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2.
Int J Mol Sci ; 23(9)2022 Apr 27.
Article in English | MEDLINE | ID: covidwho-1809943

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.


Subject(s)
Antiviral Agents , COVID-19 , Chemical and Drug Induced Liver Injury , Alanine Transaminase , Antiviral Agents/adverse effects , Aspartate Aminotransferases , COVID-19/drug therapy , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/epidemiology , Chemical and Drug Induced Liver Injury/etiology , Female , Humans , Male , Middle Aged , Publications
3.
World J Gastroenterol ; 27(48): 8370-8373, 2021 Dec 28.
Article in English | MEDLINE | ID: covidwho-1580314

ABSTRACT

Investigational treatments/drugs for coronavirus disease 2019 (COVID-19) have been applied, with repurposed or newly developed drugs, and their effectiveness has been evaluated. Some of these drugs may be hepatotoxic, and each monotherapy or combination therapy may increase the risk of drug-induced liver injury (DILI). We should aim to control dysregulation of liver function, as well as the progression of COVID-19, as much as possible. We discussed the potential risks of investigational treatments/drugs and promising drugs for both COVID-19 and DILI due to investigational treatments/drugs.


Subject(s)
COVID-19 , Chemical and Drug Induced Liver Injury , Chemical and Drug Induced Liver Injury/etiology , Drugs, Investigational/adverse effects , Humans , Liver , SARS-CoV-2 , Therapies, Investigational
5.
BMJ Case Rep ; 14(8)2021 Aug 17.
Article in English | MEDLINE | ID: covidwho-1361973

ABSTRACT

Hydralazine is a commonly prescribed antihypertensive agent. Some of its labelled adverse reactions include lupus-like syndrome, tachycardia, headache and fever. Despite its well-known side effects, little is known about hydralazine's hepatotoxic effects. We report the case of a 54-year-old female patient who was started on hydralazine for hypertension management but later presented with hydralazine-induced liver injury. Her initial presentation consisted of non-specific symptoms and a hepatocellular injury pattern. Liver biopsy revealed hepatic steatosis. Three weeks after discontinuation of hydralazine, the patient's liver enzymes normalised, and her symptoms resolved. Few studies have examined the incidence and mechanism by which hydralazine induces a liver injury pattern. With this case, we review the literature, the pathogenesis involved and the eventual management of hydralazine-induced liver injury. We propose close monitoring of liver enzymes for patients on hydralazine throughout their treatment course.


Subject(s)
Chemical and Drug Induced Liver Injury, Chronic , Chemical and Drug Induced Liver Injury , Hypertension , Antihypertensive Agents/adverse effects , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury, Chronic/drug therapy , Female , Humans , Hydralazine/adverse effects , Hypertension/drug therapy , Middle Aged
6.
Am J Case Rep ; 22: e932544, 2021 Aug 10.
Article in English | MEDLINE | ID: covidwho-1350539

ABSTRACT

BACKGROUND Fusarium spp. is a rare cause of opportunistic life-threatening fungal infections. It has a remarkably high resistance profile with few effective antifungal agents, mostly limited to voriconazole and liposomal amphotericin B. Drug-induced liver injury (DILI) by 1 of these 2 antifungal agents further complicates the management of these infections. CASE REPORT A 38-year-old woman with short bowel syndrome presented to the hospital with concerns of abdominal pain and loose stools. An abdominal CT was negative for inflammatory or ischemic bowel disease, and there was no evidence of liver disease. She tested positive for SARS-CoV-2 and required transfer to the ICU due to hypotension requiring fluid resuscitation and vasopressors. On day 43 of her admission, the patient developed a low-grade fever, for which she underwent central-line and peripheral-blood cultures that were positive for Fusarium dimerum. The central line was removed and i.v. voriconazole started. After 3 days of treatment, the patient's liver enzymes rose abruptly. Voriconazole was discontinued and replaced with liposomal amphotericin B, and the liver enzymes improved significantly. The patient completed 14 days of therapy and was discharged from the hospital. CONCLUSIONS This is a case of F. dimerum infection followed by DILI from voriconazole treatment. Her infection was resolved after switching to liposomal amphotericin B, with improvement in liver enzymes on day 1 after discontinuing voriconazole. This observation demonstrates that altering antifungal classes may be an appropriate strategy when confronted with DILI.


Subject(s)
COVID-19 , Chemical and Drug Induced Liver Injury , Fusarium , Sepsis , Adult , Amphotericin B/adverse effects , Antifungal Agents/adverse effects , Chemical and Drug Induced Liver Injury/etiology , Female , Humans , SARS-CoV-2 , Sepsis/drug therapy , Voriconazole/adverse effects
7.
Int J Clin Pharm ; 43(4): 1116-1122, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1333104

ABSTRACT

Background Liver injury has been documented independently in novel coronavirus disease 2019 (COVID-19) patients and patients treated with lopinavir-ritonavir. Objective to investigate the drug-induced liver injury associated with lopinavir-ritonavir among the patients with COVID-19. Methods We conducted a disproportionality analysis of US Food and Drug Administration Adverse Event Reporting System (FAERS) between 2020Q1 and 2021Q1 to evaluate the association between lopinavir-ritonavir and risk of drug-induced liver injury (or severe drug-induced liver injury) and calculated their reporting odds ratios (RORs) with 95% confidence intervals (CIs). Results A total of 3,425 cases of drug-induced liver injury were reported in 19,782 patients with COVID-19. The ROR for drug-induced liver injury was 2.99 (2.59-3.46), 3.16 (2.68-3.73), and 5.39 (4.63-6.26) when comparing lopinavir-ritonavir with all other drugs, hydroxychloroquine/chloroquine only, and remdesivir, respectively. For severe drug-induced liver injury, RORs for lopinavir-ritonavir provided evidence of an association compared with all other drugs (3.98; 3.15-5.05), compared with hydroxychloroquine/chloroquine only (5.33; 4.09-6.94), and compared with remdesivir (3.85; 3.03-4.89). Conclusions In the FAERS, we observed a disproportional signal for drug-induced liver injury associated with lopinavir-ritonavir in patients with COVID-19.


Subject(s)
Anti-HIV Agents/toxicity , COVID-19/complications , Chemical and Drug Induced Liver Injury/etiology , HIV Infections/complications , Lopinavir/toxicity , Ritonavir/toxicity , Adverse Drug Reaction Reporting Systems , Aged , Anti-HIV Agents/therapeutic use , Chemical and Drug Induced Liver Injury/epidemiology , Drug Combinations , Female , HIV Infections/virology , Humans , Lopinavir/therapeutic use , Male , Middle Aged , Ritonavir/therapeutic use , United States/epidemiology , United States Food and Drug Administration
8.
J Oncol Pharm Pract ; 28(2): 445-448, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1308070

ABSTRACT

INTRODUCTION: Favipiravir is an antiviral agent that is recently used for SARS-CoV2 infection. The drug-drug interactions of favipiravir especially with chemotherapeutic agents in a patient with malignancy are not well known. CASE REPORT: The patient diagnosed with metastatic osteosarcoma was given high dose methotrexate treatment, and favipiravir was started on the third day of the treatment with suspicion of SARS-CoV2 infection. Grade 3 hepatotoxicity developed after favipiravir.Management & outcome: The acute viral hepatitis panel and autoimmune liver disease panel were negative. The ultrasound of the abdomen was unremarkable for any hepatobiliary pathology. The all viral and hepatobiliary possible etiological factors were ruled out. The patient's liver enzymes increased just after (12 hours later) the initiation of favipiravir, and we diagnosed toxic hepatitis caused by favipiravir-methotrexate interaction. Therefore, methylprednisolone 1 mg/kg dose was started for a presumed diagnosis of toxic hepatitis. Hepatotoxicity completely regressed after favipiravir was discontinued. DISCUSSION: Favipiravir may inhibit methotrexate elimination by inhibiting aldehyde oxidase and its sequential use may cause hepatotoxicity in this case. The clinicians should keep in mind possible drug interactions while using new antiviral agents against SARS-CoV2 like favipiravir.


Subject(s)
Bone Neoplasms , COVID-19 , Chemical and Drug Induced Liver Injury , Osteosarcoma , Pharmaceutical Preparations , Amides , Antiviral Agents/therapeutic use , Bone Neoplasms/drug therapy , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/etiology , Humans , Methotrexate/adverse effects , Osteosarcoma/drug therapy , Pyrazines , RNA, Viral , SARS-CoV-2
9.
BMJ Open ; 11(7): e051484, 2021 07 09.
Article in English | MEDLINE | ID: covidwho-1304234

ABSTRACT

INTRODUCTION: COVID-19 is a highly infectious acute pneumonia. Glycyrrhizic acid preparation (GAP) has been found to have hepatoprotective and antiviral effects, but there is no supporting evidence on its efficacy and security for patients with COVID-19. METHODS AND ANALYSIS: The systematic review methods will be defined by Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This study will start on 1 July 2021 and end on 31 October 2021. A comprehensive electronic search will be conducted with the search of Web of Science, PubMed, Ovid web, China National Knowledge Infrastructure, Chinese Scientific and Journal Database, Wanfang Database and grey literature, and manual search will be conducted to search literature of randomised controlled trials, single-arm trials and retrospective studies about GAP in the treatment of anti-SARS-CoV-2 drug-induced liver injury from 1 December 2019 to 1 July 2021. There is no time limitations of publication and language will be restricted to Chinese and English. Retrieved studies will be independently screened by two researchers and relevant data will be extracted from studies. Interstudy heterogeneity will be assessed using the I2 statistic and explored through meta-regressions and subgroup analyses. Depending on data availability, we plan to conduct subgroup analyses by study population, geographical region and other selected clinical variables of interest. Quality assessment of the studies will be performed. Cochrane Handbook for Systematic Reviews of Interventions will be used to assess the risk of bias, and Grading of Recommendations Assessment, Development and Evaluation will be used to access the confidence in cumulative evidence. ETHICS AND DISSEMINATION: Ethical approval will not be required for no primary data of individual patients will be collected. The final report will be shared with the scientific community through publication in a peer-reviewed journal, as well as with key stakeholders, including patients, healthcare professionals and those working on COVID-19 research. PROSPERO REGISTRATION NUMBER: CRD42021234647.


Subject(s)
COVID-19 , Chemical and Drug Induced Liver Injury , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/etiology , China , Glycyrrhizic Acid , Humans , Meta-Analysis as Topic , Research Design , Retrospective Studies , SARS-CoV-2 , Systematic Reviews as Topic , Treatment Outcome
10.
Transfus Apher Sci ; 60(5): 103200, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1284583

ABSTRACT

Psoriasis is a chronic inflammatory skin disease that is characterized by well-demarcated erythematous plaques with a silver scale. Although many new and emerging therapeutic agents are often sufficient to control the disease, there is still a need for alternative treatment options in challenging cases. Extracorporeal photopheresis (ECP) has been applied to many T-cell-mediated diseases to restore immune homeostasis and treat psoriasis effectively. In this paper, we present a psoriasis patient who did not respond to methotrexate, narrowband ultraviolet B, or acitretin. Because of a diagnosis of non-Hodgkin lymphoma, the patient had contraindications for cyclosporine, fumaric acid esters, and biologics but achieved remission with a total of 12 sessions of ECP in two and a half months. Although exacerbation was recorded after polymerase chain reaction (PCR) confirmed coronavirus 2019 (COVID-19) disease infection at the end of the first month, scores from the psoriasis area severity index (PASI) and dermatological life quality index (DLQI) were regressed significantly within two and a half months. ECP seems to provide an effective and rapid response for psoriasis and should be considered for psoriasis patients who fail to respond or have contraindications to existing treatments.


Subject(s)
COVID-19/complications , Lymphoma, Non-Hodgkin/complications , Pandemics , Photopheresis , Psoriasis/drug therapy , SARS-CoV-2 , Acitretin/therapeutic use , Chemical and Drug Induced Liver Injury/etiology , Combined Modality Therapy , Contraindications, Drug , Cyclosporine/adverse effects , Humans , Male , Methotrexate/adverse effects , Methotrexate/therapeutic use , Middle Aged , Nails/pathology , Psoriasis/complications , Psoriasis/pathology , Psoriasis/radiotherapy , Quality of Life , Severity of Illness Index , Ultraviolet Therapy
11.
Clin Breast Cancer ; 22(1): e1-e7, 2022 01.
Article in English | MEDLINE | ID: covidwho-1252588

ABSTRACT

BACKGROUND: The coronavirus disease 2019 pandemic is a global public health event. Wuhan used to be the epicenter of China and finally controlled the outbreak through city lockdown and many other policies. However, the pandemic and the prevention strategies had a huge impact on the medical care procedures for patients with breast cancer, leading to the delay or interruption of anticancer therapies. PATIENTS AND METHODS: To better serve patients with breast cancer under the premise of epidemic control, many strategies have been proposed and optimized in our center. One of the most important parts of these strategies is the promotion of telemedicine, including online consultation, online prescription, and drug mailing services. RESULTS: In keeping with the city and hospital policies, we have also introduced stricter ward management policies and more precise care. CONCLUSION: Here, we collected the diagnosis and treatment process of patients with breast cancer in our center during the coronavirus disease 2019 pandemic, which was found to be correlated to a reduction in chemotherapy-related myelosuppression and hepatic dysfunction, hoping to provide a reference for other cancer centers that may suffer from the similar situation.


Subject(s)
Breast Neoplasms/drug therapy , COVID-19/epidemiology , SARS-CoV-2 , Adult , Aged , Antineoplastic Agents/adverse effects , Bone Marrow/drug effects , Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , Chemical and Drug Induced Liver Injury/etiology , China/epidemiology , Female , Humans , Middle Aged , Telemedicine
12.
Gastroenterol Hepatol ; 43(8): 472-480, 2020 Oct.
Article in English, Spanish | MEDLINE | ID: covidwho-1235898

ABSTRACT

The SARS-CoV-2 pandemic has proven to be a serious challenge for the Spanish healthcare system. The impact of the virus on the liver is not well known, but in patients with chronic liver disease, mostly in advanced stages, it can critically compromise survival and trigger decompensation. Treatment in this subpopulation is complex due to the potential hepatotoxicity of some of the medicinal products used. Moreover, the pandemic has also negatively impacted patients with liver disease who have not contracted COVID-19, since the reallocation of human and material resources to the care of patients with the virus has resulted in a decrease in the treatment, diagnosis and follow-up of patients with liver disease, which will surely have negative consequences in the near future. Efficient reorganization of hepatology units is a priority to minimise the impact of the pandemic on a population as vulnerable as liver disease patients.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Liver Diseases/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Age Factors , Alanine/adverse effects , Alanine/analogs & derivatives , Alanine/therapeutic use , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , Bile Ducts/virology , COVID-19 , Chemical and Drug Induced Liver Injury/etiology , Chronic Disease , Comorbidity , Coronavirus Infections/drug therapy , Disease Susceptibility , Gastroenterology/organization & administration , Health Resources/supply & distribution , Hepatitis, Chronic/drug therapy , Hepatitis, Chronic/epidemiology , Humans , Immunosuppressive Agents/adverse effects , Liver/drug effects , Liver/pathology , Liver/virology , Liver Function Tests , Liver Transplantation , Obesity/epidemiology , Resource Allocation , Risk Factors , SARS-CoV-2
13.
Am J Emerg Med ; 49: 441.e3-441.e4, 2021 11.
Article in English | MEDLINE | ID: covidwho-1213004

ABSTRACT

The U.S. Food and Drug Administration (FDA) recently issued an Emergency Use Authorization (EUA) for two highly effective Sars-CoV-2 (COVID-19) vaccines from Pfizer-BioNTech and Moderna. More recently, EUA was granted for the Johnson and Johnson COVID-19 vaccine which uses traditional virus-based technology. In this vaccine, researchers added the gene for the coronavirus spike protein to modified Adenovirus 26 and named it Ad26.COV2-S. Nearly 7 million doses of the Ad26.COV2-S have been administered as of mid-April 2021. Recently the Federal Drug Administration and Center for Disease Control and Prevention reviewed data involving six reported cases in the United States of cerebral venous sinus thrombosis in combination with thrombocytopenia in people who received the vaccination. All cases were in women between 18 and 48, with symptoms developing six to 13 days after vaccination. A recent study in the United Kingdom reported similar events in 23 patients age 21 to 77, 61% of which were female, with cases of presumed vaccine induced thrombosis and thrombocytopenia occurring six to 24 days after vaccination. We report a 62-year-old female who presented to the emergency department (ED) with acute onset of altered mental status. She had received the Ad26.COV2-S vaccine 37 days prior to ED presentation. She developed thrombotic thrombocytopenic purpura (TTP) and no other cause was found. To our knowledge this is the first case in the United States of thrombotic thrombocytopenic purpura after receiving the Ad26.COV2-S COVID-19 vaccine.


Subject(s)
Acute Kidney Injury/etiology , COVID-19 Vaccines/adverse effects , Chemical and Drug Induced Liver Injury/etiology , Purpura, Thrombotic Thrombocytopenic/etiology , Acute Kidney Injury/therapy , Chemical and Drug Induced Liver Injury/therapy , Female , Humans , Mental Disorders/etiology , Methylprednisolone/therapeutic use , Middle Aged , Plasma Exchange , Purpura, Thrombotic Thrombocytopenic/therapy , Renal Dialysis , Treatment Outcome
14.
Clin Infect Dis ; 72(7): 1256-1258, 2021 04 08.
Article in English | MEDLINE | ID: covidwho-1174888

ABSTRACT

We report a case of a man with COVID-19 who developed acute hepatotoxicity related to remdesivir with probable interaction of P-glycoprotein (P-gp) inhibitors. Until further details on this interaction become available, we recommend physicians to be cautious with the prescription of P-gp inhibitors in patients receiving remdesivir therapy.


Subject(s)
COVID-19 , Chemical and Drug Induced Liver Injury , ATP Binding Cassette Transporter, Subfamily B , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/adverse effects , COVID-19/drug therapy , Chemical and Drug Induced Liver Injury/etiology , Humans , Male , SARS-CoV-2
16.
Drug Saf ; 43(12): 1309-1314, 2020 12.
Article in English | MEDLINE | ID: covidwho-1092869

ABSTRACT

INTRODUCTION: In late 2019, a new coronavirus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-was discovered in Wuhan, China, and the World Health Organization later declared coronavirus disease 2019 (COVID-19) a pandemic. Numerous drugs have been repurposed and investigated for therapeutic effectiveness in the disease, including those from "Solidarity," an international clinical trial (azithromycin, chloroquine, hydroxychloroquine, the fixed combination lopinavir/ritonavir, and remdesivir). OBJECTIVE: Our objective was to evaluate adverse drug reaction (ADR) reporting for drugs when used in the treatment of COVID-19 compared with use for other indications, specifically focussing on sex differences. METHOD: We extracted reports on COVID-19-specific treatments from the global ADR database, VigiBase, using an algorithm developed to identify reports that listed COVID-19 as the indication. The Solidarity trial drugs were included, as were any drugs reported ≥ 100 times. We performed a descriptive comparison of reports for the same drugs used in non-COVID-19 indications. The data lock point date was 7 June 2020. RESULTS: In total, 2573 reports were identified for drugs used in the treatment of COVID-19. In order of frequency, the most reported ADRs were electrocardiogram QT-prolonged, diarrhoea, nausea, hepatitis, and vomiting in males and diarrhoea, electrocardiogram QT-prolonged, nausea, vomiting, and upper abdominal pain in females. Other hepatic and kidney-related events were included in the top ten ADRs in males, whereas no hepatic or renal terms were reported for females. COVID-19-related reporting patterns differed from non-pandemic reporting for these drugs. CONCLUSION: Review of a global database of suspected ADR reports revealed sex differences in the reporting patterns for drugs used in the treatment of COVID-19. Patterns of ADR sex differences need further elucidation.


Subject(s)
Antiviral Agents/adverse effects , COVID-19/drug therapy , Drug-Related Side Effects and Adverse Reactions/epidemiology , Abdominal Pain/chemically induced , Abdominal Pain/epidemiology , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/analogs & derivatives , Alanine/adverse effects , Alanine/analogs & derivatives , Antibodies, Monoclonal, Humanized/adverse effects , Azithromycin/adverse effects , Chemical and Drug Induced Liver Injury/epidemiology , Chemical and Drug Induced Liver Injury/etiology , Chloroquine/adverse effects , Databases, Pharmaceutical , Diarrhea/chemically induced , Diarrhea/epidemiology , Drug Combinations , Drug Eruptions/epidemiology , Drug Eruptions/etiology , Drug Repositioning , Female , Humans , Hydroxychloroquine/adverse effects , Long QT Syndrome/chemically induced , Long QT Syndrome/epidemiology , Lopinavir/adverse effects , Male , Nausea/chemically induced , Nausea/epidemiology , Oseltamivir/adverse effects , Ritonavir/adverse effects , Sex Distribution , Sex Factors , Vomiting/chemically induced , Vomiting/epidemiology
17.
Biomed Pharmacother ; 133: 111064, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1059802

ABSTRACT

COVID-19 is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early reported symptoms include fever, cough, and respiratory symptoms. There were few reports of digestive symptoms. However, with COVID-19 spreading worldwide, symptoms such as vomiting, diarrhoea, and abdominal pain have gained increasing attention. Research has found that angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 receptor, is strongly expressed in the gastrointestinal tract and liver. Whether theoretically or clinically, many studies have suggested a close connection between COVID-19 and the digestive system. In this review, we summarize the digestive symptoms reported in existing research, discuss the impact of SARS-CoV-2 on the gastrointestinal tract and liver, and determine the possible mechanisms and aetiology, such as cytokine storm. In-depth exploration of the relationship between COVID-19 and the digestive system is urgently needed.


Subject(s)
COVID-19/complications , Gastrointestinal Diseases/etiology , Liver Diseases/etiology , Pandemics , SARS-CoV-2/pathogenicity , Angiotensin-Converting Enzyme 2/metabolism , Anorexia/etiology , Antiviral Agents/adverse effects , Bile Ducts/metabolism , Bile Ducts/virology , COVID-19/epidemiology , COVID-19/immunology , COVID-19/pathology , Chemical and Drug Induced Liver Injury/etiology , Comorbidity , Cytokine Release Syndrome/etiology , Cytopathogenic Effect, Viral , Gastrointestinal Diseases/epidemiology , Gastrointestinal Microbiome , Gastrointestinal Tract/metabolism , Gastrointestinal Tract/pathology , Gastrointestinal Tract/virology , Humans , Immunosuppressive Agents/adverse effects , Liver/metabolism , Liver/pathology , Liver/virology , Liver Diseases/epidemiology , Liver Transplantation , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/virology , Postoperative Complications , Receptors, Virus/metabolism
18.
Drug Deliv ; 28(1): 325-342, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1057773

ABSTRACT

The aim of the present study was to investigate the pharmacological mechanism of matrine in treatment of COVID-19 combined with liver injury. Potential targets related to matrine, COVID-19 and liver injury were identified from several databases. We constructed PPI network and screened the core targets according to the degree value. Then, GO and KEGG enrichment were carried out. Molecular docking technology was used to verify the affinity between matrine and the crystal structure of core target protein. Finally, real-time RT-PCR was used to detect the effects of matrine on hub gene expression in liver tissue of liver injury mice and lung tissue of lung injury mice to further confirm the results of network pharmacological analysis. The results show that six core targets including AKT1, TP53, TNF, IL6, BCL2L1 and ATM were identified. The potential therapeutic mechanism of matrine on COVID-19 combined with liver injury is closely related to regulate antiviral process, improve immune system and regulate the level of inflammatory factors. Molecular docking showed that matrine could spontaneously bind to the receptor protein and had strong binding force. Real-time RT-PCR demonstrated that matrine could significantly reduce the expression of AKT1, TP53, TNF, IL6 and ATM in mice with liver injury or lung injury (P < 0.05), and increase the expression of BCL2L1 to a certain extent (P > 0.05). Our results indicate that matrine can achieve simultaneous intervention of COVID-19 combined with liver injury by multi-dimensional pharmacological mechanism.


Subject(s)
Alkaloids/pharmacology , COVID-19/drug therapy , COVID-19/epidemiology , Chemical and Drug Induced Liver Injury/epidemiology , Molecular Docking Simulation/methods , Quinolizines/pharmacology , Alkaloids/administration & dosage , Animals , Antiviral Agents/pharmacology , Chemical and Drug Induced Liver Injury/etiology , Dose-Response Relationship, Drug , Humans , Lipopolysaccharides/pharmacology , Liver/drug effects , Male , Mice , Mice, Inbred C57BL , Quinolizines/administration & dosage , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , Signal Transduction/drug effects
19.
BMJ Case Rep ; 14(1)2021 Jan 07.
Article in English | MEDLINE | ID: covidwho-1015617

ABSTRACT

Symptomatic drug-induced liver injury (DILI) is an uncommon problem. Direct DILI is dose-related, predictable with short latency (hour to days) and is generally associated with transient and reversible transaminitis without jaundice. Antimetabolites including methotrexate are a common cause for direct DILI. Hepatotoxicity associated with high-dose methotrexate (HD-MTX) is generally transient and includes reversible elevation of transaminase in up to 60% and associated hyperbilirubinaemia (≤grade 2) in 25% of courses and therefore is of no clinical significance. Severe grades of DILI with HD-MTX (grade ≥4) are extremely rare. We describe an adolescent with Burkitt leukaemia who had reversible grade 4 DILI including hyperbilirubinaemia postfirst course of HD-MTX. Rechallenge with two-third dose of HD-MTX in subsequent chemotherapeutic cycle did not cause recurrence of DILI.


Subject(s)
Antimetabolites, Antineoplastic/adverse effects , Burkitt Lymphoma/drug therapy , Chemical and Drug Induced Liver Injury/etiology , Hyperbilirubinemia/chemically induced , Methotrexate/adverse effects , Antimetabolites, Antineoplastic/administration & dosage , Child , Dose-Response Relationship, Drug , Humans , Male , Methotrexate/administration & dosage , Severity of Illness Index
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