Serum GPC3 and AKR1B10 as Diagnostic Biomarkers for Hepatitis E Virus-Associated Acute Liver Failure

Hepatitis E virus (HEV)-associated acute liver failure (ALF) lacks reliable biomarkers for risk stratification at hospital admission. This study evaluated the diagnostic utility of serum glypican-3 (GPC3) and aldo-keto reductase family 1 member B10 (AKR1B10).

Between May 2023 and May 2025, 231 adults with acute HEV infection were classified as HEV-ALF (n = 43) or HEV without ALF (n = 188). Serum GPC3 and AKR1B10 concentrations were measured using enzyme linked immunosorbent assay. Associations were evaluated using Pearson correlation coefficient r; diagnostic performance was assessed by receiver operating characteristic curves, and independent predictors of ALF were identified using multivariable logistic regression.

Patients with HEV-ALF had lower albumin, triglyceride, and cholesterol levels and higher total bilirubin, prothrombin time, and international normalized ratio values than patients without ALF (all P < .05). GPC3 and AKR1B10 concentrations were markedly elevated in the HEV-ALF group (both P < .001) and were strongly correlated (r = 0.610, P < .001). The combination of GPC3 and AKR1B10 demonstrated superior diagnostic performance for identifying ALF, with an area under the curve (AUC) of 0.931, outperforming either GPC3 alone (AUC, 0.832) or AKR1B10 alone (AUC, 0.792). In multivariable logistic regression analysis, elevated GPC3 (odds ratio [OR], 2.138; 95% CI, 1.213-3.771) and AKR1B10 (OR, 2.304; 95% CI, 1.215-4.368) remained independent risk factors for ALF.

Serum GPC3 and AKR1B10 were independent predictors of HEV-ALF and may facilitate risk stratification at hospital admission.