Abstract
BACKGROUND: Hepatitis E virus (HEV) infection is an important etiology of liver failure. This study aimed to explore the associations of blood fibrosis profiles with HEV-related liver failure (HEV-LF) onset and evaluate their prediction performance in hospitalized patients with acute hepatitis E. METHODS: Participants were obtained from two tertiary medical centers in Jiangsu, China, between January 2018 and November 2024. Cox proportional hazards regression, restricted cubic splines, and threshold effect analysis were used to examine associations between fibrosis markers and HEV-LF risk. The predictive value of these markers was evaluated for importance ranking, discrimination, calibration, and net benefit. RESULTS: Among 504 included participants, 59 developed HEV-LF during hospitalization. After adjusting for covariates, elevated baseline laminin (HR = 1.432, 95% CI: 1.080-1.900), fibrosis-4 score (HR = 1.865, 95% CI: 1.375-2.530), and aspartate aminotransferase to platelet ratio index (APRI) (HR = 1.603, 95% CI: 1.315-1.954) were associated with a higher HEV-LF risk in a dose-dependent manner. Hyaluronic acid (≤ 740 ng/mL: HR = 1.797, 95% CI: 1.177-2.744) and type IV collagen (≤ 137 ng/mL: HR = 3.075, 95% CI: 1.709-5.533) showed nonlinear associations. APRI was ranked the highest in importance, and its combination with the other two top important markers provided good discrimination (7-day HEV-LF: AUROC = 84.98%, 95% CI: 78.55-91.41; 14-day HEV-LF: AUROC = 80.11%, 95% CI: 73.49-86.73), calibration, and clinical utility for predicting HEV-LF onset. CONCLUSIONS: Several blood fibrosis markers are closely associated with HEV-LF risk and have promising predictive value. These findings may inform clinical risk stratification in patients with AHE. TRIAL REGISTRATION: Not applicable.