P38 Efficacy of fibrates as second line therapy in high-risk primary biliary cholangitis: a retrospective cohort study

<h3>Aim</h3> Primary Biliary Cholangitis (PBC) is a cholestatic liver condition which, left untreated or inadequately treated, can lead to cirrhosis, transplantation or death. Approximately 40% of patients do not respond to 1st-line therapy with ursodeoxycholic acid (UDCA). We assessed the efficacy of bezafibrate and fenofibrate as 2nd-line therapy for high risk PBC. <h3>Method</h3> A retrospective cohort study was performed in Newcastle-upon-Tyne Hospitals Trust. Patients receiving bezafibrate or fenofibrate were identified from pre-existing databases and data collected on demographics, biochemistry and adverse events up to 120 months of treatment. Biochemical response was assessed by: 1) normalisation of Alkaline Phosphatase (ALP) (&lt;130 units/L) and 2) ALP&lt;1.67 times upper limit of normal (ULN). The UK-PBC risk score was used to estimate risk of developing liver failure at 5-, 10- and 15-years following treatment. <h3>Results</h3> Of 123 patients included, 95% were women. A statistically significant reduction in ALP was observed with both bezafibrate and fenofibrate from week 12 (p&lt;0.001). Overall, 79 (64.2%) achieved normalisation of ALP; 51/78 (65.4%) on bezafibrate and 28/48 (58.3%) fenofibrate (p=0.48). Of the 51 patients achieving ALP normalisation on bezafibrate, 37/51 (72.5%) normalised within 6 months as compared to 18/28 (64.3%) with fenofibrate. This was not significantly different between the groups (p=0.424). Fenofibrate patients with ALP normalisation had a sustained, statistically significant reduction in median UK-PBC risk scores at 5/10/15 years from 12 to 60 months (p=0.006–0.045). As compared to bezafibrate, where significant improvement was seen from month 12 to 48 (p=0.004–0.045) (See table 1). Creatinine rise from baseline occurred in 9 patients (7.3%) with bezafibrate and 2 (1.6%) with fenofibrate (p=0.15). Fibrates were stopped in 8 (6.5%) with bezafibrate dose reduction in 3 (2.4%). Creatinine returned to baseline in 10 (90.9%) on cessation of fibrate. Transaminitis occurred in 2 (2.5%) on bezafibrate and 1(2.1%) on fenofibrate (p=0.86). All resolved on cessation of therapy. Mean treatment duration prior to liver injury was 21.5 months (Range 11–32 months). <h3>Discussion</h3> Fibrates improve ALP within 3–6 months of treatment, with a sustained effect over time. This suggests treatment response should be assessed earlier than 1 year (which is stipulated timepoint in current guidelines). Changes in the UK-PBC risk score, suggest improved prognosis with both fibrates, especially in those with ALP normalisation. The risk of renal impairment necessitates caution and close monitoring, especially in those with pre-existing kidney disease.