Threshold-Defined Liver Stiffness Trajectories and Liver-Related Event Risk in Chronic Liver Disease: A Cohort Study

Vibration-controlled transient elastography (VCTE) predicts liver-related events (LREs), but how serial liver stiffness (LS) changes should be translated into clinical risk-whether by their magnitude, direction or movement across established thresholds-remains uncertain. We tested whether a threshold-defined trajectory framework anchored at the Baveno VII 10 kPa criterion would stratify LRE risk across chronic liver disease aetiologies.

From the retrospective V-LINK registry (2006-2020), 6313 event-free patients with baseline and 1-year LS were stratified by the 10 kPa threshold into Stable Low, Improved, Worsened or Persistent High trajectories. A 3-year landmark (LM3) subset (n = 1617) enabled trajectory reassessment over time. Cox models estimated adjusted hazard ratios (HRs).

During a median follow-up of 5.5 years, 472 LREs occurred. Compared with Stable Low, adjusted HRs were 1.5 (95% confidence interval [CI], 1.1-2.2) for Improved, 2.5 (1.5-4.3) for Worsened and 4.1 (3.1-5.5) for Persistent High, with 3-year risks of 1.2%, 3.2%, 3.8%, and 15.0%. Persistent High (14.4% of the cohort) accounted for 61.9% of LREs; 65.7% showed a numerical decrease in LS yet remained ≥ 10 kPa. By aetiology, the HR for Persistent High was 6.4 (4.0-10.2) in non-viral aetiologies versus 2.6 (1.8-3.8) in viral aetiologies (p for interaction < 0.001). At LM3, the trajectory-based risk gradient was preserved (Persistent High HR, 3.5; 95% CI, 2.2-5.5).

Threshold-defined LS trajectories identified a small subgroup concentrating most LRE risk, with the largest gradient in non-viral aetiologies. Persistent threshold elevation was the most robust prognostic signal, supporting serial LS monitoring pending external validation.