Baseline ductopenia and treatment response predict long-term histological progression in primary biliary cirrhosis

Teru Kumagi, Maha Guindi, Sandra E Fischer, Tamara Arenovich, Rupert Abdalian, Catalina Coltescu, E Jenny Heathcote, Gideon M Hirschfield

Research output: Contribution to journalArticlepeer-review

195 Citations (Scopus)


OBJECTIVES: Laboratory and pathological predictors of future histological progression in primary biliary cirrhosis (PBC) are needed for routine practice and clinical trials. We sought to develop clinically meaningful markers for those with predominantly early disease at risk of progressive liver damage.

METHODS: Patients with PBC (n=69) with a follow-up liver biopsy performed approximately 10 years after initial histological diagnosis were identified and reviewed.

RESULTS: Histological progression in the stage of fibrosis observed in paired liver biopsies from the same patient was associated with the absence of biochemical response to ursodeoxycholic acid (UDCA) at 2 years: alkaline phosphatase (ALP) >1.67 × ULN (upper limit of normal) (P=0.001, odds ratio (OR) 12.14, 95% confidence interval (CI) 2.69-54.74) when defined as an increase in one stage and ALP > 1.76 × ULN (P=0.03, OR 5.07, 95% CI 1.17-21.95) when defined as an increase in two stages. Ductopenia (>50% loss), as formally evaluated through blinded biopsy review of liver tissue obtained at initial diagnosis in a subset of 34 patients, predicted histological progression (P=0.012), along with biochemical response to UDCA (P=0.002). The presence of interface hepatitis in the same biopsies did not.

CONCLUSIONS: Patients with PBC who fail to show a biochemical response to UDCA or who have ductopenia on baseline biopsy progress histologically during extended follow-up. Such patients may benefit from novel treatments, with our exploratory data providing a means of identifying these individuals early in their disease.

Original languageEnglish
Pages (from-to)2186-94
Number of pages9
JournalThe American Journal of Gastroenterology
Issue number10
Publication statusPublished - Oct 2010


  • Adult
  • Alkaline Phosphatase
  • Disease Progression
  • Female
  • Humans
  • Immunoglobulins
  • Liver
  • Liver Cirrhosis, Biliary
  • Male
  • Middle Aged
  • Odds Ratio
  • Patient Selection
  • Predictive Value of Tests
  • Regression Analysis
  • Retrospective Studies
  • Treatment Outcome
  • Ursodeoxycholic Acid


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