Elevated non-invasive liver fibrosis scores at admission are independent risk factors for severe COVID-19: a retrospective cohort study from 2020-2024

Nicole E Naiman^1*Lucia Cabrejos Hirashima¹Amyn A. Malik¹Mamta K. Jain^1,2

• ¹University of Texas Southwestern Medical Center, Dallas, United States
• ²Parkland Health, Dallas, United States

Background: COVID-19 patients frequently present with abnormal liver function tests (LFTs) and elevated non-invasive liver fibrosis scores, such as the fibrosis 4 index (FIB-4), the non-alcoholic fatty liver disease fibrosis score (NFS), and the aspartate aminotransferase (AST)-to-platelet ratio index (APRI). While elevated LFTs and non-invasive liver fibrosis scores in COVID-19 patients have been associated with poor COVID-19 outcome, most of those data were collected before the dominance of the Omicron variant and shift in disease presentation to a milder respiratory presentation. Methods: This was a retrospective cohort study of 4565 non-pregnant adults admitted with COVID-19 from 03/01/2020 to 12/31/2024. We examined the association of LFT and non-invasive liver fibrosis score derangements near admission with relative risk of severe COVID-19, a composite outcome defined as death and/or requirement of organ support. Subgroup analyses included: a “non-liver disease subgroup” (patients without known prior liver disease, viral hepatitis, or prior remdesivir use), a “room air subgroup” (patients who remained on room air during the first 24 hours of admission), and viral variant subgroups defined by date. Multivariable regression models were compared via area under the receiver operating characteristic (ROC) curve and Akaike Information Criterion (AIC). Results: Elevations in FIB-4, NFS, and APRI were associated with increased risk of severe COVID-19 in the total cohort and across various subgroups. High FIB-4 (>2.67) and intermediate APRI (0.5-1.0) were associated with increased risk of severe COVID-19 in the total cohort (FIB-4 RR: 2.25, 95% CI 1.81-2.79; APRI RR: 1.53, 95% CI 1.32-1.79), with similar results in the non-liver disease subgroup and across the Pre-Delta, Delta, and Omicron subgroups. High NFS (>0.675) was associated with increased risk of severe COVID-19 in the total cohort (RR: 2.33, 95% CI 1.83-2.97), with similar results in the room air, Pre-Delta, and Delta subgroups. Overall, the models had similar outcome discrimination based on area under the ROCs, but the FIB-4 models had the best fit based on AICs. Conclusions: Elevated non-invasive liver fibrosis scores at admission were associated with risk of severe COVID-19 across variants regardless of the baseline respiratory status or liver health of COVID-19 patients in this cohort.