Acute Liver Injury in COVID‐19: Prevalence and Association with Clinical Outcomes in a Large U.S. Cohort

Abstract

Background and Aims Coronavirus disease 2019 (COVID‐19) has been associated with acute liver injury (ALI) manifested by increased liver enzymes in reports worldwide. Prevalence of liver injury and associated clinical characteristics are not well defined. We aim to identify the prevalence of and risk factors for development of COVID‐19‐associated ALI in a large cohort in the United States. Approach and Results In this retrospective cohort study, all patients who underwent SARS‐CoV‐2 testing at three hospitals in the NewYork‐Presbyterian network were assessed. Of 3,381 patients, 2,273 tested positive and had higher initial and peak alanine aminotransferase (ALT) than those who tested negative. ALI was categorized as mild if ALT was greater than the upper limit of normal (ULN) but <2 times ULN, moderate if ALT was between 2 and 5 times the ULN, and severe if ALT was >5 times the ULN. Among patients who tested positive, 45% had mild, 21% moderate, and 6.4% severe liver injury (SLI). In multivariable analysis, severe ALI was significantly associated with elevated inflammatory markers, including ferritin (odds ratio [OR], 2.40; P < 0.001) and interleukin‐6 (OR, 1.45; P = 0.009). Patients with SLI had a more severe clinical course, including higher rates of intensive care unit admission (69%), intubation (65%), renal replacement therapy (RRT; 33%), and mortality (42%). In multivariable analysis, peak ALT was significantly associated with death or discharge to hospice (OR, 1.14; P = 0.044), controlling for age, body mass index, diabetes, hypertension, intubation, and RRT. Conclusions ALI is common in patients who test positive for SARS‐CoV‐2, but is most often mild. However, among the 6.4% of patients with SLI, a severe disease course should be anticipated.

Ferritin in the coronavirus disease 2019 (COVID‐19): A systematic review and meta‐analysis

“…Sun et al found that serum ferritin was high in severe and critically ill groups ( P < .001), and was positively associated with alanine aminotransferase (ALT) ( r = .385, P = .002), aspartate transaminase (AST) ( r = .437, P < .001), and LDH ( r = .394, P = .001) levels, but not with alkaline phosphatase (ALP) and gamma‐glutamyl transferase (GGT) 74 . Multivariable analysis in the study by Phipps et al also revealed that severe acute liver injury was significantly associated with high levels of ferritin (OR 2.40, P < .001) and these subsets of patients had a more severe clinical course 75 . Nevertheless, higher levels of ferritin were observed in COVID‐19 patients with increased aminotransferases according to Ramachandran et al study, although no statistical difference was observed ( P = .11) 76 …”

Letter: elevated liver enzymes and outcomes in COVID Authors' reply

“…2,5 Despite this, the elevation of liver chemistries seems to be associated with poor outcomes in COVID-19. 6,7 This is a strong association and is probably independent of the cause. 6 Elevated liver chemistries are a marker of disease severity.…”

Circulating Plasminogen Concentration at Admission in Patients with Coronavirus Disease 2019 (COVID-19)

“…Phipps et al reported in a large multicenter study that 6.4% of COVID-19 patients develop severe acute liver injury (alanine transaminase five times the upper limit of normal). 25 However, severe acute liver injury was not observed in any patient included in our cohort at the time of sample collection.…”