institute, Virginia Tech, Roanoke, VA, 24016, USA
- Department of Pharmacology, Faculty of Pharmacy, Horus University-Egypt, New Damietta, 34518, Egypt
| | - Nada A Ashour
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt
| | - Amir O Hamouda
- Department of Biochemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta, 34518, Egypt
| | - Ayman M Noreddin
- Department of Clinical Pharmacy, Faculty of Pharmacy, Ahram Canadian University, 6Th of October City, Giza, 12566, Egypt
- Department of Internal Medicine, School of Medicine, University of California -Irvine, Irvine, USA
| | - Ahmed A Al-Karmalawy
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta, New Damietta, 34518, Egypt.
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, 6Th of October City, Giza, 12566, Egypt.
| |
Collapse
|
|
7
|
Agarwal R, Bhugra A, Gautam P, Suroliya V, Chhabra R, Pandey A, Garg P, Rao P, Babu R, Kumar G, Bihari C, Bhattacharyya D, Shasthry SM, Sarin SK, Gupta E. Clinical and Genomic Perspective of SARS CoV-2 Infection in Liver Disease Patients: A Single-Centre Retrospective Study. Curr Microbiol 2024; 81:301. [PMID: 39115704 DOI: 10.1007/s00284-024-03786-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Accepted: 06/22/2024] [Indexed: 08/15/2024]
Abstract
The limited literature on the clinical course of COVID-19 among patients with underlying liver disease (LD) is available from India. The present study aimed to evaluate the clinical and mutational profile of SARS-CoV-2 among LD cases. This was a retrospective study including admitted LD cases in whom SARS-CoV-2 RT-PCR testing was performed. Complete demographic and clinical details were retrieved from Hospital Information System. Detailed mutational analysis was performed by comparing LD COVID-19 positive study group, i.e. LD-CoV(+) with COVID-19 positive outpatients without any underlying LD as control, i.e. NLD-CoV(+). Out of 232 enrolled LD cases, 137 (59.1%) were LD-CoV(+). LD cases with existing co-morbidities were affected more (P = 0.002) and had 2.29 times (OR 2.29, CI 95%, 1.25-4.29) higher odds of succumbing to COVID-19 (P = 0.006). On multivariate regression analysis, ascites (P = 0.05), severe COVID-19 pneumonia (P = 0.046), and an increased levels of bilirubin (P = 0.005) and alkaline phosphatase (P = 0.003) were found to be associated with adverse outcome in LD-CoV(+).On mutational analysis, we found certain differences between LD- and NLD-CoV(+) infected with Delta [LD- and NLD-CoV (+ /D)] and Omicron [LD- and NLD-CoV(+/O)]. More mutations were shared between LD- and NLD-CoV(+/O) compared to LD- and NLD-CoV(+/D). There were differences in prevalence of indel mutations specific to LD-CoV ( +) for both Delta and Omicron. Moreover, we also reported an interesting genic bias between LD- and NLD-CoV( +) in harbouring deleterious/tolerated mutations. To conclude, LD cases with comorbidities were affected more and had higher odds of mortality due to COVID-19. The definite difference between LD- and NLD-CoV(+) groups with respect to frequency of harboured mutations and an inherent genic bias between them is of noteworthy importance.
Collapse
Affiliation(s)
- Reshu Agarwal
- Department of Clinical Virology, Institute of Liver and Biliary Sciences, D-1 Vasant Kunj, New Delhi, 110070, India
| | - Arjun Bhugra
- Department of Clinical Virology, Institute of Liver and Biliary Sciences, D-1 Vasant Kunj, New Delhi, 110070, India
| | - Pramod Gautam
- Genome Sequencing Laboratory, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Varun Suroliya
- Genome Sequencing Laboratory, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ruchita Chhabra
- Department of Clinical Virology, Institute of Liver and Biliary Sciences, D-1 Vasant Kunj, New Delhi, 110070, India
| | - Amit Pandey
- Department of Clinical Virology, Institute of Liver and Biliary Sciences, D-1 Vasant Kunj, New Delhi, 110070, India
| | - Prince Garg
- Genome Sequencing Laboratory, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Pooja Rao
- Genome Sequencing Laboratory, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rosmy Babu
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Guresh Kumar
- Department of Biostatistics, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Chhagan Bihari
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - S M Shasthry
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ekta Gupta
- Department of Clinical Virology, Institute of Liver and Biliary Sciences, D-1 Vasant Kunj, New Delhi, 110070, India.
| |
Collapse
|
|
8
|
Lau JYS, O'Hara S, Lombardo P, Goodyear M. Assessment of the liver with two-dimensional shear wave elastography following COVID-19 infection: A pilot study. Australas J Ultrasound Med 2024; 27:167-173. [PMID: 39328255 PMCID: PMC11423436 DOI: 10.1002/ajum.12390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/28/2024] Open
Abstract
Introduction/Purpose The coronavirus disease (COVID-19) is a widely spread viral infectious disease, which can impact multiple organs, including the liver. Elevated liver enzymes have been reported in COVID-19 patients; however, potential changes in liver stiffness following the viral infection remain uncertain. The main aim of this pilot study was to determine if there is a significant difference in liver stiffness between individuals who have never been infected with COVID-19 and those who had been infected with COVID-19 <6 months, experiencing only mild symptoms. The secondary aim was to compare the liver stiffness between participants infected with COVID-19 depending on the elapsed time since infection. Methods Two-dimensional shear wave elastography (2D-SWE) was performed prospectively on 68 participants. Thirty-four participants had been infected with COVID-19 (all for <6 months) (COVID-19 group), and another 34 had never been infected with COVID-19 (control group). The mean 2D-SWE measurements of both the COVID-19 group and the control group were compared using an independent t-test. The mean 2D-SWE measurements of the COVID-19 subgroups A (<2 months), B (2 to <4 months) and C (4 to <6 months) were compared using a one-way ANOVA test (P < 0.05). Results The (mean ± standard deviation) liver stiffness (kPa) of the COVID-19 group (5.26 ± 1.63 kPa) was significantly higher than the control group (4.30 ± 0.96 kPa) (P = 0.005). There was no significant difference in liver stiffness among subgroups A (5.20 ± 1.79 kPa), B (4.70 ± 1.53 kPa) and C (5.96 ± 1.48 kPa) (P = 0.143) respectively. Discussion The mean liver stiffness of 4.30 ± 0.96k Pa in the control group showed a high probability of being normal as per guidelines. Conversely, the mean liver stiffness of 5.26 ± 1.63 kPa in the COVID-19 group exhibited a statistically significant increase compared to the control group. However, compensated advanced chronic liver disease was ruled out without other known clinical signs, as per guidelines. Conclusion A statistically significant increase in liver stiffness value was observed in the post-COVID-19 infection group compared to the group who had never been infected. This highlights the potential for short-term impact on liver stiffness associated with COVID-19 infection. However, it is unclear if these changes in liver stiffness are associated with liver injury. Further study is warranted to investigate the effects of COVID-19 infection and its long-term impact on the liver.
Collapse
Affiliation(s)
- Joyce Yea See Lau
- SKG RadiologyLevel 3, 1 Hood StreetSubiaco6008Western AustraliaAustralia
- Department of Medical Imaging and Radiation SciencesMonash UniversityWellington RdClayton3800VictoriaAustralia
| | - Sandra O'Hara
- SKG RadiologyLevel 3, 1 Hood StreetSubiaco6008Western AustraliaAustralia
| | - Paul Lombardo
- Department of Medical Imaging and Radiation SciencesMonash UniversityWellington RdClayton3800VictoriaAustralia
| | - Melinda Goodyear
- School of Rural HealthMonash UniversityWellington RdClayton3800VictoriaAustralia
| |
Collapse
|
|
9
|
Huang X, Liu X, Li Z. Bile acids and coronavirus disease 2019. Acta Pharm Sin B 2024; 14:1939-1950. [PMID: 38799626 PMCID: PMC11119507 DOI: 10.1016/j.apsb.2024.02.011] [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: 08/14/2023] [Revised: 12/08/2023] [Accepted: 01/28/2024] [Indexed: 05/29/2024] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been significantly alleviated. However, long-term health effects and prevention strategy remain unresolved. Thus, it is essential to explore the pathophysiological mechanisms and intervention for SARS-CoV-2 infection. Emerging research indicates a link between COVID-19 and bile acids, traditionally known for facilitating dietary fat absorption. The bile acid ursodeoxycholic acid potentially protects against SARS-CoV-2 infection by inhibiting the farnesoid X receptor, a bile acid nuclear receptor. The activation of G-protein-coupled bile acid receptor, another membrane receptor for bile acids, has also been found to regulate the expression of angiotensin-converting enzyme 2, the receptor through which the virus enters human cells. Here, we review the latest basic and clinical evidence linking bile acids to SARS-CoV-2, and reveal their complicated pathophysiological mechanisms.
Collapse
Affiliation(s)
- Xiaoru Huang
- Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China
- Department of Pharmaceutical Management and Clinical Pharmacy, College of Pharmacy, Peking University, Beijing 100191, China
| | - Xuening Liu
- Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China
- Department of Pharmaceutical Management and Clinical Pharmacy, College of Pharmacy, Peking University, Beijing 100191, China
| | - Zijian Li
- Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China
- Department of Pharmaceutical Management and Clinical Pharmacy, College of Pharmacy, Peking University, Beijing 100191, China
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing Key Laboratory of Cardiovascular Receptors Research, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China
| |
Collapse
|
|
10
|
Shoraka S, Mohebbi SR, Hosseini SM, Ghaemi A, Zali MR. SARS-CoV-2 and chronic hepatitis B: Focusing on the possible consequences of co-infection. JOURNAL OF CLINICAL VIROLOGY PLUS 2023; 3:100167. [DOI: 10.1016/j.jcvp.2023.100167] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
|
|
11
|
Lerner A, Benzvi C, Vojdani A. SARS-CoV-2 Gut-Targeted Epitopes: Sequence Similarity and Cross-Reactivity Join Together for Molecular Mimicry. Biomedicines 2023; 11:1937. [PMID: 37509576 PMCID: PMC10376948 DOI: 10.3390/biomedicines11071937] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 07/02/2023] [Accepted: 07/06/2023] [Indexed: 07/30/2023] Open
Abstract
The gastrointestinal tract can be heavily infected by SARS-CoV-2. Being an auto-immunogenic virus, SARS-CoV-2 represents an environmental factor that might play a role in gut-associated autoimmune diseases. However, molecular mimicry between the virus and the intestinal epitopes is under-investigated. The present study aims to elucidate sequence similarity between viral antigens and human enteric sequences, based on known cross-reactivity. SARS-CoV-2 epitopes that cross-react with human gut antigens were explored, and sequence alignment was performed against self-antigens implicated in enteric autoimmune conditions. Experimental SARS-CoV-2 epitopes were aggregated from the Immune Epitope Database (IEDB), while enteric antigens were obtained from the UniProt Knowledgebase. A Pairwise Local Alignment tool, EMBOSS Matcher, was employed for the similarity search. Sequence similarity and targeted cross-reactivity were depicted between 10 pairs of immunoreactive epitopes. Similar pairs were found in four viral proteins and seven enteric antigens related to ulcerative colitis, primary biliary cholangitis, celiac disease, and autoimmune hepatitis. Antibodies made against the viral proteins that were cross-reactive with human gut antigens are involved in several essential cellular functions. The relationship and contribution of those intestinal cross-reactive epitopes to SARS-CoV-2 or its potential contribution to gut auto-immuno-genesis are discussed.
Collapse
Affiliation(s)
- Aaron Lerner
- Chaim Sheba Medical Center, The Zabludowicz Research Center for Autoimmune Diseases, Ramat Gan 52621, Israel;
- Research Department, Ariel University, Ariel 40700, Israel
| | - Carina Benzvi
- Chaim Sheba Medical Center, The Zabludowicz Research Center for Autoimmune Diseases, Ramat Gan 52621, Israel;
| | | |
Collapse
|
|
12
|
Akbari H, Taghizadeh-Hesary F. COVID-19 induced liver injury from a new perspective: Mitochondria. Mitochondrion 2023; 70:103-110. [PMID: 37054906 PMCID: PMC10088285 DOI: 10.1016/j.mito.2023.04.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 01/27/2023] [Accepted: 04/07/2023] [Indexed: 04/15/2023]
Abstract
Liver damage is a common sequela of COVID-19 (coronavirus disease 2019), worsening the clinical outcomes. However, the underlying mechanism of COVID-induced liver injury (CiLI) is still not determined. Given the crucial role of mitochondria in hepatocyte metabolism and the emerging evidence denoting SARS-CoV-2 can damage human cell mitochondria, in this mini-review, we hypothesized that CiLI happens following hepatocytes' mitochondrial dysfunction. To this end, we evaluated the histologic, pathophysiologic, transcriptomic, and clinical features of CiLI from the mitochondria' eye view. Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the causative agent of COVID-19, can damage hepatocytes through direct cytopathic effects or indirectly after the profound inflammatory response. Upon entering the hepatocytes, the RNA and RNA transcripts of SARS-CoV-2 engages the mitochondria. This interaction can disrupt the mitochondrial electron transport chain. In other words, SARS-CoV-2 hijacks the hepatocytes' mitochondria to support its replication. In addition, this process can lead to an improper immune response against SARS-CoV-2. Besides, this review outlines how mitochondrial dysfunction can serve as a prelude to the COVID-associated cytokine storm. Thereafter, we indicate how the nexus between COVID-19 and mitochondria can fill the gap linking CiLI and its risk factors, including old age, male sex, and comorbidities. In conclusion, this concept stresses the importance of mitochondrial metabolism in hepatocyte damage in the context of COVID-19. It notes that boosting mitochondria biogenesis can possibly serve as a prophylactic and therapeutic approach for CiLI. Further studies can reveal this notion.
Collapse
Affiliation(s)
- Hassan Akbari
- Department of Pathology, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Traditional Medicine School, Tehran University of Medical Sciences, Tehran, Iran
| | - Farzad Taghizadeh-Hesary
- ENT and Head and Neck Research Center and Department, The Five Senses Health Institute, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
13
|
Ayyashi M, Darbashi H, Hakami A, Sharahili F. Evaluation of Remdesivir Utilization Pattern in Critically Ill Patients With COVID-19 in Jazan Province. Cureus 2023; 15:e36247. [PMID: 37069861 PMCID: PMC10105617 DOI: 10.7759/cureus.36247] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/16/2023] [Indexed: 03/17/2023] Open
Abstract
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has spread around the world, spurring the biomedical community to find and create antiviral therapies. The agent remdesivir, which has undergone a protracted and tortuous developmental path, is one potential therapeutic strategy now being assessed in several clinical trials. A broad-spectrum antiviral drug called remdesivir has already shown antiviral effects against filoviruses. Remdesivir was suggested as an exploratory medicine early in the pandemic because in vitro tests showed it to have antiviral effectiveness against SARS-CoV-2. Methods We conducted a retrospective cohort study that examined patient data captured through an electronic medical system at the Abu Arish General Hospital between 2021 and 2022. Data analysis was performed with SPSS version 25.0 (Armonk, NY: IBM Corp.). Results A total of 88 patients were included in this study. With the usage of remdesivir, our risk model is able to forecast adverse events and the case fatality rate. In contrast to D-dimer and c-reactive proteins, we showed that alanine transaminase (ALT), aspartate aminotransferase (AST), serum creatinine, and hemoglobin are relevant variables. Conclusion Our risk model can predict the adverse reactions and case fatality rate with the use of remdesivir. We demonstrated ALT, AST, serum creatinine, and hemoglobin as important variables rather than D-dimer and c-reactive proteins.
Collapse
|
|
14
|
Papagiouvanni I, Kotoulas SC, Pataka A, Spyratos DG, Porpodis K, Boutou AK, Papagiouvannis G, Grigoriou I, Vettas C, Goulis I. COVID-19 and liver injury: An ongoing challenge. World J Gastroenterol 2023; 29:257-271. [PMID: 36687117 PMCID: PMC9846934 DOI: 10.3748/wjg.v29.i2.257] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 11/29/2022] [Accepted: 12/21/2022] [Indexed: 01/06/2023] Open
Abstract
The new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in December 2019, in Wuhan, China. The virus was rapidly spread worldwide, causing coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 is presented, usually, with typical respiratory symptoms (i.e., dyspnea, cough) and fever, extrapulmonary manifestations are also encountered. Liver injury is a common feature in patients with COVID-19 and ranges from mild and temporary elevation of liver enzymes to severe liver injury and, even, acute liver failure. The pathogenesis of liver damage is not clearly defined; multiple mechanisms contribute to liver disorder, including direct cytopathic viral effect, cytokine storm and immune-mediated hepatitis, hypoxic injury, and drug-induced liver toxicity. Patients with underlying chronic liver disease (i.e., cirrhosis, non-alcoholic fatty liver disease, alcohol-related liver disease, hepatocellular carcinoma, etc.) may have greater risk to develop both severe COVID-19 and further liver deterioration, and, as a consequence, certain issues should be considered during disease management. The aim of this review is to present the prevalence, clinical manifestation and pathophysiological mechanisms of liver injury in patients with SARS-CoV-2 infection. Moreover, we overview the association between chronic liver disease and SARS-CoV-2 infection and we briefly discuss the management of liver injury during COVID-19.
Collapse
Affiliation(s)
- Ioanna Papagiouvanni
- Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Thessaloniki, Greece
| | | | - Athanasia Pataka
- Department of Respiratory Medicine, G Papanikolaou Hospital, Resp Failure Unit, Aristotle University of Thessaloniki, Thessaloniki 57001, Greece
| | - Dionisios G Spyratos
- Pulmonary Department, Aristotle University of Thessaloniki, Thessaloniki 57001, Greece
| | - Konstantinos Porpodis
- Pulmonary Department, Aristotle University of Thessaloniki, Thessaloniki 57001, Greece
| | - Afroditi K Boutou
- Pulmonary Department, G Papanikolaou Hospital, Resp Failure Unit, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - Georgios Papagiouvannis
- Department of Pharmacy, School of Health Sciences, Frederick University, Nicosia 1036, Cyprus
| | - Ioanna Grigoriou
- Respiratory Failure Clinic, Papanikolaou General Hospital, Thessloniki 57001, Greece
| | - Christos Vettas
- Fourth Department of Internal Medicine, Hippokration General Hospital, Thessaloniki 54642, Greece
| | - Ioannis Goulis
- Fourth Department of Internal Medicine, Hippokration General Hospital, Thessaloniki 54642, Greece
| |
Collapse
|
|
15
|
Zhao SW, Li YM, Li YL, Su C. Liver injury in COVID-19: Clinical features, potential mechanisms, risk factors and clinical treatments. World J Gastroenterol 2023; 29:241-256. [PMID: 36687127 PMCID: PMC9846943 DOI: 10.3748/wjg.v29.i2.241] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 11/11/2022] [Accepted: 12/08/2022] [Indexed: 01/06/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has been a serious threat to global health for nearly 3 years. In addition to pulmonary complications, liver injury is not uncommon in patients with novel COVID-19. Although the prevalence of liver injury varies widely among COVID-19 patients, its incidence is significantly increased in severe cases. Hence, there is an urgent need to understand liver injury caused by COVID-19. Clinical features of liver injury include detectable liver function abnormalities and liver imaging changes. Liver function tests, computed tomography scans, and ultrasound can help evaluate liver injury. Risk factors for liver injury in patients with COVID-19 include male sex, preexisting liver disease including liver transplantation and chronic liver disease, diabetes, obesity, and hypertension. To date, the mechanism of COVID-19-related liver injury is not fully understood. Its pathophysiological basis can generally be explained by systemic inflammatory response, hypoxic damage, ischemia-reperfusion injury, and drug side effects. In this review, we systematically summarize the existing literature on liver injury caused by COVID-19, including clinical features, underlying mechanisms, and potential risk factors. Finally, we discuss clinical management and provide recommendations for the care of patients with liver injury.
Collapse
Affiliation(s)
- Shu-Wu Zhao
- Department of Anesthesiology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, Hunan Province, China
| | - Yi-Ming Li
- School of Basic Medical Science, Naval Medical University/Second Military University, Shanghai 200433, China
| | - Yi-Lin Li
- Department of Pathology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, Hunan Province, China
| | - Chen Su
- Department of Anesthesiology and Pain, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, Hunan Province, China
| |
Collapse
|
|
16
|
Saha L, Vij S, Rawat K. Liver injury induced by COVID 19 treatment - what do we know? World J Gastroenterol 2022; 28:6314-6327. [PMID: 36533104 PMCID: PMC9753058 DOI: 10.3748/wjg.v28.i45.6314] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 10/07/2022] [Accepted: 11/17/2022] [Indexed: 12/02/2022] Open
Abstract
The severity of coronavirus disease 2019 (COVID-19) may be correlated with the risk of liver injury development. An increasing number of studies indicate that degrees of hepatotoxicity have been associated with using some medications in the management of COVID-19 patients. However, limited studies have systematically investigated the evidence of drug-induced liver injury (DILI) in COVID-19 patients. An increasing number of studies indicate that degrees of hepatotoxicity have been associated with using some of these medications in the management of COVID-19 patients. Significantly, it was relieved after the cessation of these agents. However, to our knowledge, no studies have systematically investigated the evidence of DILI in COVID-19 patients. In this review, we discussed the association between hepatotoxicity in COVID-19 patients and the drugs used in these patients and possible mechanisms of hepatotoxicity. The currently available evidence on the association of different therapeutic agents with hepatotoxicity in COVID-19 patient was systematically reviewed.
Collapse
Affiliation(s)
- Lekha Saha
- Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Soumya Vij
- Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Kajal Rawat
- Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| |
Collapse
|
|
17
|
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].
Collapse
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
| |
Collapse
|
|
18
|
Schwarz S, Lang C, Harlander M, Štupnik T, Slambrouck JV, Ceulemans LJ, Ius F, Gottlieb J, Kuhnert S, Hecker M, Aigner C, Kneidinger N, Verschuuren EAM, Smits JM, Tschernko E, Schaden E, Faybik P, Markstaller K, Trauner M, Jaksch P, Hoetzenecker K. Gamma-glutamyltransferase is a strong predictor of secondary sclerosing cholangitis after lung transplantation for COVID-19 ARDS. J Heart Lung Transplant 2022; 41:1501-1510. [PMID: 35907758 PMCID: PMC9249665 DOI: 10.1016/j.healun.2022.06.020] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 06/20/2022] [Accepted: 06/24/2022] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND Lung transplantation (LTx) can be considered for selected patients suffering from COVID-19 acute respiratory distress syndrome (ARDS). Secondary sclerosing cholangitis in critically ill (SSC-CIP) patients has been described as a late complication in COVID-19 ARDS survivors, however, rates of SSC-CIP after LTx and factors predicting this detrimental sequela are unknown. METHODS This retrospective analysis included all LTx performed for post-COVID ARDS at 8 European LTx centers between May 2020 and January 2022. Clinical risk factors for SSC-CIP were analyzed over time. Prediction of SSC-CIP was assessed by ROC-analysis. RESULTS A total of 40 patients were included in the analysis. Fifteen patients (37.5%) developed SSC-CIP. GGT at the time of listing was significantly higher in patients who developed SSC-CIP (median 661 (IQR 324-871) vs 186 (109-346); p = 0.001). Moreover, higher peak values for GGT (585 vs 128.4; p < 0.001) and ALP (325 vs 160.2; p = 0.015) were found in the 'SSC' group during the waiting period. Both, GGT at the time of listing and peak GGT during the waiting time, could predict SSC-CIP with an AUC of 0.797 (95% CI: 0.647-0.947) and 0.851 (95% CI: 0.707-0.995). Survival of 'SSC' patients was severely impaired compared to 'no SSC' patients (1-year: 46.7% vs 90.2%, log-rank p = 0.004). CONCLUSIONS SSC-CIP is a severe late complication after LTx for COVID-19 ARDS leading to significant morbidity and mortality. GGT appears to be a sensitive parameter able to predict SSC-CIP even at the time of listing.
Collapse
Affiliation(s)
- Stefan Schwarz
- Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Christian Lang
- Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Matevz Harlander
- Department of Pulmonary Diseases, University Medical Center, Ljubljana, Slovenia
| | - Tomaz Štupnik
- Department of Thoracic Surgery, University Medical Center, Ljubljana, Slovenia
| | - Jan Van Slambrouck
- Department of Thoracic Surgery, Lab of BREATHE, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - Laurens J. Ceulemans
- Department of Thoracic Surgery, Lab of BREATHE, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - Fabio Ius
- Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Hannover, Germany
| | - Jens Gottlieb
- Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany
| | - Stefan Kuhnert
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine II, University Hospital Giessen, Justus Liebig University of Giessen, Giessen, Germany
| | - Matthias Hecker
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine II, University Hospital Giessen, Justus Liebig University of Giessen, Giessen, Germany
| | - Clemens Aigner
- Department of Thoracic Surgery, West German Cancer Center, University Medicine Essen - Ruhrlandklinik, Essen, Germany
| | - Nikolaus Kneidinger
- Department of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center (CPC), Member of German Center for Lung Research (DZL), Munich, Germany
| | - Erik AM. Verschuuren
- Department of Respiratory Diseases, Tuberculosis and Lung Transplantation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | | | - Edda Tschernko
- Division of Cardiac, Thoracic and Vascular Anesthesia and Intensive Care, Medical University of Vienna, Vienna, Austria
| | - Eva Schaden
- Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria
| | - Peter Faybik
- Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria
| | - Klaus Markstaller
- Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Peter Jaksch
- Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Konrad Hoetzenecker
- Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria,Reprint requests: Konrad Hoetzenecker, MD PhD, Division of Thoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna. Telephone: +43-1-404-005-6440. Fax: +43-1-404-005-1000
| |
Collapse
|
|
19
|
Huang J, Zhang Z, Hao C, Qiu Y, Tan R, Liu J, Wang X, Yang W, Qu H. Identifying Drug-Induced Liver Injury Associated With Inflammation-Drug and Drug-Drug Interactions in Pharmacologic Treatments for COVID-19 by Bioinformatics and System Biology Analyses: The Role of Pregnane X Receptor. Front Pharmacol 2022; 13:804189. [PMID: 35979235 PMCID: PMC9377275 DOI: 10.3389/fphar.2022.804189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 06/24/2022] [Indexed: 11/13/2022] Open
Abstract
Of the patients infected with coronavirus disease 2019 (COVID-19), approximately 14–53% developed liver injury resulting in poor outcomes. Drug-induced liver injury (DILI) is the primary cause of liver injury in COVID-19 patients. In this study, we elucidated liver injury mechanism induced by drugs of pharmacologic treatments against SARS-CoV-2 (DPTS) using bioinformatics and systems biology. Totally, 1209 genes directly related to 216 DPTS (DPTSGs) were genes encoding pharmacokinetics and therapeutic targets of DPTS and enriched in the pathways related to drug metabolism of CYP450s, pregnane X receptor (PXR), and COVID-19 adverse outcome. A network, constructed by 110 candidate targets which were the shared part of DPTSGs and 445 DILI targets, identified 49 key targets and four Molecular Complex Detection clusters. Enrichment results revealed that the 4 clusters were related to inflammatory responses, CYP450s regulated by PXR, NRF2-regualted oxidative stress, and HLA-related adaptive immunity respectively. In cluster 1, IL6, IL1B, TNF, and CCL2 of the top ten key targets were enriched in COVID-19 adverse outcomes pathway, indicating the exacerbation of COVID-19 inflammation on DILI. PXR-CYP3A4 expression of cluster 2 caused DILI through inflammation-drug interaction and drug-drug interactions among pharmaco-immunomodulatory agents, including tocilizumab, glucocorticoids (dexamethasone, methylprednisolone, and hydrocortisone), and ritonavir. NRF2 of cluster 3 and HLA targets of cluster four promoted DILI, being related to ritonavir/glucocorticoids and clavulanate/vancomycin. This study showed the pivotal role of PXR associated with inflammation-drug and drug-drug interactions on DILI and highlighted the cautious clinical decision-making for pharmacotherapy to avoid DILI in the treatment of COVID-19 patients.
Collapse
Affiliation(s)
- Jingjing Huang
- Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Zhaokang Zhang
- Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Chenxia Hao
- Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Department of Pharmacy, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yuzhen Qiu
- Department of Critical Care, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Ruoming Tan
- Department of Critical Care, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jialin Liu
- Department of Critical Care, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Xiaoli Wang
- Department of Critical Care, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- *Correspondence: Xiaoli Wang, ; Wanhua Yang, ; Hongping Qu,
| | - Wanhua Yang
- Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- *Correspondence: Xiaoli Wang, ; Wanhua Yang, ; Hongping Qu,
| | - Hongping Qu
- Department of Critical Care, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- *Correspondence: Xiaoli Wang, ; Wanhua Yang, ; Hongping Qu,
| |
Collapse
|
|
20
|
Ghazanfar H, Kandhi S, Shin D, Muthumanickam A, Gurjar H, Qureshi ZA, Shaban M, Farag M, Haider A, Budhathoki P, Bhatt T, Ghazanfar A, Jyala A, Patel H. Impact of COVID-19 on the Gastrointestinal Tract: A Clinical Review. Cureus 2022; 14:e23333. [PMID: 35464519 PMCID: PMC9017282 DOI: 10.7759/cureus.23333] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/20/2022] [Indexed: 01/08/2023] Open
|
|
21
|
Chen J, Shu Q, Zhao ZY. Response to the outbreak of severe acute hepatitis of unknown origin in children. World J Pediatr 2022; 18:525-528. [PMID: 35739385 PMCID: PMC9223246 DOI: 10.1007/s12519-022-00577-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 05/30/2022] [Indexed: 11/27/2022]
Affiliation(s)
- Jie Chen
- National Clinical Research Center for Child Health, National Children's Regional Medical Center, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China
| | - Qiang Shu
- National Clinical Research Center for Child Health, National Children's Regional Medical Center, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China.
| | - Zheng-Yan Zhao
- National Clinical Research Center for Child Health, National Children's Regional Medical Center, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China.
| |
Collapse
|