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Treatments in Covid-19 patients with pre-existing metabolic dysfunction-associated fatty liver disease: A potential threat for drug-induced liver injury?
Ferron, PJ, Gicquel, T, Mégarbane, B, Clément, B, Fromenty, B
Biochimie. 2020;:266-274
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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.
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Nutrition Therapy in Critically Ill Patients With Coronavirus Disease 2019.
Martindale, R, Patel, JJ, Taylor, B, Arabi, YM, Warren, M, McClave, SA
JPEN. Journal of parenteral and enteral nutrition. 2020;(7):1174-1184
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Abstract
In the midst of a coronavirus disease 2019 (COVID-19) pandemic, a paucity of data precludes derivation of COVID-19-specific recommendations for nutrition therapy. Until more data are available, focus must be centered on principles of critical care nutrition modified for the constraints of this disease process, ie, COVID-19-relevant recommendations. Delivery of nutrition therapy must include strategies to reduce exposure and spread of disease by providing clustered care, adequate protection of healthcare providers, and preservation of personal protective equipment. Enteral nutrition (EN) should be initiated early after admission to the intensive care unit (ICU) using a standard isosmolar polymeric formula, starting at trophic doses and advancing as tolerated, while monitoring for gastrointestinal intolerance, hemodynamic instability, and metabolic derangements. Intragastric EN may be provided safely, even with use of prone-positioning and extracorporeal membrane oxygenation. Clinicians should have a lower threshold for switching to parenteral nutrition in cases of intolerance, high risk of aspiration, or escalating vasopressor support. Although data extrapolated from experience in acute respiratory distress syndrome warrants use of fiber additives and probiotic organisms, the lack of benefit precludes a recommendation for micronutrient supplementation. Practices that increase exposure or contamination of equipment, such as monitoring gastric residual volumes, indirect calorimetry to calculate requirements, endoscopy or fluoroscopy to achieve enteral access, or transport out of the ICU for additional imaging, should be avoided. At all times, strategies for nutrition therapy need to be assessed on a risk/benefit basis, paying attention to risk for both the patient and the healthcare provider.