Drug-induced liver injury and COVID-19: A review for clinical practice

Ortiz, Gabriela Xavier; Lenhart, Gabriele; Becker, Matheus William; Schwambach, Karin Hepp; Tovo, Cristiane Valle; Blatt, Carine Raquel

doi:10.4254/wjh.v13.i9.1143

Cited by 20 publications

(13 citation statements)

References 45 publications

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“…In addition, drugs of pharmacologic treatments against SARS-CoV-2 (DPTS) are repurposed and off-label used in combination due to the lack of standard guideline for COVID-19 management ( Ortiz et al, 2021 ). Pharmacotherapy against SARS-CoV-2 not only inhibits virus replication, but also mediates immune-induced inflammation in COVID-19 patients suffering this specific disease state (both virus infection and CRS) ( Yongzhi, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, certain drugs including lopinavir/ritonavir and tocilizumab were responsible for DILI in COVID-19 patients ( Boeckmans et al, 2020 ; Olry et al, 2020 ; Zhang et al, 2020 ). Currently, liver injury induced by DPTS, related with the different PK behaviors of DPTS from those provided by drug labels and the possible adverse drug combinations, are getting concern in the management of COVID-19 ( Ali, 2020 ; Ali and Hossain, 2020 ; Ortiz et al, 2021 ; Zhang et al, 2022 ). However, the exact mechanism underlying DILI in COVID-19 patients were not yet fully understood and no systematic analysis exists.…”

Section: Introductionmentioning

confidence: 99%

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Identifying Drug-Induced Liver Injury Associated With Inflammation-Drug and Drug-Drug Interactions in Pharmacologic Treatments for COVID-19 by Bioinformatics and System Biology Analyses: The Role of Pregnane X Receptor

et al. 2022

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Of the patients infected with coronavirus disease 2019 (COVID-19), approximately 14–53% developed liver injury resulting in poor outcomes. Drug-induced liver injury (DILI) is the primary cause of liver injury in COVID-19 patients. In this study, we elucidated liver injury mechanism induced by drugs of pharmacologic treatments against SARS-CoV-2 (DPTS) using bioinformatics and systems biology. Totally, 1209 genes directly related to 216 DPTS (DPTSGs) were genes encoding pharmacokinetics and therapeutic targets of DPTS and enriched in the pathways related to drug metabolism of CYP450s, pregnane X receptor (PXR), and COVID-19 adverse outcome. A network, constructed by 110 candidate targets which were the shared part of DPTSGs and 445 DILI targets, identified 49 key targets and four Molecular Complex Detection clusters. Enrichment results revealed that the 4 clusters were related to inflammatory responses, CYP450s regulated by PXR, NRF2-regualted oxidative stress, and HLA-related adaptive immunity respectively. In cluster 1, IL6, IL1B, TNF, and CCL2 of the top ten key targets were enriched in COVID-19 adverse outcomes pathway, indicating the exacerbation of COVID-19 inflammation on DILI. PXR-CYP3A4 expression of cluster 2 caused DILI through inflammation-drug interaction and drug-drug interactions among pharmaco-immunomodulatory agents, including tocilizumab, glucocorticoids (dexamethasone, methylprednisolone, and hydrocortisone), and ritonavir. NRF2 of cluster 3 and HLA targets of cluster four promoted DILI, being related to ritonavir/glucocorticoids and clavulanate/vancomycin. This study showed the pivotal role of PXR associated with inflammation-drug and drug-drug interactions on DILI and highlighted the cautious clinical decision-making for pharmacotherapy to avoid DILI in the treatment of COVID-19 patients.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identifying Drug-Induced Liver Injury Associated With Inflammation-Drug and Drug-Drug Interactions in Pharmacologic Treatments for COVID-19 by Bioinformatics and System Biology Analyses: The Role of Pregnane X Receptor

et al. 2022

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“…While the disease continues to be transmitted by the latest variants, COVID-19 infections has been treated symptomatically without specific drugs until today. A recent study, which investigated the drug safety in COVID-19 patients who received Remdesivir for their treatment, suggested that the antiviral drug might cause hepatocellular injury [ 22 ]. Another randomized, double-blinded, placebo-controlled, and multicenter trial conducted in a large Chinese population for the treatment of COVID-19 has shown that the association between the Remdesivir treatment and its clinical benefits was not statistically significant [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Plant-Derived Antiviral Compounds as Potential Entry Inhibitors against Spike Protein of SARS-CoV-2 Wild-Type and Delta Variant: An Integrative in SilicoApproach

Surapaneni¹,

Kullappan²,

Patil

et al. 2022

Molecules

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The wild-type SARS-CoV-2 has continuously evolved into several variants with increased transmissibility and virulence. The Delta variant which was initially identified in India created a devastating impact throughout the country during the second wave. While the efficacy of the existing vaccines against the latest SARS-CoV-2 variants remains unclear, extensive research is being carried out to develop potential antiviral drugs through approaches like in silico screening and drug-repurposing. This study aimed to conduct the docking-based virtual screening of 50 potential phytochemical compounds against a Spike glycoprotein of the wild-type and the Delta SARS-CoV-2 variant. Subsequently, molecular docking was performed for the five best compounds, such as Lupeol, Betulin, Hypericin, Corilagin, and Geraniin, along with synthetic controls. From the results obtained, it was evident that Lupeol exhibited a remarkable binding affinity towards the wild-type Spike protein (−8.54 kcal/mol), while Betulin showed significant binding interactions with the mutated Spike protein (−8.83 kcal/mol), respectively. The binding energy values of the selected plant compounds were slightly higher than that of the controls. Key hydrogen bonding and hydrophobic interactions of the resulting complexes were visualized, which explained their greater binding affinity against the target proteins—the Delta S protein of SARS-CoV-2, in particular. The lower RMSD, the RMSF values of the complexes and the ligands, Rg, H-bonds, and the binding free energies of the complexes together revealed the stability of the complexes and significant binding affinities of the ligands towards the target proteins. Our study suggests that Lupeol and Betulin could be considered as potential ligands for SARS-CoV-2 spike antagonists. Further experimental validations might provide new insights for the possible antiviral therapeutic interventions of the identified lead compounds and their analogs against COVID-19 infection.

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“…A májkárosodás jelenlétét önmagában laboratóriumi paraméterek is jelezhetik a következő kritériumok alapján: 1) a szérumglutamát-piruvát-transzamináz (GPT) aktivitása ≥5× a labor-referenciatartomány felső határa (ULN) feletti, 2) a szérum-GPT ≥3×, míg a szérumbilirubin ≥2× az ULN feletti, és/vagy az alkalikus foszfatáz (ALP) aktivitásának emelkedése vagy klinikai tünetek megjelenése, 3) a szérumbilirubin >43 µmol/l, és a szérum GOT/GPT arány is emelkedett, 4) INR>1,5, és a szérum GOT/GPT arány is emelkedett. A szérumtranszamináz-aktivitás emelkedése mellett ritkábban előforduló változás a GGT-és az ALP-aktivitás emelkedése is, valamint a szérum albuminszintjének csökkenése [8]. A GPT és a di-…”

Section: A Szérummájenzim-aktivitás Emelkedése Covid-19-fertőzés Soránunclassified

“…A gyógyszer okozta májkárosodás a klinikai gyakorlatban általában kizárásos diagnózis. Abban az esetben gondolhatunk rá, ha a beteg klinikuma javul, a májpanel (GOT, GPT, GGT, ALP, szérumbilirubin) értékeinek romlása mellett [8]. A COVID-19-ben szenvedő betegek esetében a kóros májenzim-emelkedés a remdesivir-, a tocilizumab-, a baricitinib-, a favipiravir-és a szisztémás kortikoszteroid-kezelés mellett is előfordulhat ismert mellékhatásként [6].…”

Section: Gyógyszer Okozta Májkárosodásunclassified

A COVID–19-hez kapcsolódó májenzim-emelkedés valószínűleg multifaktoriális eredetű

Gáspár

Szabó

Kiss-Dala

et al. 2022

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A COVID–19 kapcsán tapasztalható jelenség a szérummájenzim-aktivitásnak a laboratóriumi vizsgálat során észlelt emelkedése. Ezen változások hátterében feltehetően három patomechanizmus áll: 1) a SARS-CoV-2 direkt citotoxikus és indirekt sejtszintű és szisztémás következményei, 2) a COVID–19-ben alkalmazott gyógyszeres kezeléseknek (remdesivir, favipiravir, tocilizumab, baricitinib, szisztémás kortikoszteroid) a farmakológiai hatásai, illetve 3) a betegekben korábban fennálló krónikus májbetegség(ek) progressziója. A májenzim-emelkedés kiváltó okának differenciáldiagnosztikája és a terápiával kapcsolatos döntéshozatal kihívást jelenthet a klinikus számára, mivel a nem megfelelő kezelés a COVID–19 vagy a májkárosodás progresszióját okozhatja. A jelen összefoglaló a COVID–19-betegeket ellátó klinikusok számára kíván alapvető támpontot nyújtani a helyes döntéshez. Orv Hetil. 2022; 163(36): 1415–1421.

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Drug-induced liver injury and COVID-19: A review for clinical practice

Cited by 20 publications

References 45 publications

Identifying Drug-Induced Liver Injury Associated With Inflammation-Drug and Drug-Drug Interactions in Pharmacologic Treatments for COVID-19 by Bioinformatics and System Biology Analyses: The Role of Pregnane X Receptor

Identifying Drug-Induced Liver Injury Associated With Inflammation-Drug and Drug-Drug Interactions in Pharmacologic Treatments for COVID-19 by Bioinformatics and System Biology Analyses: The Role of Pregnane X Receptor

Plant-Derived Antiviral Compounds as Potential Entry Inhibitors against Spike Protein of SARS-CoV-2 Wild-Type and Delta Variant: An Integrative in SilicoApproach

A COVID–19-hez kapcsolódó májenzim-emelkedés valószínűleg multifaktoriális eredetű

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