Prediction and evaluation of high-risk patients with primary biliary cholangitis receiving ursodeoxycholic acid therapy: an early criterion

Background and aims Current treatment guidelines recommend ursodeoxycholic acid (UDCA) as the first-line treatment for new-diagnosed primary biliary cholangitis (PBC) patients. However, up to 40% patients are insensitive to UDCA monotherapy, and evaluation of UDCA response at 12 months may result in long period of ineffective treatment. We aimed to develop a new criterion to reliably identify non-response patients much earlier. Methods Five hundred sixty-nine patients with an average of 59 months (Median: 53; IQR:32-79) follow-up periods were randomly divided into either the training (70%) or the validation cohort (30%). The efficiency of different combinations of total bilirubin (TBIL), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) threshold values to predict outcomes was assessed at 1, 3 or 6 month after the initiation of UDCA therapy. The endpoints were defined as adverse outcomes, including liver-related death, liver transplantation and complications of cirrhosis. Adverse outcome-free survival was compared using various published criteria and a proposed new criterion. Results A new criterion of evaluating UDCA responses at 1 month was established as: ALP <= 2.5 x upper limit of normal (ULN) and AST <= 2 x ULN, and TBIL <= 1 x ULN (Xi'an criterion). The 5 year adverse outcome-free survival rate of UDCA responders, defined by Xi'an criterion, was 97%, which was significantly higher than that of those non-responders (64%). An accurate distinguishing high-risk patients' capacity of Xi'an criterion was confirmed in both early and late-stage PBC. Conclusions Xi'an criterion has a similar or even higher ability to distinguish high-risk PBC patients than other published criteria. Xi'an criterion can facilitate early identification of patients requiring new therapeutic approaches.

Automated summary

This study aimed to develop a new criterion to identify primary biliary cholangitis (PBC) patients who do not respond to ursodeoxycholic acid (UDCA) treatment at an early stage. The Xi'an criterion, which evaluates UDCA response at 1 month, showed a high capacity to distinguish high-risk PBC patients.