Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis

TLDR

Biochemical response to UDCA in primary biliary cirrhosis is variable, and an ALP decline >40 % or normalization after one year (Barcelona criteria) has been proposed as a marker of long‑term prognosis, while patients lacking this response or with advanced histology warrant further research. The study aimed to identify the most efficient biochemical markers that predict death or liver transplantation in UDCA‑treated PBC patients. The authors evaluated combinations of bilirubin, ALP, and AST thresholds after one year of UDCA in 292 PBC patients to predict outcomes. Patients achieving ALP < 3 ULN, AST < 2 ULN, and bilirubin ≤ 1 mg/dL after one year of UDCA had a 90 % ten‑year transplant‑free survival versus 51 % for others, outperforming the Barcelona criteria, and independent predictors of death or transplantation included baseline bilirubin > 1 mg/dL, advanced histology, interface hepatitis, and lack of biochemical response.

Abstract

Biochemical response to ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis (PBC) is variable. It has been recently proposed that an alkaline phosphatase (ALP) decline of more than 40% in baseline value or a normal level after 1 year of UDCA treatment (Barcelona criteria) could serve as a good marker of long-term prognosis. Our aim was to define the best efficient set of biochemistries able to identify UDCA-treated patients at risk of death or liver transplantation (LT). The efficiency of several combinations of serum bilirubin, ALP, and aspartate aminotransferase (AST) threshold values to predict outcome was assessed after 1 year of treatment in 292 patients with PBC. Patients showing ALP <3 upper limit of normal (ULN), AST <2 ULN, and bilirubin </=1 mg/dL after 1 year of UDCA had a 10-year transplant-free survival rate of 90% (95% confidence interval, 81%-95%), compared to 51% (95% confidence interval, 38%-64%) for those who did not (P < 0.001). Patients were less well discriminated by the Barcelona criteria (79% versus 63%). Independent predictive factors of death or LT were baseline serum bilirubin level >1 mg/dL (relative risk [RR], 1.7), histologic stage >/=3 (RR, 1.5), interface hepatitis (RR, 1.9), and the absence of biochemical response (ALP >3 ULN or AST >2 ULN, or bilirubin >1 mg/dL) (RR, 2.3). Antinuclear antibodies against gp210 or Sp100 proteins were associated with death or LT in univariate but not in multivariate analysis.This study defines the best efficient biochemical response to UDCA, which, independent of baseline predictive factors, identifies patients with PBC with a good long-term prognosis. Patients who fail to achieve this response and those with interface hepatitis or advanced histological stage should be targeted for further therapeutic research.