Tu1002 Fenofibrate Improves Alkaline Phosphatase in Primary Sclerosing Cholangitis

Dejman, Adriana; Clark, Virginia; Martin, Paul; Levy, Cynthia

doi:10.1016/s0016-5085(13)63825-1

Cited by 12 publications

(13 citation statements)

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“…Serum ALP and ALT improved in 7 patients (64%). Use of fenofibrate was also evaluated for PSC in 2 small open‐label studies from France and the US published only in abstract format, again showing improvement of serum liver biochemistries . Additional studies including larger sample size and longer follow‐up are warranted.…”

Section: Novel Therapiesmentioning

confidence: 99%

Novel and emerging therapies for cholestatic liver diseases

Goldstein

Levy

2018

Liver International

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While bile acids are important for both digestion and signalling, hydrophobic bile acids can be harmful, especially when in high concentrations. Mechanisms for the protection of cholangiocytes against bile acid cytotoxicity include negative feedback loops via farnesoid X nuclear receptor (FXR) activation, the bicarbonate umbrella, cholehepatic shunting and anti-inflammatory signalling, among others. By altering or overwhelming these defence mechanisms, cholestatic diseases such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) can further progress to biliary cirrhosis, end-stage liver disease and death or liver transplantation. While PBC is currently treated with ursodeoxycholic acid (UDCA) and obeticholic acid (OCA), many fail treatment, and we have yet to find an effective therapy for PSC. Novel therapies under evaluation target nuclear and surface receptors including FXR, transmembrane G-protein-coupled receptor 5 (TGR5), peroxisome proliferator-activated receptor (PPAR) and pregnane X receptor (PXR). Modulation of these receptors leads to altered bile composition, decreased cytotoxicity, decreased inflammation and improved metabolism. This review summarizes our current understanding of the role of bile acids in the pathophysiology of cholestatic liver diseases, presents the rationale for already approved medical therapies and discusses novel pharmacologic therapies under investigation.

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Section: Novel Therapiesmentioning

confidence: 99%

Novel and emerging therapies for cholestatic liver diseases

Goldstein

Levy

2018

Liver International

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“…Overall, there was strong rationale to test fibrates as a therapeutic option in PSC patients, especially those with poor response to UDCA. Experience with fibrates in PSC is very scarce and is limited to small case series with short follow-up but preliminary results mostly from Japan appear encouraging [14][15][16][17]. Herein, we report on the combined experience of two European reference centers for chronic cholestatic liver diseases, evaluating the efficacy and safety of fibrates in PSC patients with incomplete biochemical response to UDCA.…”

Section: Introductionmentioning

confidence: 99%

Primary sclerosing cholangitis response to the combination of fibrates with ursodeoxycholic acid: French–Spanish experience

Lemoinne

Pares

Reig

et al. 2018

Clinics and Research in Hepatology and Gastroenterology

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“…In a previous study, the same group reported effect (ALP reduced by 30.4% [median -177] at 6 months) of bezafibrate 400 mg/day; ALP was reduced in 5/7 PSC patients [121]. In a small study of eight PSC patients only published as an abstract, fenofibrate was reported to induce significant reduction in ALP and ALT but no change in Mayo risk score at 6 months [124]. The larger French-Spanish study reported that fibrates (fenofibrate 200 mg/day or bezafibrate 400 mg/day for at least 6 months) in addition to UDCA in patients with ALP [ 1.5 9 ULN on UDCA alone, reduced ALP and ALT by 41% and 39% respectively at 3 months, as well as reduced pruritus in 20 PSC patients, with 40% of patients reaching ALP \ 1.5 9 ULN [123].…”

Section: Fibrates and Ppar Activationmentioning

confidence: 95%