Recent findings suggest that obese patients who present with non-alcoholic fatty liver of metabolic origin, also known as metabolic dysfunction-associated fatty liver disease (MAFLD) are at increased risk of getting infected with coronavirus disease 2019 (COVID-19) with severe symptoms. These patients have the higher likelihood of getting hospitalized and pharmacotherapy consisting of antiviral agents to manage acute respiratory distress syndrome and systemic inflammation, treat bacterial and fungal superinfections and reverse multi-organ failure. 

It has been observed that usually hospitalized COVID-19 patients are polymedicated, with the use of antiretrovirals such as lopinavir/ritonavir and remdesivir, antibiotics and antifungal agents. The use of these multiple drugs can significantly increase the risk of drug-drug interactions and can induce drug-induced liver injury (DILI). Researches also demonstrate that comorbidities such as obesity, MAFLD and diabetes may increase the risk of hepatotoxicity in Covid-19 patients. Although liver injury is not seen as the primary cause of mortality in COVID-19 patients, hepatic dysfunction can worsen the condition of the patient, by reducing the synthesis of coagulation proteins including factors II, V, VII, X, and fibrinogen. 

The authors of the present study hypothesized that obese COVID-19 patients with MAFLD can be at higher risk for DILI in contrast to non-infected healthy individuals or MAFLD patients. The high risk of DILI is attributed to several concomitant factors, such as polypharmacy, systemic inflammation at risk of cytokine storm, fatty liver and sometimes nonalcoholic steatohepatitis (NASH) as well as insulin resistance and other diseases associated with obesity. The underlying mechanism of the hepatoxicity is not yet understood, however, mainly include impaired activity of xenobiotic-metabolizing enzymes, mitochondrial dysfunction, altered lipid homeostasis and oxidative stress.

Thus, it can be postulated that certain drugs can cause more severe or more common DILI in obese COVID-19 patients, whereas in others, it can stimulate the progression of fatty liver to NASH, or aggravates pre-existing steatosis, necroinflammation and fibrosis. Thus, it is essential to recognize drugs that are implicated for increased risk of liver injury in Covid-19 patients, particularly in those with obesity and related metabolic diseases.  

Source: Ferron PJ, Gicquel T, Mégarbane B, Clément B, Fromenty B. Treatments in Covid-19 patients with pre-existing metabolic dysfunction-associated fatty liver disease: A potential threat for drug-induced liver injury? Biochimie. 2020;179:266-274.