Glucose dysregulation is common in cirrhosis, yet its association with the progression from acute decompensation (AD) to acute-on-chronic liver failure (ACLF) remains undefined. We investigated the relationship between oral glucose tolerance test (OGTT)-derived 2-hour plasma glucose (2h-PG) levels and the risk of ACLF in patients with AD of hepatitis B virus (HBV)-related cirrhosis.

In this retrospective cohort study, 270 patients hospitalized for AD of HBV-related cirrhosis underwent a 75-g OGTT within 48 hours of admission. The primary outcome was progression to ACLF within 28 days. Restricted cubic spline (RCS) and multivariable Cox regression analyses were used to model the association between 2h-PG and ACLF risk and to identify an independent glycemic threshold.

Seventy-one patients (26.3%) progressed to ACLF within 28 days. Compared to those with normal glucose tolerance, patients with impaired glucose tolerance (IGT) [hazard ratio (HR) 3.057, 95% CI 1.370–6.817] and diabetes (HR 2.590, 95% CI 1.161–5.780) had a significantly higher risk of ACLF. RCS analysis revealed a significant nonlinear relationship between 2h-PG and ACLF risk, with an inflection point at 9.70 mmol/L. Patients with 2h-PG ≥ 9.70 mmol/L had a more than twofold increased risk of ACLF (adjusted HR 2.030, 95% CI 1.220–3.376). This association was consistent across all predefined clinical subgroups.

A 2h-PG level ≥ 9.70 mmol/L during early admission OGTT is an independent risk factor for progression to ACLF within 28 days in patients with AD of HBV-related cirrhosis. This threshold may aid in identifying high-risk patients for intensified monitoring.