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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.
BMJ Case Rep ; 15(3)2022 Mar 22.
Article in English | MEDLINE | ID: covidwho-1759312

ABSTRACT

Hepatitis-associated aplastic anaemia (HAAA) is a rare condition characterised by onset of acute hepatitis which is followed by development of severe pancytopenia due to bone marrow failure within 6 months. This syndrome can be precipitated by acute viral infections, but the aetiology remains unknown in the majority. Drug-induced HAAA is extremely rare and has been reported with nutritional and dietary supplements in current literature. We report the first cases of ayurvedic herbal and homeopathic remedies-associated HAAA in two patients which proved fatal in both. Evaluation of patients with acute hepatitis and severe pancytopenia must include a detailed evaluation for complementary and alternative medicine use.


Subject(s)
Anemia, Aplastic , Chemical and Drug Induced Liver Injury , Gymnema sylvestre , Hepatitis , Materia Medica , Anemia, Aplastic/chemically induced , Anemia, Aplastic/therapy , Chemical and Drug Induced Liver Injury/complications , Chemical and Drug Induced Liver Injury/therapy , Hepatitis/complications , Humans , Materia Medica/adverse effects
4.
Rev Esp Enferm Dig ; 114(5): 297-298, 2022 05.
Article in English | MEDLINE | ID: covidwho-1633201

ABSTRACT

We present the case of a 56-year-old female admitted to our centre for hepatitis. She had recieved the first dose of the BNT162b2 vaccine against SARS-CoV-2 10 days before the admission. Etiologic study was negative. The patient was diagnosed with vaccine-induced hepatitis.


Subject(s)
COVID-19 , Chemical and Drug Induced Liver Injury , Hepatitis , /adverse effects , COVID-19/prevention & control , Female , Humans , Middle Aged
5.
Int J Biochem Cell Biol ; 143: 106138, 2022 02.
Article in English | MEDLINE | ID: covidwho-1588223

ABSTRACT

Nicotinic acetylcholine receptors mediate fast synaptic transmission in neuro-muscular junctions and autonomic ganglia and modulate survival, proliferation and neurotransmitter or cytokine release in the brain and non-excitable cells. The neuronal-type nicotinic acetylcholine receptors are expressed in the outer mitochondria membrane to regulate the release of pro-apoptotic substances like cytochrome c or reactive oxygen species. In the intracellular environment, nicotinic acetylcholine receptor signaling is ion-independent and triggers intramitochondrial kinases, similar to those activated by plasma membrane nicotinic acetylcholine receptors. The present review will describe the data obtained during the last five years including, in particular, post-translational glycosylation as a targeting signal to mitochondria, mechanisms of mitochondrial nicotinic acetylcholine receptor signaling studied with subtype-specific agonists, antagonists, positive allosteric modulators and knockout mice lacking certain nicotinic acetylcholine receptor subunits, interaction of mitochondrial nicotinic acetylcholine receptors with Bcl-2 family proteins and their involvement in important pathologies like neuroinflammation, liver damage and SARS-CoV-2 infection.


Subject(s)
COVID-19/genetics , Chemical and Drug Induced Liver Injury/genetics , Mitochondria/genetics , Proto-Oncogene Proteins c-bcl-2/genetics , Receptors, Nicotinic/genetics , Allosteric Regulation , Animals , COVID-19/metabolism , COVID-19/pathology , COVID-19/virology , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Disease Models, Animal , Humans , Mice , Mitochondria/metabolism , /pathology , Nicotinic Agonists/pharmacology , Nicotinic Antagonists/pharmacology , Protein Processing, Post-Translational , Proto-Oncogene Proteins c-bcl-2/metabolism , Receptors, Nicotinic/metabolism , SARS-CoV-2/pathogenicity , Signal Transduction , Voltage-Dependent Anion Channel 1/genetics , Voltage-Dependent Anion Channel 1/metabolism
6.
Int Immunopharmacol ; 103: 108463, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1587490

ABSTRACT

Therapeutics that impair the innate immune responses of the liver during the inflammatory cytokine storm like that occurring in COVID-19 are greatly needed. Much interest is currently directed toward Janus kinase (JAK) inhibitors as potential candidates to mitigate this life-threatening complication. Accordingly, this study investigated the influence of the novel JAK inhibitor ruxolitinib (RXB) on concanavalin A (Con A)-induced hepatitis and systemic hyperinflammation in mice to simulate the context occurring in COVID-19 patients. Mice were orally treated with RXB (75 and 150 mg/kg) 2 h prior to the intravenous administration of Con A (20 mg/kg) for a period of 12 h. The results showed that RXB pretreatments were efficient in abrogating Con A-instigated hepatocellular injury (ALT, AST, LDH), necrosis (histopathology), apoptosis (cleaved caspase-3) and nuclear proliferation due to damage (PCNA). The protective mechanism of RXB were attributed to i) prevention of Con A-enhanced hepatic production and systemic release of the proinflammatory cytokines TNF-α, IFN-γ and IL-17A, which coincided with decreasing infiltration of immune cells (monocytes, neutrophils), ii) reducing Con A-induced hepatic overexpression of IL-1ß and CD98 alongside NF-κB activation, and iii) lessening Con A-induced consumption of GSH and GSH peroxidase and generation of oxidative stress products (MDA, 4-HNE, NOx) in the liver. In summary, JAK inhibition by RXB led to eminent protection of the liver against Con A-deleterious manifestations primarily via curbing the inflammatory cytokine storm driven by TNF-α, IFN-γ and IL-17A.


Subject(s)
Concanavalin A/toxicity , Cytokine Release Syndrome/chemically induced , Cytokine Release Syndrome/drug therapy , Nitriles/pharmacology , Pyrazoles/pharmacology , Pyrimidines/pharmacology , Aldehydes/metabolism , Animals , Chemical and Drug Induced Liver Injury , Dose-Response Relationship, Drug , Inflammation/chemically induced , Liver/drug effects , Liver/metabolism , Male , Malondialdehyde/metabolism , Mice , Mice, Inbred BALB C , Nitrates/metabolism , Nitriles/administration & dosage , Nitrites/metabolism , Oxidative Stress , Peroxidase/metabolism , Pyrazoles/administration & dosage , Pyrimidines/administration & dosage
7.
Int J Mol Sci ; 23(1)2021 Dec 22.
Article in English | MEDLINE | ID: covidwho-1580701

ABSTRACT

Using drugs to treat COVID-19 symptoms may induce adverse effects and modify patient outcomes. These adverse events may be further aggravated in obese patients, who often present different illnesses such as metabolic-associated fatty liver disease. In Rennes University Hospital, several drug such as hydroxychloroquine (HCQ) have been used in the clinical trial HARMONICOV to treat COVID-19 patients, including obese patients. The aim of this study is to determine whether HCQ metabolism and hepatotoxicity are worsened in obese patients using an in vivo/in vitro approach. Liquid chromatography high resolution mass spectrometry in combination with untargeted screening and molecular networking were employed to study drug metabolism in vivo (patient's plasma) and in vitro (HepaRG cells and RPTEC cells). In addition, HepaRG cells model were used to reproduce pathophysiological features of obese patient metabolism, i.e., in the condition of hepatic steatosis. The metabolic signature of HCQ was modified in HepaRG cells cultured under a steatosis condition and a new metabolite was detected (carboxychloroquine). The RPTEC model was found to produce only one metabolite. A higher cytotoxicity of HCQ was observed in HepaRG cells exposed to exogenous fatty acids, while neutral lipid accumulation (steatosis) was further enhanced in these cells. These in vitro data were compared with the biological parameters of 17 COVID-19 patients treated with HCQ included in the HARMONICOV cohort. Overall, our data suggest that steatosis may be a risk factor for altered drug metabolism and possibly toxicity of HCQ.


Subject(s)
Antiviral Agents/adverse effects , Antiviral Agents/metabolism , COVID-19/drug therapy , Hydroxychloroquine/adverse effects , Hydroxychloroquine/metabolism , Aged , Antiviral Agents/therapeutic use , COVID-19/complications , COVID-19/metabolism , Cell Line , Cell Survival/drug effects , Chemical and Drug Induced Liver Injury/metabolism , Correlation of Data , Drug-Related Side Effects and Adverse Reactions , Fatty Acids/pharmacology , Fatty Liver/complications , Fatty Liver/metabolism , Female , Humans , Hydroxychloroquine/therapeutic use , Linear Models , Male , Metabolic Networks and Pathways , Middle Aged , Obesity/complications , Obesity/metabolism , Risk Factors
8.
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
9.
Rev. Ciênc. Méd. Biol. (Impr.) ; 19(3): 449-456, dez 5, 2020. fig
Article in Portuguese | WHO COVID, LILACS (Americas) | ID: covidwho-1502769

ABSTRACT

Introdução: o fármaco ranelato de estrôncio (RE) é muito utilizado na terapêutica profilática e no controle da osteoporose. Age sistemicamente diminuindo a reabsorção e aumentando a formação óssea, apresentando eventos adversos pouco esclarecidos na literatura, à exemplo a síndrome DRESS com envolvimento hepático. Objetivo: avaliar a morfologia hepática em ratos norvegicus albinus após administração do RE. Metodologia: estudo experimental com 10 ratos, divididos aleatoriamente em dois grupos, Grupo Controle (GC), sem administração do RE, e Grupo Ranelato de Estrôncio (GRE), ambos acompanhados durante 15 dias, e, em seguida, sacrificados e o fígado de cada animal colocado para fixação no solução de formaldeído a 4% durante 48 horas. Após essa etapa, foram realizados os procedimentos necessários à análise pela microscopia óptica, com lâminas coradas pela hematoxilina e eosina, e picrosirius red.Resultados: nos GC e GRE foram encontradas alterações similares, como reação ductular, dilatação sinusoidal e fibrose perissinusoidal, com intensidades distintas entre os grupos, sendo a reação ductular mais proeminente no GC, e a dilatação sinusoidal e fibrose perissinusoidal mais pronunciada no GRE. Além disso, no GC foram evidenciados achados inflamatórios, como presença de infiltrado inflamatório misto e hiperplasia de células de Kupffer, não visualizados no GRE, implicando numa possível ação anti-inflamatória do RE. Conclusão: pode-se concluir que foram visualizadas diferenças nos achados morfológicos do parênquima hepático dos ratos tratados com o RE em comparação aos não tratados, ainda que esses achados não sejam suficientes para inferir a incidência de um processo patológico característico, como cirrose ou hepatite.


Introduction: the drug strontium ranelate (SR) is widely used in prophylactic therapy and in the control of osteoporosis. It acts by reducing reabsorption and increasing bone formation systemically, presenting unclear adverse events in the literature, such as the DRESS syndrome with hepatic involvement. Objective: to evaluate hepatic morphology in norvegicus albinus rats after SR administration. Methodology: experimental group with 10 rats, divided into two groups, randomly distributed, five from the Control Group (CG), without SR administration, and the other five from the Strontium Ranelate Group (SRG), both followed for 15 days, and then sacrificed and the liver of each animal placed for fixation in 4% formalin for 48 hours. After this step, the procedures necessary for the analysis by optical microscopy were performed, with blades stained by hematoxylin e eosin, and picrosirius red. Results: in CG and SRG, similar alterations were observed, such as ductular reaction, sinusoidal dilatation and perissinusoidal fibrosis, with distinct intensities between the groups, being the ductular reaction more prominent in the CG, and sinusoidal dilation and a perissinusoidal fibrosis more pronounced in the SRG. In addition, in the CG were evidenced inflammatory findings such as the presence of mixed inflammatory infiltrate and Kupffer cell hyperplasia, not visualized in the SRG, implying a possible anti-inflammatory action of SR. Conclusion: it can be concluded that differences were observed in the morphological findings of the hepatic parenchyma of rats treated with SR compared to untreated rats, although these findings are not sufficient to infer the incidence of a characteristic pathological process, such as cirrhosis or hepatitis.


Subject(s)
Animals , Male , Rats , Rats , Pharmaceutical Preparations , Chemical and Drug Induced Liver Injury , Rats, Inbred Strains
10.
Ann Rheum Dis ; 80(11): 1376-1384, 2021 11.
Article in English | MEDLINE | ID: covidwho-1462911

ABSTRACT

OBJECTIVES: There are no head-to-head trials of different dose escalation strategies of methotrexate (MTX) in RA. We compared the efficacy, safety and tolerability of 'usual' (5 mg every 4 weeks) versus 'fast' (5 mg every 2 weeks) escalation of oral MTX. METHODS: This multicentre, open-label (assessor blinded) RCT included patients 18-55 years of age having active RA with disease duration <5 years, and not on DMARDs. Patients were randomized 1:1 into usual or fast escalation groups, both groups starting MTX at 15 mg/week till a maximum of 25 mg/week. Primary outcome was EULAR good response at 16 weeks, secondary outcomes were ΔDAS28 and adverse effects (AE). Analyses were intention-to-treat. RESULTS: 178 patients with mean DAS28-CRP of 5.4(1.1) were randomized to usual (n=89) or fast escalation groups (n=89). At 16 weeks, there was no difference in good EULAR response in the usual (28.1%) or fast escalation (22.5%) groups (p=0.8). There was no difference in mean ΔDAS28-CRP at 8 weeks (-0.9, -0.8, p=0.72) or 16 weeks (-1.3, -1.3, p=0.98). Even at 24 weeks (extended follow-up), responses were similar. There were no inter-group differences in ΔHAQ, or MTX-polyglutamates 1-3 levels at 8 or 16 weeks. Gastrointestinal AE were higher in the fast escalation group over initial 8 weeks (27%, 40%, p=0.048), but not over 16 weeks. There was no difference in cytopenias, transaminitis, or drug discontinuation/dose reduction between the groups. No serious AE were seen. CONCLUSION: A faster MTX escalation strategy in RA was not more efficacious over 16-24 weeks, and did not significantly increase AE, except higher gastrointestinal AE initially. TRIAL REGISTRATION NUMBER: CTRI/2018/12/016549.


Subject(s)
Antirheumatic Agents/administration & dosage , Arthritis, Rheumatoid/drug therapy , Methotrexate/administration & dosage , Adolescent , Adult , Arthritis, Rheumatoid/physiopathology , Chemical and Drug Induced Liver Injury/epidemiology , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Gastrointestinal Diseases/chemically induced , Gastrointestinal Diseases/epidemiology , Humans , Leukopenia/chemically induced , Leukopenia/epidemiology , Male , Methotrexate/analogs & derivatives , Methotrexate/blood , Middle Aged , Polyglutamic Acid/analogs & derivatives , Polyglutamic Acid/blood , Thrombocytopenia/chemically induced , Thrombocytopenia/epidemiology , Treatment Outcome , Young Adult
11.
Lipids Health Dis ; 20(1): 126, 2021 Oct 03.
Article in English | MEDLINE | ID: covidwho-1448237

ABSTRACT

The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). At present, the COVID-19 has been prevalent worldwide for more than a year and caused more than four million deaths. Liver injury was frequently observed in patients with COVID-19. Recently, a new definition of metabolic dysfunction associated fatty liver disease (MAFLD) was proposed by a panel of international experts, and the relationship between MAFLD and COVID-19 has been actively investigated. Several previous studies indicated that the patients with MAFLD had a higher prevalence of COVID-19 and a tendency to develop severe type of respiratory infection, and others indicated that liver injury would be exacerbated in the patients with MAFLD once infected with COVID-19. The mechanism underlying the relationship between MAFLD and COVID-19 infection has not been thoroughly investigated, and recent studies indicated that multifactorial mechanisms, such as altered host angiotensin converting enzyme 2 (ACE2) receptor expression, direct viral attack, disruption of cholangiocyte function, systemic inflammatory reaction, drug-induced liver injury, hepatic ischemic and hypoxic injury, and MAFLD-related glucose and lipid metabolic disorders, might jointly contribute to both of the adverse hepatic and respiratory outcomes. In this review, we discussed the relationship between MAFLD and COVID-19 based on current available literature, and summarized the recommendations for clinical management of MAFLD patients during the pandemic of COVID-19.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/complications , Chemical and Drug Induced Liver Injury/complications , Hypoxia/complications , Liver/metabolism , Non-alcoholic Fatty Liver Disease/complications , SARS-CoV-2/pathogenicity , Age Factors , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/drug therapy , COVID-19/pathology , COVID-19/virology , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury/virology , Cytokines/genetics , Cytokines/metabolism , Dipeptides/therapeutic use , Gene Expression Regulation , Glucose/metabolism , Glycyrrhizic Acid/therapeutic use , Humans , Hypoxia/drug therapy , Hypoxia/pathology , Hypoxia/virology , Liver/drug effects , Liver/pathology , Liver/virology , Lung/drug effects , Lung/metabolism , Lung/pathology , Lung/virology , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/virology , Receptors, Virus/genetics , Receptors, Virus/metabolism , Severity of Illness Index
12.
Bratisl Lek Listy ; 122(10): 732-738, 2021.
Article in English | MEDLINE | ID: covidwho-1441311

ABSTRACT

BACKGROUND: The use of acetaminophen (APAP) is increasing recently, especially with COVID-19 outbreaks. APAP is safe at therapeutic levels, however, an overdose can cause severe liver injury. This study aims to explore possible mechanisms involved in APAP­induced hepatotoxicity and compare different hepatoprotective agents, namely vitamin E, hydrogen sulfide (H2S) and necrostatin-1 (NEC-1). METHODS: Adult male albino rats were divided into groups: Control group, APAP­induced hepatotoxicity group, Vitamin E­treated group, H2S­treated group and NEC-1­treated group. Serum levels for aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin-33 (IL-33), tumor necrosis factor alpha (TNF-α), reduced glutathione (GSH) and lipid profile were measured. Histopathological examinations of liver tissue with H(et)E stain and immunohistochemistry for activated caspase-3 were also done. RESULTS: APAP­treated group showed elevated liver transaminases, hyperlipidemia, and deficient liver anti-oxidative response together with disturbed hepatic architecture and increased immune-expression of activated caspase-3 in hepatic tissue. Pretreatment with vitamin E, H2S or NEC-1 reversed the affected parameters. Vitamin E and H2S showed greater improvement when compared to NEC-1. CONCLUSION: Vitamin E, H2S and NEC-1 showed protective effects against APAP-induced hepatotoxicity, thus they may be used as an adjuvant therapy when APAP is indicated for long periods as is the case in COVID-19 patients (Tab. 2, Fig. 2, Ref. 45). Text in PDF www.elis.sk Keywords: acetaminophen, hepatotoxicity, apoptosis, necrostatin-1, vitamin E, H2S.


Subject(s)
COVID-19 , Chemical and Drug Induced Liver Injury , Hydrogen Sulfide , Acetaminophen/toxicity , Alanine Transaminase/metabolism , Animals , Aspartate Aminotransferases/metabolism , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/prevention & control , Humans , Hydrogen Sulfide/metabolism , Imidazoles , Indoles , Liver/metabolism , Male , Oxidative Stress , Rats , SARS-CoV-2 , Vitamin E/pharmacology
13.
Drug Saf ; 44(11): 1125-1149, 2021 11.
Article in English | MEDLINE | ID: covidwho-1415119

ABSTRACT

Drug-induced liver injury (DILI) remains an important, yet challenging diagnosis for physicians. Each year, additional drugs are implicated in DILI and this year was no different, with more than 1400 articles published on the subject. This review examines some of the most significant highlights and controversies in DILI-related research over the past year and their implications for clinical practice. Several new drugs were approved by the US Food and Drug Administration including a number of drugs implicated in causing DILI, particularly among the chemotherapeutic classes. The COVID-19 pandemic was also a major focus of attention in 2020 and we discuss some of the notable aspects of COVID-19-related liver injury and its implications for diagnosing DILI. Updates in diagnostic and causality assessments related to DILI such as the Roussel Uclaf Causality Assessment Method are included, mindful that there is still no single biomarker or diagnostic tool to unequivocally diagnose DILI. Glutamate dehydrogenase received renewed attention as being more specific than alanine aminotransferase. There were a few new reports of previously unrecognized hepatotoxins, including immune modulators and novel gene therapy drugs that we highlight. Updates and new developments of previously described hepatotoxins, such as immune checkpoint inhibitors and anti-tuberculosis drugs are reviewed. Finally, novel technologies such as organoid culture systems to better predict DILI preclinically may be coming of age and determinants of hepatocyte loss, such as calculating PALT are poised to improve our current means of estimating DILI severity and the risk of acute liver failure.


Subject(s)
COVID-19/drug therapy , Chemical and Drug Induced Liver Injury , Causality , Humans , Risk Factors , SARS-CoV-2 , United States
16.
Clin Res Hepatol Gastroenterol ; 46(2): 101793, 2022 02.
Article in English | MEDLINE | ID: covidwho-1363934

ABSTRACT

Currently, there have been more than one hundred million confirmed cases of coronavirus disease 2019 (COVID-19), with two million deaths worldwide. This has caused a huge medical burden. Severe COVID-19 patients can experience multi-organ damage, including cardiac injury, kidney injury, and liver injury. About 2.0%-4.9% of COVID-19 cases involve patients with preexisting liver diseases. Additionally, preexisting liver diseases were reported and associated with severity (odds ratio (OR) or risk ratio (RR) = 1.48-1.70) and mortality (OR or RR = 1.08-2.65) among COVID-19 patients. Furthermore, the prevalence of liver injury was 16%-29% in COVID-19 patients. Higher prevalence of liver injury may worsen prognosis in patients (severity: OR or RR = 1.9-2.6; mortality: OR or RR = 1.1-4.0). The mechanisms of this association between liver injury and severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection are complex, including direct cholangiocyte damage induced by SARS-COV-2, cytokine storm, and drug-induced liver injury. In particular, drug-induced liver injury may be the most important reason. This review discusses the epidemiology of COVID-19 and liver dysfunction as well as potential mechanisms underlying the association between COVID-19 and liver dysfunction or other preexisting liver diseases. However, the association between preexisting liver diseases and COVID-19 prognosis and potential mechanisms underlying these associations require further prospective studies.


Subject(s)
COVID-19 , Liver Diseases , COVID-19/complications , COVID-19/drug therapy , COVID-19/epidemiology , Chemical and Drug Induced Liver Injury/epidemiology , Humans , Liver Diseases/epidemiology , Liver Diseases/virology , Risk Factors , SARS-CoV-2
17.
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
18.
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
19.
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
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