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 Treatment , 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 FactorsABSTRACT
BACKGROUND: Metabolic diseases are risk factors for severe Coronavirus disease (COVID-19), which have a close relationship with metabolic dysfunction-associated fatty liver disease (MAFLD). AIMS: To evaluate the presence of MAFLD and fibrosis in patients with COVID-19 and its association with prognosis. METHODS: Retrospective cohort study. In hospitalized patients with COVID-19, the presence of liver steatosis was determined by computed tomography scan (CT). Liver fibrosis was assessed using the NAFLD fibrosis score (NFS score), and when altered, the AST to platelet ratio index (APRI) score. Mann-Whitney U, Student´s t-test, logistic regression analysis, Kaplan-Meier curves and Cox regression analysis were used. RESULTS: 432 patients were analyzed, finding steatosis in 40.6%. No differences in pulmonary involvement on CT scan, treatment, or number of days between the onset of symptoms and hospital admission were found between patients with and without MAFLD. The presence of liver fibrosis was associated with higher severity scores, higher levels of inflammatory markers, requirement of mechanical ventilation, incidence of acute kidney injury (AKI), and higher mortality than patients without fibrosis. CONCLUSION: The presence of fibrosis rather than the presence of MAFLD is associated with increased risk for mechanical ventilation, development of AKI, and higher mortality in COVID-19 patients.
Subject(s)
COVID-19 , Fatty Liver , Liver Cirrhosis , Liver , Respiration, Artificial/statistics & numerical data , Aspartate Aminotransferases/blood , Biomarkers/blood , Blood Platelets/pathology , COVID-19/blood , COVID-19/complications , COVID-19/mortality , COVID-19/therapy , Fatty Liver/diagnosis , Fatty Liver/epidemiology , Fatty Liver/metabolism , Female , Humans , Liver/diagnostic imaging , Liver/metabolism , Liver/pathology , Liver Cirrhosis/diagnosis , Liver Cirrhosis/epidemiology , Liver Cirrhosis/metabolism , Liver Function Tests/methods , Male , Mexico/epidemiology , Middle Aged , Prognosis , Research Design , Retrospective Studies , Risk Factors , Severity of Illness Index , Tomography, X-Ray Computed/methodsABSTRACT
BACKGROUND: The association between metabolic-associated fatty liver disease (MAFLD) and disease progression in patients with the coronavirus disease 2019 (COVID-19) are unclear. AIMS: To explore the association between MAFLD and the severity of COVID-19 by meta-analysis. METHODS: We conducted a literature search using PubMed, EMBASE, Medline (OVID), and MedRxiv from inception to July 6, 2020. Newcastle-Ottawa Scale (NOS) and Stata 14.0 were used for quality assessment of included studies as well as for performing a pooled analysis. RESULTS: A total of 6 studies with 1,293 participants were included after screening. Four studies reported the prevalence of MAFLD patients with COVID-19, with a pooled prevalence of 0.31 for MAFLD (95CI 0.28, 0.35, I2â¯=â¯38.8%, Pâ¯=â¯0.179). MAFLD increased the risk of COVID-19 disease severity, with a pooled OR of 2.93 (95CI 1.87, 4.60, I2â¯=â¯34.3%, Pâ¯=â¯0.166). CONCLUSION: In this meta-analysis, we found that a high percentage of patients with COVID-19 had MAFLD. Meanwhile, MAFLD increased the risk of disease progression among patients with COVID-19. Thus, better intensive care and monitoring are needed for MAFLD patients infected by SARS-COV-2.