Abstract

Introduction: COVID-19, in addition to its direct detrimental respiratory infection, is associated with multiple systemic complications involving different organs, including the liver. COVID-19 has been associated with liver injury through multiple mechanisms, including direct viral effects on liver cells, immune-mediated injury, cytokine-driven inflammation, ischemic hepatitis, microvascular thrombosis, and sepsis-related multiorgan dysfunction. Acute liver failure (ALF) is the acute form of liver damage, which has a high mortality, and recovery is dependent on various factors. We studied the effect of COVID-19 on clinical outcomes such as mortality, length of stay, and need for non-invasive and invasive ventilation in patients with acute liver failure. Methods: We performed a retrospective cohort analysis using the Nationwide Inpatient Sample (NIS) database from 2020 to 2022. Adult patients admitted to the hospital with acute liver failure were divided into 2 groups based on their COVID-19 infection status. We analyzed differences in mortality, length of stay, need for non-invasive and invasive ventilation, acute kidney injury, need for renal replacement therapy, and total charges to evaluate the effects on outcomes, and the results were then adjusted for demographic and hospital factors. Results: Of 633,155 patients with acute liver failure, 66,785 had concurrent COVID-19 infection, while 566,370 did not. Patients with concurrent COVID-19 infection had significantly higher in-hospital mortality (63.9% vs. 36.0%) and greater utilization of noninvasive ventilation (14.9% vs. 6.4%), invasive mechanical ventilation (68.9% vs. 41.7%), higher incidence of acute kidney injury (81.4% vs. 70.3%) and higher need for renal replacement therapy (26.8% vs. 16.9%). They also experienced longer hospital stays (17.1 vs. 10.7 days) and higher total charges ($345,072 vs. $221,268). The findings were statistically significant after adjusting for demographics and clinical factors. Conclusions: Patients hospitalized with acute liver failure and concurrent COVID-19 infection experienced worse clinical outcomes, including higher in-hospital mortality, greater need for ventilatory support and renal replacement therapy, and higher hospital resource utilization. Notably, COVID-19 was independently associated with worse outcomes even among patients with fewer baseline comorbidities. These findings underscore the importance of early recognition of COVID-19 in patients presenting with acute liver failure, as well as prompt, multidisciplinary management to optimize clinical outcomes.

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