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Wang X, Wang M, Cai M, Shao R, Xia G, Zhao W. Miriplatin-loaded liposome, as a novel mitophagy inducer, suppresses pancreatic cancer proliferation through blocking POLG and TFAM-mediated mtDNA replication. Acta Pharm Sin B 2023; 13:4477-4501. [PMID: 37969736 PMCID: PMC10638513 DOI: 10.1016/j.apsb.2023.07.009] [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: 04/19/2023] [Revised: 05/29/2023] [Accepted: 06/13/2023] [Indexed: 11/17/2023] Open
Abstract
Pancreatic cancer is a more aggressive and refractory malignancy. Resistance and toxicity limit drug efficacy. Herein, we report a lower toxic and higher effective miriplatin (MPt)-loaded liposome, LMPt, exhibiting totally different anti-cancer mechanism from previously reported platinum agents. Both in gemcitabine (GEM)-resistant/sensitive (GEM-R/S) pancreatic cancer cells, LMPt exhibits prominent anti-cancer activity, led by faster cellular entry-induced larger accumulation of MPt. The level of caveolin-1 (Cav-1) determines entry rate and switch of entry pathways of LMPt, indicating a novel role of Cav-1 in nanoparticle entry. After endosome-lysosome processing, in unchanged metabolite, MPt is released and targets mitochondria to enhance binding of mitochondria protease LONP1 with POLG and TFAM, to degrade POLG and TFAM. Then, via PINK1-Parkin axis, mitophagy is induced by POLG and TFAM degradation-initiated mitochondrial DNA (mtDNA) replication blocking. Additionally, POLG and TFAM are identified as novel prognostic markers of pancreatic cancer, and mtDNA replication-induced mitophagy blocking mediates their pro-cancer activity. Our findings reveal that the target of this liposomal platinum agent is mitochondria but not DNA (target of most platinum agents), and totally distinct mechanism of MPt and other formulations of MPt. Self-assembly offers LMPt special efficacy and mechanisms. Prominent action and characteristic mechanism make LMPt a promising cancer candidate.
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Affiliation(s)
- Xiaowei Wang
- State Key Laboratory of Respiratory Health and Multimorbidity, Key Laboratory of Antibiotic Bioengineering, Ministry of Health, Laboratory of Oncology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Pharmaceutics Department, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Mengyan Wang
- State Key Laboratory of Respiratory Health and Multimorbidity, Key Laboratory of Antibiotic Bioengineering, Ministry of Health, Laboratory of Oncology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Meilian Cai
- State Key Laboratory of Respiratory Health and Multimorbidity, Key Laboratory of Antibiotic Bioengineering, Ministry of Health, Laboratory of Oncology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Rongguang Shao
- State Key Laboratory of Respiratory Health and Multimorbidity, Key Laboratory of Antibiotic Bioengineering, Ministry of Health, Laboratory of Oncology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Guimin Xia
- Pharmaceutics Department, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Wuli Zhao
- State Key Laboratory of Respiratory Health and Multimorbidity, Key Laboratory of Antibiotic Bioengineering, Ministry of Health, Laboratory of Oncology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
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Doğan MF, Kaya K, Demirel HH, Başeğmez M, Şahin Y, Çiftçi O. The effect of vitamin C supplementation on favipiravir-induced oxidative stress and proinflammatory damage in livers and kidneys of rats. Immunopharmacol Immunotoxicol 2023; 45:521-526. [PMID: 36794622 DOI: 10.1080/08923973.2023.2181712] [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: 06/24/2022] [Accepted: 02/10/2023] [Indexed: 02/17/2023]
Abstract
Background: Favipiravir (FPV), an effective antiviral agent, is a drug used to treat influenza and COVID-19 by inhibiting the RNA-dependent RNA polymerase (RdRp) of RNA viruses. FPV has the potential to increase oxidative stress and organ damage. The purpose of this study was to demonstrate the oxidative stress and inflammation caused by FPV in the liver and kidneys of rats, as well as to investigate the curative effects of vitamin C (VitC).Methods: A total of 40 Sprague-Dawley male rats were randomly and equally divided into the following five groups: 1st; Control, 2nd; FPV = 20 mg/kg, 3rd; FPV = 100 mg/kg, 4th; FPV = 20 mg/kg + VitC (150 mg/kg), and 5th; FPV = 100 mg/kg + VitC (150 mg/kg) groups. Rats were given either FPV (orally) or FPV plus VitC (intramuscular) for 14 days. Rat blood, liver, and kidney samples were collected at 15 days to be analyzed for oxidative and histological changes.Results: FPV administration resulted in an increase in proinflammatory cytokines (TNF-α and IL-6) in the liver and kidney, as well as oxidative and histopathologic damage. FPV increased TBARS levels significantly (p < .05) and decreased GSH and CAT levels in liver and kidney tissues but had no effect on SOD activity. VitC supplementation significantly reduced TNF-a, IL-6, and TBARS levels while increasing GSH and CAT levels (p < .05). Furthermore, VitC significantly attenuated FPV-induced histopathological alterations associated with oxidative stress and inflammation in the liver and kidney tissues (p < .05).Conclusion: FPV caused liver and kidney damage in rats. In contrast, co-administration of FPV with VitC improved FPV-induced oxidative, pro-inflammatory, and histopathological changes.
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Affiliation(s)
- Muhammed Fatih Doğan
- Department of Pharmacology, Faculty of Medicine, Pamukkale University, Denizli, Turkey
| | - Kürşat Kaya
- Department of Biochemistry, Faculty of Medicine, Pamukkale University, Denizli, Turkey
| | - Hasan Hüseyin Demirel
- Department of Veterinary, Laboratory and Veterinary Health Program, Bayat Vocational High School, Afyon Kocatepe University, Afyonkarahisar, Turkey
| | - Mehmet Başeğmez
- Department of Veterinary, Laboratory and Veterinary Health Program, Acipayam Vocational High School, Pamukkale University, Denizli, Turkey
| | - Yasemin Şahin
- Department of Pharmacology, Faculty of Medicine, Pamukkale University, Denizli, Turkey
| | - Osman Çiftçi
- Department of Pharmacology, Faculty of Medicine, Pamukkale University, Denizli, Turkey
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Roshanshad R, Roshanshad A, Fereidooni R, Hosseini-Bensenjan M. COVID-19 and liver injury: Pathophysiology, risk factors, outcome and management in special populations. World J Hepatol 2023; 15:441-459. [PMID: 37206656 PMCID: PMC10190688 DOI: 10.4254/wjh.v15.i4.441] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 02/05/2023] [Accepted: 03/20/2023] [Indexed: 04/20/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 is an ongoing health concern. In addition to affecting the respiratory system, COVID-19 can potentially damage other systems in the body, leading to extra-pulmonary manifestations. Hepatic manifestations are among the common consequences of COVID-19. Although the precise mechanism of liver injury is still questionable, several mechanisms have been hypothesized, including direct viral effect, cytokine storm, hypoxic-ischemic injury, hypoxia-reperfusion injury, ferroptosis, and hepatotoxic medications. Risk factors of COVID-19-induced liver injury include severe COVID-19 infection, male gender, advanced age, obesity, and underlying diseases. The presentations of liver involvement comprise abnormalities in liver enzymes and radiologic findings, which can be utilized to predict the prognosis. Increased gamma-glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase levels with hypoalbuminemia can indicate severe liver injury and anticipate the need for intensive care units’ hospitalization. In imaging, a lower liver-to-spleen ratio and liver computed tomography attenuation may indicate a more severe illness. Furthermore, chronic liver disease patients are at a higher risk for severe disease and death from COVID-19. Nonalcoholic fatty liver disease had the highest risk of advanced COVID-19 disease and death, followed by metabolic-associated fatty liver disease and cirrhosis. In addition to COVID-19-induced liver injury, the pandemic has also altered the epidemiology and pattern of some hepatic diseases, such as alcoholic liver disease and hepatitis B. Therefore, it warrants special vigilance and awareness by healthcare professionals to screen and treat COVID-19-associated liver injury accordingly.
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Affiliation(s)
- Romina Roshanshad
- Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz 7184731443, Iran
| | | | - Reza Fereidooni
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
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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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Al-Shammari AH, Ali Shahadha MA. The effect of Favipiravir on liver enzyme among patients with mild to moderate COVID-19 infection: A prospective cohort study. JOURNAL OF POPULATION THERAPEUTICS AND CLINICAL PHARMACOLOGY = JOURNAL DE LA THERAPEUTIQUE DES POPULATIONS ET DE LA PHARMACOLOGIE CLINIQUE 2022; 29:e46-e54. [PMID: 36398597 DOI: 10.15586/jptcp.2022.967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Accepted: 10/11/2022] [Indexed: 06/16/2023]
Abstract
Teratogenicity and hyperuricemia are considered as the major adverse effects of favipiravir, but less is known about other possible side effects which includes drug-induced liver damage and renal injury. In the current research, assessment of favipiravir-induced liver injury was performed by evaluating liver enzymes among patients with mild to moderate COVID-19 infection. A prospective cohort study was conducted on 66 patients diagnosed with mild to moderate COVID-19 infection who were treated with favipiravir for 5 days. During this period, a baseline assessment of liver enzymes (aspartate aminotransferase - AST, alanine transaminase - ALT and alkaline phosphatase - ALP) in addition to bilirubin before initiation of therapy and after 1 day of completion of therapy were carried out. The comparison of all measured parameters among all patients before and after receiving the treatment showed that non-significant differences were obtained in their levels. It was noticed that COVID-19 patients demonstrated high AST levels in which only 16 patients out of the all-subjected cases (66 patients) had AST levels of less than 45 U/L whereas the majority of patients showed normal ALT, ALP, and bilirubin levels. It was concluded that 5 days administration of favipiravir in mild to moderate COVID-19 patients who had no previous liver diseases did not affect the liver enzymes significantly and only transient elevations were occurred.
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Kulkarni AV, Khelgi A, Sekaran A, Reddy R, Sharma M, Tirumalle S, Gora BA, Somireddy A, Reddy J, Menon B, Reddy DN, Rao NP. Post-COVID-19 Cholestasis: A Case Series and Review of Literature. J Clin Exp Hepatol 2022; 12:1580-1590. [PMID: 35719861 PMCID: PMC9187855 DOI: 10.1016/j.jceh.2022.06.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 06/06/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Coronavirus disease-2019 (COVID-19) cholangiopathy is a recently known entity. There are very few reports of liver transplantation (LT) for COVID-19-induced cholangiopathy. It is well known that vaccines can prevent severe disease and improve outcomes. However, there are no reports on the impact of COVID-19 vaccines on cholestasis. Therefore, we aimed to compare the course and outcome of patients who developed cholestasis following COVID-19 infection among vaccinated and unvaccinated individuals. Methods: Patients diagnosed with post-COVID cholestasis during the pandemic were included in the study after excluding other causes of cholestasis. RESULTS Eight unvaccinated and seven vaccinated individuals developed cholestasis following COVID-19 infection. Baseline demographics, presentation, severity, and management of COVID-19 were similar in both groups. However, patients in the unvaccinated group had a protracted course. The peak ALP was 312 (239-517) U/L in the vaccinated group and 571.5 (368-1058) U/L in the unvaccinated group (P = 0.02). Similarly, the peak γ-glutamyl transpeptidase values were lower in the vaccinated (325 [237-600] U/L) than in the unvaccinated group (832 [491-1640] U/L; P = 0.004). However, the peak values of total bilirubin, transaminases, and INR were similar in both groups. Five patients developed ascites gradually in the unvaccinated group whereas none in the vaccinated group developed ascites. Plasma exchange was done in five patients, and two were successfully bridged to living donor LT in the unvaccinated group. Only two patients recovered with conservative management in the unvaccinated group, whereas all recovered with conservative management in the vaccinated group. The other four patients in the unvaccinated group were planned for LT. CONCLUSION Post-COVID-19 cholestasis is associated with high morbidity and mortality, meriting early identification and appropriate management. Vaccination can modify the course of severe COVID-19 infection and improve outcomes.
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Key Words
- ALP, alkaline phosphatase
- ALT, alanine transaminase
- AST, aspartate transaminase
- COVID-19, coronavirus disease-2019
- DDLT, deceased donor living transplantation
- GGT, γ-glutamyl transpeptidase
- LDLT, living donor liver transplantation
- SARS-CoV-2, severe acute respiratory syndrome coronavirus 2
- UDCA, ursodeoxycholic acid
- ULN, upper limit of normal
- liver function test
- liver transplantation
- plasma exchange
- vaccination
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Affiliation(s)
| | - Amit Khelgi
- Department of Microbiology, K S Hegde Medical Academy, Mangalore, India
| | | | - Raghuram Reddy
- Department of Liver Transplantation, AIG Hospitals, Hyderabad, India
| | - Mithun Sharma
- Department of Hepatology, AIG Hospitals, Hyderabad, India
| | | | - Baqar A. Gora
- Department of Hepatology, AIG Hospitals, Hyderabad, India
| | | | - Jignesh Reddy
- Department of Radiology, AIG Hospitals, Hyderabad, India
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Mihai N, Tiliscan C, Visan CA, Stratan L, Ganea O, Arama SS, Lazar M, Arama V. Evaluation of Drug-Induced Liver Injury in Hospitalized Patients with SARS-CoV-2 Infection. Microorganisms 2022; 10:microorganisms10102045. [PMID: 36296321 PMCID: PMC9606929 DOI: 10.3390/microorganisms10102045] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 09/17/2022] [Accepted: 10/13/2022] [Indexed: 11/25/2022] Open
Abstract
Elevated liver enzymes are frequently reported in SARS-CoV-2-infected patients. Several mechanisms of liver injury have been proposed, but no clear conclusions were drawn. We aimed to evaluate hepatocellular and cholestatic injury in relation to the administration of potentially hepatotoxic drugs included in the current COVID-19 therapeutic guidelines in a retrospective cohort of 396 hospitalized COVID-19 patients. The main findings of our study are: (1) Significant increase in aminotransferases level was observed during hospitalization, suggesting drug-related hepatotoxicity. (2) Tocilizumab was correlated with hepatocellular injury, including ALT values greater than five times the upper limit of normal. (3) Anakinra was correlated with ALT values greater than three times the upper limit of normal. (4) Younger patients receiving tocilizumab or anakinra had a higher risk of hepatocellular injury. (5) The combination of favipiravir with tocilizumab was associated with AST values greater than three times the upper limit of normal and with an increase in direct bilirubin. (6) The administration of at least three potentially hepatotoxic drugs was correlated with hepatocellular injury, including ALT values greater than five times the upper limit of normal, and with the increase in indirect bilirubin. (7) Remdesivir and favipiravir by themselves did not correlate with hepatocellular or cholestatic injury in our study cohort.
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Affiliation(s)
- Nicoleta Mihai
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania
- “Prof. Dr. Matei Bals” National Institute for Infectious Diseases, 1 Calistrat Grozovici Street, 021105 Bucharest, Romania
| | - Catalin Tiliscan
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania
- “Prof. Dr. Matei Bals” National Institute for Infectious Diseases, 1 Calistrat Grozovici Street, 021105 Bucharest, Romania
- Correspondence:
| | - Constanta Angelica Visan
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania
- “Prof. Dr. Matei Bals” National Institute for Infectious Diseases, 1 Calistrat Grozovici Street, 021105 Bucharest, Romania
| | - Laurentiu Stratan
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania
- “Prof. Dr. Matei Bals” National Institute for Infectious Diseases, 1 Calistrat Grozovici Street, 021105 Bucharest, Romania
| | - Oana Ganea
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania
- “Prof. Dr. Matei Bals” National Institute for Infectious Diseases, 1 Calistrat Grozovici Street, 021105 Bucharest, Romania
| | - Stefan Sorin Arama
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania
- “Prof. Dr. Matei Bals” National Institute for Infectious Diseases, 1 Calistrat Grozovici Street, 021105 Bucharest, Romania
| | - Mihai Lazar
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania
- “Prof. Dr. Matei Bals” National Institute for Infectious Diseases, 1 Calistrat Grozovici Street, 021105 Bucharest, Romania
| | - Victoria Arama
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania
- “Prof. Dr. Matei Bals” National Institute for Infectious Diseases, 1 Calistrat Grozovici Street, 021105 Bucharest, Romania
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Liver Injury in COVID-19 Patients with Drugs as Causatives: A Systematic Review of 996 DILI Cases Published 2020/2021 Based on RUCAM as Causality Assessment Method. Int J Mol Sci 2022; 23:ijms23094828. [PMID: 35563242 PMCID: PMC9100611 DOI: 10.3390/ijms23094828] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 04/04/2022] [Accepted: 04/20/2022] [Indexed: 02/06/2023] Open
Abstract
Patients with coronavirus disease 19 (COVID-19) commonly show abnormalities of liver tests (LTs) of undetermined cause. Considering drugs as tentative culprits, the current systematic review searched for published COVID-19 cases with suspected drug-induced liver injury (DILI) and established diagnosis using the diagnostic algorithm of RUCAM (Roussel Uclaf Causality Assessment Method). Data worldwide on DILI cases assessed by RUCAM in COVID-19 patients were sparse. A total of 6/200 reports with initially suspected 996 DILI cases in COVID-19 patients and using all RUCAM-based DILI cases allowed for a clear description of clinical features of RUCAM-based DILI cases among COVID-19 patients: (1) The updated RUCAM published in 2016 was equally often used as the original RUCAM of 1993, with both identifying DILI and other liver diseases as confounders; (2) RUCAM also worked well in patients treated with up to 18 drugs and provided for most DILI cases a probable or highly probable causality level for drugs; (3) DILI was preferentially caused by antiviral drugs given empirically due to their known therapeutic efficacy in other virus infections; (4) hepatocellular injury was more often reported than cholestatic or mixed injury; (5) maximum LT values were found for alanine aminotransferase (ALT) 1.541 U/L and aspartate aminotransferase (AST) 1.076 U/L; (6) the ALT/AST ratio was variable and ranged from 0.4 to 1.4; (7) the mean or median age of the COVID-19 patients with DILI ranged from 54.3 to 56 years; (8) the ratio of males to females was 1.8–3.4:1; (9) outcome was favorable for most patients, likely due to careful selection of the drugs and quick cessation of drug treatment with emerging DILI, but it was fatal in 19 patients; (10) countries reporting RUCAM-based DILI cases in COVID-19 patients included China, India, Japan, Montenegro, and Spain; (11) robust estimation of the percentage contribution of RUCAM-based DILI for the increased LTs in COVID-19 patients is outside of the current scope. In conclusion, RUCAM-based DILI with its clinical characteristics in COVID-19 patients and its classification as a confounding variable is now well defined, requiring a new correct description of COVID-19 features by removing DILI characteristics as confounders.
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Ozkurt Z, Çınar Tanrıverdi E. COVID-19: Gastrointestinal manifestations, liver injury and recommendations. World J Clin Cases 2022; 10:1140-1163. [PMID: 35211548 PMCID: PMC8855202 DOI: 10.12998/wjcc.v10.i4.1140] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 06/28/2021] [Accepted: 12/23/2021] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) has caused a pandemic that affected all countries with nearly 270 million patients and 5 million deaths, as of as of December, 2021. The severe acute respiratory syndrome coronavirus 2 virus targets the receptor, angiotensin-converting enzyme 2, which is frequently found in human intestinal epithelial cells, bile duct epithelial cells, and liver cells, and all gastrointestinal system organs are affected by COVID-19 infection. The aim of this study is to review the gastrointestinal manifestations and liver damage of COVID-19 infection and investigate the severe COVID-19 infection risk in patients that have chronic gastrointestinal disease, along with current treatment guidelines. A literature search was conducted on electronic databases of PubMed, Scopus, and Cochran Library, consisting of COVID-19, liver injury, gastrointestinal system findings, and treatment. Liver and intestinal involvements are the most common manifestations. Diarrhea, anorexia, nausea/vomiting, abdominal pain are the most frequent symptoms seen in intestinal involvement. Mild hepatitis occurs with elevated levels of transaminases. Gastrointestinal involvement is associated with long hospital stay, severity of the disease, and intensive care unit necessity. Treatments and follow-up of patients with inflammatory bowel diseases, cirrhosis, hepatocellular carcinoma, or liver transplant have been negatively affected during the pandemic. Patients with cirrhosis, hepatocellular carcinoma, auto-immune diseases, or liver transplantation may have a greater risk for severe COVID-19. Diagnostic or therapeutic procedures should be restricted with specific conditions. Telemedicine should be used in non-urgent periodic patient follow up. COVID-19 treatment should not be delayed in patients at the risk group. COVID-19 vaccination should be prioritized in this group.
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Affiliation(s)
- Zulal Ozkurt
- Department of Infectious Disease, Atatürk University, School of Medicine, Erzurum 25100, Turkey
| | - Esra Çınar Tanrıverdi
- Department of Medical Education, Atatürk University, School of Medicine, Erzurum 25100, Turkey
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