Research Article Details
| Article ID: | A06405 |
| PMID: | 32891697 |
| Source: | Biochimie |
| Title: | Treatments in Covid-19 patients with pre-existing metabolic dysfunction-associated fatty liver disease: A potential threat for drug-induced liver injury? |
| Abstract: | Obese patients who often present metabolic dysfunction-associated fatty liver disease (MAFLD) are at risk of severe presentation of coronavirus disease 2019 (COVID-19). These patients are more likely to be hospitalized and receive antiviral agents and other drugs required to treat acute respiratory distress syndrome and systemic inflammation, combat bacterial and fungal superinfections and reverse multi-organ failure. Among these pharmaceuticals, antiretrovirals such as lopinavir/ritonavir and remdesivir, antibiotics and antifungal agents can induce drug-induced liver injury (DILI), whose mechanisms are not always understood. In the present article, we hypothesize that obese COVID-19 patients with MAFLD might be at higher risk for DILI than non-infected healthy individuals or MAFLD patients. These patients present several concomitant factors, which individually can favour DILI: polypharmacy, systemic inflammation at risk of cytokine storm, fatty liver and sometimes nonalcoholic steatohepatitis (NASH) as well as insulin resistance and other diseases linked to obesity. Hence, in obese COVID-19 patients, some drugs might cause more severe (and/or more frequent) DILI, while others might trigger the transition of fatty liver to NASH, or worsen pre-existing steatosis, necroinflammation and fibrosis. We also present the main mechanisms whereby drugs can be more hepatotoxic in MAFLD including impaired activity of xenobiotic-metabolizing enzymes, mitochondrial dysfunction, altered lipid homeostasis and oxidative stress. Although comprehensive investigations are needed to confirm our hypothesis, we believe that the current epidemic of obesity and related metabolic diseases has extensively contributed to increase the number of cases of DILI in COVID-19 patients, which may have participated in presentation severity and death. |
| DOI: | 10.1016/j.biochi.2020.08.018 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I01 | 552 | Pneumonia | A lung disease that involves lung parenchyma or alveolar inflammation and abnormal alveolar filling with fluid (consolidation and exudation). It results from a variety of causes including infection with bacteria, viruses, fungi or parasites, and chemical or physical injury to the lungs. It is accompanied by fever, chills, cough, and difficulty in breathing. http://en.wikipedia.org/wiki/Pneumonia | disease of anatomical entity/respiratory system disease/ lower respiratory tract disease/lung disease | Details |
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |