Serum extracellular vesicle-derived ASS1 is a promising predictor for the occurrence of HEV-ALF.

Development of biomarkers for predicting the occurrence of hepatitis E virus related-acute liver failure (HEV-ALF) is conducive to prevention and early intervention. Serum samples from 250 HEV-ALF patients, 250 patients with acute hepatitis E (AHE) and 250 health controls (HCs) were collected. We assessed the predictive ability of extracellular vesicle (EV)-derived argininosuccinate synthase 1 (ASS1) levels for HEV-ALF occurrence. Serum EVs were successfully isolated. EV-derived ASS1 levels in the HEV-ALF patients were significantly higher than those in the AHE patients and HCs. In HEV-ALF patients, EV-derived ASS1 levels were positively correlated with the number of failed organs and disease progression. The logistical regression showed that EV-derived ASS1 level is an independent risk factor for HEV-ALF, and orthogonal partial least squares discriminant analysis (OPLS-DA) also suggested that EV-derived ASS1 level has high predictive capability. Besides, the area under the curve (AUC) of EV-derived ASS1 level to predict HEV-ALF occurrence was 0.728 (0.684-0.772) with the sensitivity and specificity being 72.80% and 64.80%, which had a high decision-making ability. Furthermore, there existed no significant difference between the age ≥60 and age <60 groups in EV-derived ASS1 levels. Serum EV-derived ASS1 level is a promising predictor for the occurrence of HEV-ALF.