{
  "abstract": "Aim 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.Method 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) (<130 units/L) and 2) ALP<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.Results Of 123 patients included, 95% were women. A statistically significant reduction in ALP was observed with both bezafibrate and fenofibrate from week 12 (p<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).Abstract P38 Table 1Comparative p values for UK-PBC score at 5, 10 and 15 years for Fenofibrate and Bezafibrate cohorts with ALP normalisation. IQR and p values included. Statistically significant results are in bold Bezafibrate and fenofibrate p value for UK-PBC score over time in patients with a normalised ALP 5 year 10 year 15 year Feno Beza Feno Beza Feno Beza Baseline-12 months 0.035* 0.015* 0.011* 0.015* 0.012* 0.014* Baseline-24 months 0.03* 0.039* 0.003* 0.057 0.03* 0.043* Baseline-36 months 0.03* 0.004* 0.036* 0.005* 0.031* 0.005* Baseline-48 months 0.007* 0.045* 0.007* 0.041* 0.007* 0.041* Baseline-60 months 0.006* 0.674 0.006* 0.674 0.006* 0.674 Baseline-120 months 0.31 0.655 0.31 0.655 0.31 0.655 Feno- Fenofibrate, Beza- Bezafibrate, n- number of patients, ALP- Alkaline PhosphataseDiscussion 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.",
  "authors": [
    {
      "affiliations": [
        "Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK",
        "Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK"
      ],
      "name": "Geraldine Carroll"
    },
    {
      "affiliations": [
        "Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK",
        "Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK"
      ],
      "name": "David Jones"
    },
    {
      "affiliations": [
        "Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK",
        "Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK"
      ],
      "name": "Jessica Dyson"
    }
  ],
  "title": "P38 Efficacy of fibrates as second line therapy in high-risk primary biliary cholangitis: a retrospective cohort study",
  "uid": "f4c25ae7-8870-57e7-a58b-26128b06d719"
}