Optimizing Biochemical Markers as Endpoints for Clinical Trials in Primary Biliary Cirrhosis

Abstract

Background Biochemical tests have been recommended as endpoints for clinical trials in primary biliary cirrhosis (PBC) because the use of liver transplantation and death as endpoints in ursodeoxycholic acid (UDCA) therapeutic trials is unfeasible. The best inclusion criteria cut-off values and cut-off for demonstrating treatment success have not been defined. Aim Our aim was to determine the optimal biochemical values for patient inclusion and to define values for treatment success in therapeutic trials. Methods We performed a retrospective review of 73 patients with PBC treated with UDCA followed over 36 months. Following one year of UDCA therapy, the likelihood of developing clinical endpoints of varices, ascites, encephalopathy, death or transplantation over the ensuing two years, based on degrees of elevation of biochemical markers, was analyzed using chi-square or Fisher's exact test. Results Patients with ALP≥2 X upper limit of normal (ULN) had a 2-fold greater likelihood of developing endpoints compared to patients with lower values (23% versus 11%), (p 1 mg/dL were 4 times more likely to develop endpoints compared to those with lower values (33% versus 8%), (p = 0.02). These values help identify the patient population for adjunctive therapy trials. Patients with ALP ≤1.67 X ULN and bilirubin ≤1mg/dL demonstrated the least likelihood of reaching adverse clinical endpoints and can be used to define treatment success. Conclusion Optimal ALP and Bilirubin levels can be used as appropriate biochemical criteria for patient selection and defining treatment success in future clinical trials in patients with PBC.