Primary sclerosing cholangitis response to the combination of fibrates with ursodeoxycholic acid: French–Spanish experience - 03/12/18

Doi : 10.1016/j.clinre.2018.06.009

Sara Lemoinne ^a,^b , Albert Pares ^c , Anna Reig ^c , Karima Ben Belkacem ^a,^b , Astrid Donald Kemgang Fankem ^a,^b , Farid Gaouar ^a , Raoul Poupon ^a , Chantal Housset ^a,^b , Christophe Corpechot ^a,^b , Olivier Chazouillères ^a,^b,^⁎
^a Hepatology department, reference center for inflammatory biliary diseases and autoimmune hepatitis, Saint-Antoine Hospital, Assistance publique–Hôpitaux de Paris, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France
^b INSERM, Sorbonne université, centre de recherche Saint-Antoine (CRSA), faculté de médecine, site Saint-Antoine, 27, rue de Chaligny, 75012 Paris, France
^c IDIBAPS, CIBERehd, Liver Unit, Hospital Clínic, Univesity of Barcelona, Carrer de Villarroel, 170, 08036 Barcelona, Spain

^⁎Corresponding author at: Service d’hépatologie, hôpital Saint-Antoine, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France.Service d’hépatologie, hôpital Saint-Antoine184, rue du Faubourg-Saint-AntoineParis75012France

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Highlights

•

What is current knowledge?

∘	There is no medical treatment of proven efficacy in PSC.
∘	Fibrates improve pruritus and serum liver tests in patients with primary biliary cholangitis.

•

What is new here?

•

In PSC patients with incomplete response to UDCA, addition of fibrates:

∘	decreases ALP levels;
∘	improves pruritus.

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Summary

Background & aims

In patients with primary sclerosing cholangitis (PSC), ursodeoxycholic acid (UDCA) treatment improves serum liver tests and surrogate markers of prognosis but has no proven effect on survival. Additional therapies are obviously needed. Fibrates, PPAR agonists with anti-cholestatic properties, have a beneficial effect in primary biliary cholangitis. The aim of this study was to evaluate the safety and efficacy of fibrates in PSC patients.

Methods

Retrospectively, we investigated PSC patients treated with fibrates (fenofibrate 200mg/day or bezafibrate 400mg/day) for at least 6 months in addition to UDCA, after an incomplete biochemical response (alkaline phosphatase [ALP] ≥1.5×upper limit of normal) to UDCA. Changes in biochemical parameters and clinical features were assessed.

Results

Twenty patients were included (fourteen from Paris and six from Barcelona): median age 43.8 years, median liver stiffness 11kPa (≥F3). Upon treatment with fibrates (median duration of 1.56 years), liver tests significantly improved, including a reduction of ALP levels by 41% and pruritus significantly decreased. No serious adverse event attributable to fibrates occurred. Discontinuation of fibrates was followed by a clear rebound of ALP. Despite biochemical improvement, liver stiffness significantly increased.

Conclusions

Combining UDCA with fibrates results in a significant biochemical improvement and pruritus decrease in PSC patients with incomplete response to UDCA. These results provide a rationale for larger and prospectively designed studies to establish the efficacy and safety of fibrates in PSC.

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Keywords : Chronic liver diseases, Cholestasis, Liver fibrosis, Cirrhosis

Abbreviations : ALP, ALT, AST, CPK, GGT, IBD, LT, PBC, PPAR, PSC, SEM, UDCA, ULN