Dynamics of liver stiffness measurement and clinical course of primary biliary cholangitis

Background & aims: In primary biliary cholangitis (PBC), static liver stiffness measurement (LSM) has proven prognostic value. However, the added prognostic value of LSM time course in this disease remains uncertain. Methods: We conducted an international retrospective cohort study among PBC patients treated with ursodeoxycholic acid (UDCA) and followed by vibration-controlled transient elastography (VCTE) between 2003 and 2022. Using joint modeling, the association of LSM trajectory and the incidence of serious clinical events (SCE), defined as cirrhosis complications, liver transplantation (LT) or death, was quantified using the hazard ratio (HR) and its confidence interval (CI). Results: A total of 6,362 LSMs were performed in 3,078 patients (2,007 on UDCA alone; 13% with cirrhosis), in whom 316 SCE occurred over 14,445 person-years (median follow-up, 4.2 years; incidence rate, 21.9 per 1,000 person-years). LSM progressed in 59% of patients (mean 0.39 kPa/year). After adjusting for prognostic factors at baseline, including LSM, any relative change in LSM was associated with a significant variation in SCE risk (p<0.001). For example, the adjusted HRs (95% CI) associated with a 20% annual variation in LSM were 2.13 (1.89 - 2.45) for the increase and 0.40 (0.33 - 0.46) for the decrease. The association between LSM trajectory and SCE risk persisted regardless of treatment response or duration, when patients with cirrhosis were excluded, and when only death or LT was considered. Conclusions: Tracking longitudinal changes in LSM using VCTE provides valuable insights into PBC prognosis, offering a robust predictive measure for the risk of SCE. LSM could be used as a clinically relevant surrogate endpoint in PBC clinical trials.