Alkaline phosphatase and liver fibrosis at diagnosis are associated with deep response to ursodeoxycholic acid in primary biliary cholangitis

Clin Res Hepatol Gastroenterol. 2024 Oct;48(8):102453. doi: 10.1016/j.clinre.2024.102453. Epub 2024 Aug 20.

Abstract

Objective: Primary biliary cholangitis is a chronic and progressive autoimmune liver disease, whose prognosis can be improved by normalizing alkaline phosphatase and bilirubin. While ursodeoxycholic acid (UDCA) is first line standard of care, approximately 40 % of patients exhibit incomplete response. We aimed to identify prognostic markers for deep response to UDCA therapy at presentation.

Patient and methods: Data from the Brazilian Cholestasis Study Group cohort were analyzed retrospectively. Patients were assessed for deep response, defined as normal alkaline phosphatase and bilirubin, after 1 year of UDCA treatment. Additionally, the performance of the UDCA response score in predicting deep response was evaluated.

Results: A total of 297 patients were analyzed, with 57.2 % achieving an adequate response according to the Toronto criteria, while 22.9 % reached deep response. Cirrhosis (OR 0.460; 95 % CI 0.225-0.942; p = 0.034) and elevated baseline alkaline phosphatase levels (OR 0.629; 95 % CI 0.513-0.770; p < 0.001) were associated with reduced odds of deep response. The UDCA response score exhibited moderate discrimination power (AUROC = 0.769) but lacked calibration.

Conclusions: Baseline ALP and liver fibrosis emerge as the most important prognostic factors to predict normalization of alkaline phosphatase and bilirubin after UDCA. The UDCA response score was inadequate for predicting deep response in the Brazilian PBC population.

Keywords: Biochemical remission; Biochemical response; Deep response; Predictive score; Prognosis; Risk stratification; Ursodeoxycholic acid.

MeSH terms

  • Adult
  • Aged
  • Alkaline Phosphatase* / blood
  • Bilirubin / blood
  • Cholagogues and Choleretics* / therapeutic use
  • Female
  • Humans
  • Liver Cirrhosis* / drug therapy
  • Liver Cirrhosis, Biliary / blood
  • Liver Cirrhosis, Biliary / complications
  • Liver Cirrhosis, Biliary / drug therapy
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Treatment Outcome
  • Ursodeoxycholic Acid* / therapeutic use

Substances

  • Ursodeoxycholic Acid
  • Alkaline Phosphatase
  • Cholagogues and Choleretics
  • Bilirubin