EVALUATION OF RESPONSE TO SECOND LINE THERAPY IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS AND INADEQUATE RESPONSE TO UDCA: A PILOT STUDY OF LIVER BIOPSIES FOLLOW UP

Abstract

Introduction and Objectives

Response to second line therapy is improvement of cholestatic parameters and prevention of fibrosis or liver events. AIM: to evaluate response at Month 12 and identify epidemiological, clinical and histological findings related to response.

Patients and Methods

50 patients initiating OCA (n=12), PPAR agonists (n=29) or combination of both (n=9) completed 12 months treatment and had baseline and M12 biopsy. Duct loss was evaluated with cytokeratin 7 and 19 and Scheuer staging applied. Biliary interface activity and bile duct damage recorded. Elastography was done at baseline and at 12 months. Statistical analysis using parametric t tests and 1-way ANOVA was performed.

Results

Mean age 53.6±10.6y and 84 % female. Mean ALP 388.8±166.6, ALT 71.3±40.6 and BT 0.9±0.4. 10 patients were cirrhotic. Response to second line therapy was 30 % with POISE criteria (n=15) and 14 % for ALP normalization (n=7). Male sex (p.04), moderate/severe ductopenia (p.01), elevated ALT (82 vs 46, p.003), bilirubin (1.07 vs 0.7, p.02) and cirrhosis (p.02) correlated with no response. Moderate/severe portal inflammation with interface hepatitis and lobular spilling was observed in 28 samples, irrespective of age and correlated with fibrosis. No patient with severe inflammation achieved response (n=5), and only 21% with moderate inflammation (n=5). On FU biopsies, response related with improvement of inflammation in 11 patients. Mild ductopenia did not affect response. No LFT predicted cirrhosis or portal inflammation. Cirrhosis at month 12 correlated with liver events in 5 patients resulting in 1 liver related death and 3 transplants. Elastography correlated with cirrhosis and liver events (10.4 vs 22.9, p<0.001) but not with inflammation or ductopenia.

Conclusions

Non response (70 %) related to male sex, cirrhosis, transaminases, moderate/severe inflammation and ductopenia. Cirrhosis and elastography correlated with liver events. Adverse histological findings suggest early second line intervention.