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

ABSTRACT Background & Aims 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. Methods 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). Results 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). Conclusions 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.