Response to Ursodeoxycholic Acid May Be Assessed Earlier to Allow Second-Line Therapy in Patients with Unresponsive Primary Biliary Cholangitis

Dig Dis Sci. 2023 Feb;68(2):514-520. doi: 10.1007/s10620-022-07654-x. Epub 2022 Aug 22.


Background: Response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) has been traditionally assessed 1 to 2 years after treatment initiation. With the development of new drugs, some patients may benefit from an earlier introduction of second-line therapies.

Aims: This study aims to identify whether well-validated response criteria could correctly identify individuals likely to benefit from add-on second-line therapy at 6 months.

Methods: Analysis of a multicenter retrospective cohort which included only patients with clear-cut PBC.

Results: 206 patients with PBC (96.6% women; mean age 54 ± 12 years) were included. Kappa concordance was substantial for Toronto (0.67), Rotterdam (0.65), Paris 1 (0.63) and 2 (0.63) criteria at 6 and 12 months, whereas Barcelona (0.47) and POISE trial (0.59) criteria exhibited moderate agreement. Non-response rates to UDCA was not statistically different when assessed either at 6 or 12 months using Toronto, Rotterdam or Paris 2 criteria. Those differences were even smaller or absent in those subjects with advanced PBC. Mean baseline alkaline phosphatase was 2.73 ± 1.95 times the upper limit of normal (× ULN) among responders versus 5.05 ± 3.08 × ULN in non-responders (p < 0.001).

Conclusions: After 6 months of treatment with UDCA, the absence of response by different criteria could properly identify patients who could benefit from early addition of second-line therapies, especially in patients with advanced disease or high baseline liver enzymes levels.

Keywords: Primary biliary cholangitis; Second-line therapy; Treatment; Ursodeoxycholic acid.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cholagogues and Choleretics / therapeutic use
  • Female
  • Humans
  • Liver Cirrhosis, Biliary* / drug therapy
  • Male
  • Middle Aged
  • Retrospective Studies
  • Ursodeoxycholic Acid* / therapeutic use


  • Ursodeoxycholic Acid
  • Cholagogues and Choleretics