Risk stratification for patients with primary biliary cholangitis: early versus advanced-stage or non-cirrhosis versus cirrhosis?

Background: Primary biliary cholangitis (PBC) is divided into early and advanced stages, which are two distinct disease states, and whether this division is optimal remains to be demonstrated.

Aims: A risk stratification strategy was re-established according to histological stages and response criteria were defined accordingly.

Methods: We retrospectively analyzed 721 patients with histological data. The endpoint events were liver-related death and liver transplantation (LT).

Results: Histological stage IV was associated with LT-free survival compared to stage III (HR: 2.764, 95% CI: 1.457-5.247, p = 0.002); and stage III was not associated with LT-free survival compared to stage II (HR: 1.632, 95% CI: 0.833-3.195, p = 0.153). Total bilirubin was associated with LT-free survival (HR: 1.162, 95% CI: 1.079-1.251, p < 0.001), whereas alkaline phosphatase was not associated with LT-free survival in cirrhotic patients (HR: 1.256, 95% CI: 0.958-1.648, p = 0.100). Compared to Paris I, Paris II, and Toronto, Rotterdam had the highest area under the receiver operating characteristic curve (AUC) for predicting the 5-year endpoint events in cirrhotic patients (0.652 [0.558-0.745]). Patients who had poor response according to Rotterdam criteria had worse prognosis than those who were biochemical responders (p = 0.036). Compared to Paris II and Paris I (for stage III) + Paris II (for stage I-II), Paris I, Rotterdam, and Toronto had higher AUC in non-cirrhotic patients (p < 0.05).

Conclusions: Risk stratification based on histological classification of non-cirrhosis versus cirrhosis demonstrates superior clinical utility compared to the early versus advanced stage stratification. Furthermore, the Rotterdam criteria proved to be clinically applicable for assessing biochemical responses specifically in patients with histological cirrhosis.