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

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 4,565 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 h 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. Conclusion: 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.