Biochemical Response to Obeticholic Acid Drives Liver Stiffness Variation over Time and the Risk of Liver-Related Events in Patients with Primary Biliary Cholangitis

IntroductionIn PBC, the prognostic value of alkaline phosphatase, bilirubin and liver stiffness measurements(LSM) has been well established. However, the significance of their variation during treatment with obeticholic acid (OCA) has never been investigated.AimTo describe on-treatment trajectories of LSM based on biochemical response to OCA, and to evaluate associated risk of liver-related events (LRE) in a large cohort of OCA-treated PBC patients.Materials and MethodsWe used data from the Italian RECAPITULATE cohort, including OCA-treated PBC patients from centers belonging to the Italian PBC Registry and/or the CLEO/AIGO PBC study groups. Subjects with <6 months’ observation and cirrhotics in Child-Pugh B-C classes were excluded. Biochemical response was evaluated through POISE criteria. Linear mixed models were used to describe on-treatment variation of LSM, while Cox-models to assess the impact on LRE. Joint models were applied to estimate the association between LSM changes and LRE, defined as the occurrence of liver-related death, liver transplantation, or hepatic decompensation.Results631 PBC patients (median age 58, women 89%, cirrhosis 27%) accounted for 29 LRE during 19,164 patient-months (median follow-up, 30 months). A sub-cohort of 243 patients with at least two LSMs (total, 656 LSMs) was also analysed. POISE response rates were 42% and 58% at 1 and 3 years, respectively. LSM progressively increased in POISE non-responders (slope +0.44 KPa/year, 95%CI 0.04,0.85), while decreasing over time in responders (slope -0.45 KPa/year 95%CI -0.75,-0.13; p interaction<0.001). Patients attaining 1year-POISE response showed a significantly reduced incidence of LRE during follow-up (HR 0.22, 95%CI 0.08,0.59). Any increase in LSM was associated with an increased risk of LRE, with an overall HR per 10% increase in LSM/year of 1.39 (95%CI 1.18,1.67).ConclusionsIn patients with PBC, biochemical response to OCA translates into a reduction of LSM and of LRE during follow-up, while non-response is associated with increased LSM and risk of LRE.