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

Area of Science:

• Hepatology
• Medical Diagnostics
• Clinical Risk Stratification

Background:

• Vibration-controlled transient elastography (VCTE) is used to predict liver-related events (LREs).
• The clinical significance of serial changes in liver stiffness (LS) measurements, particularly concerning magnitude, direction, and crossing established thresholds, remains unclear.
• The Baveno VII consensus proposed a 10 kPa threshold for significant liver stiffness.

Purpose of the Study:

• To evaluate a framework using threshold-defined liver stiffness (LS) trajectories to stratify LRE risk.
• To assess if this framework, anchored at the Baveno VII 10 kPa criterion, can predict LREs across diverse chronic liver disease etiologies.
• To identify patient subgroups with concentrated LRE risk based on LS changes over time.

Main Methods:

• Retrospective analysis of the V-LINK registry (2006-2020) including 6313 event-free patients with baseline and 1-year LS measurements.
• Patients were stratified into four LS trajectories: Stable Low, Improved, Worsened, and Persistent High, based on the 10 kPa threshold.
• Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs), with a 3-year landmark subset for reassessment.

Main Results:

• During a median 5.5-year follow-up, 472 LREs occurred. The 'Persistent High' LS trajectory group (14.4% of cohort) accounted for 61.9% of LREs.
• Compared to 'Stable Low', adjusted HRs for LREs were 1.5 for 'Improved', 2.5 for 'Worsened', and 4.1 for 'Persistent High'. 3-year risks were 1.2%, 3.2%, 3.8%, and 15.0% respectively.
• The risk gradient was preserved at 3 years, and the 'Persistent High' trajectory showed a significantly higher risk in non-viral (HR 6.4) versus viral (HR 2.6) etiologies.

Conclusions:

• Threshold-defined LS trajectories effectively identify a small subgroup of patients at high risk for LREs.
• Persistent elevation of LS above the 10 kPa threshold is a robust prognostic indicator for LREs.
• This approach highlights the importance of serial LS monitoring, especially in non-viral liver diseases, to guide clinical management.