Prognostic value of liver stiffness measurement vs. biochemical response in primary biliary cholangitis

Abstract

Background & aims: Both liver stiffness measurement (LSM) and biochemical response have prognostic significance in patients with primary biliary cholangitis (PBC). However, the frequency and clinical relevance of discordant biochemical and LSM changes remain unclear. We aim to determine the performance of the most recent or current LSM (LSMc) in predicting first hepatic decompensation (HD) in the setting of discordant biochemical and LSM responses.

Methods: In this international, multicenter study, we included patients with at least two reliable LSM performed at least 6 months apart. Patients with prior HD, liver transplantation or hepatocellular carcinoma were excluded. Biochemical response was based on the Paris-II criteria. LSM response was defined as stable or any reduction in LSM. The primary outcome was the occurrence of the first HD. Secondary outcomes were liver transplantation and liver-related death. The influence of LSM on HD was estimated using Cox regression analysis.

Results: A total of 1,793 patients with PBC were analyzed. Over a median follow-up of 22 (IQR 12-39) months, 3.3% developed HD. Up to 55% of patients with PBC exhibited discordance between LSM and biochemical response. Among patients with LSM response, achieving Paris-II criteria was associated with a lower risk of HD (hazard ratio [HR] 0.25, 95% CI 0.06-0.97, p <0.044). Among patients with biochemical response, LSM response did not influence the risk of developing HD (HR 0.64, 95% CI 0.21-1.96, p = 0.429). The LSMc >10 kPa strongly predicted HD (HR 14.5, 95% CI 6.9-30.6, p <0.001), irrespective of biochemical response and prior LSM trajectories.

Conclusions: Discordance between LSM and biochemical response is frequent. Most recent or current LSM is the strongest predictor of first liver-related events in patients with PBC, irrespective of prior biochemical response or LSM trajectory.

Impact and implications: Both liver stiffness measurement (LSM) and biochemical response have prognostic significance in patients with primary biliary cholangitis. However, the clinical relevance and how discordant biochemical and LSM changes should be best interpreted remain unclear. In this large international multicenter study, we demonstrated that once the current LSM is known, prior LSM trajectories and biochemical changes did not improve the prediction of liver-related events in patients with primary biliary cholangitis. Our finding addresses a common clinical dilemma in risk-stratifying PBC patients with discordant biochemical and LSM responses. Importantly, the use of the latest LSM value for risk prediction significantly simplifies the use of LSM in clinical decision-making for PBC patients with multiple LSM readings.

Keywords: Liver stiffness; clinically significant portal hypertension; decompensation; non-invasive; portal hypertension; prediction; vibration-controlled elastography.