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NEW INSIGHTS FROM FOLLOW-UP LIVER BIOPSIES 10 YEARS AFTER DIAGNOSIS OF PRIMARY BILIARY CIRRHOSIS
T Kumagi1, R Abdalian1, M Guindi2, EJ Heathcote1
1Departments of Medicine, 2Pathology, UHN, University of Toronto
BACKGROUND: Primary Biliary Cirrhosis (PBC) runs a variable course. Biomarkers that predict likely disease progression are needed.
AIM: To identify early characteristics that may serve as markers of disease progression in PBC.
METHODS: A chart review of PBC patients with a repeat liver biopsy after initial histological diagnosis. Retrievable dual biopsies were reevaluated blinded to date for degree of fibrosis, portal inflammation, eosinophilic infiltration, interface hepatitis, lobular hepatitis, lobular necrosis, granulomas, feathery degeneration, ductopenia, duct injury by lymphocytes, florid duct lesions and ductular reaction. Definition of response to ursodeoxycholic acid (UDCA) was: complete responder (CR) normalization of alkaline phosphatase (ALP) within 2 years of initiating therapy, non-responder (NR) less than 50% decline of ALP, partial responder (PR) between CR and NR. Statistical analyses used either paired t tests, Mann-Whitney U test, chi-squared test, Fisher’s exact test, Kruskal Wallis test or ANOVAs with Bonferroni-adjusted pair wise comparisons.
RESULTS: Mean age (56 patients) at baseline was 46 ± 9 (range 30-61), 52 (92.9%) female and 45 (80.4%) AMA positive. All but one received UDCA with CR or PR response in 38 (69.1%), and 17 (30.9%) were NR. On the initial liver biopsy report, 6 (10.7%), 26 (46.4%), 13 (23.2%), 9 (16.1%) and 2 (3.6%) patients had stage 0, 1, 2, 3 and 4 of fibrosis, respectively. Repeat biopsies performed 9.2 ± 2.5 years after their initial biopsy showed NRs to UDCA therapy had more fibrosis progression (14 out of 17, p=0.006). Baseline ALT values in those with fibrosis progression were higher than in those without (114 ± 91 IU/l vs. 73 ± 52 IU/l, p=0.045). Baseline serum gp210 titers were higher with fibrosis progression than without (21.3 ± 35.1 U vs. 8.3 ± 13.9 U, p=0.046) and correlated with response to UDCA (CR: 3.9 ± 0.3 U, PR: 8.6 ± 14.2 U, NR: 36.1 ± 43.8 U, p=0.004). Re-review of 22 retrievable dual biopsies indicated that both interface hepatitis (p=0.037) and ductopenia (p=0.003) on initial biopsy correlated with NR to UDCA but not with fibrosis progression.
SUMMARY: Higher ALT and gp210 titer at baseline and failure to achieve a biochemical response with UDCA are associated with fibrosis progression in PBC. Both interface hepatitis and ductopenia may predict responsiveness to UDCA but not fibrosis progression, this latter finding may due to the small sample size.