Investigation into the efficacy of bezafibrate against primary biliary cirrhosis, with histological references from cases receiving long term monotherapy

Kurihara, Toshio; Maeda, Akiko; Shigemoto, Mutsuo; Yamashita, Katsuko; Hashimoto, Etsuko

doi:10.1111/j.1572-0241.2002.05413.x

Cited by 52 publications

(23 citation statements)

References 11 publications

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“…L-FABP is known as a major bile acid transporter [49,50], and the enhancement of its expression may be implicated in facilitation of intracellular bile acid mobility. Recently, the efficacy of bezafibrate has been demonstrated in patients with chronic cholestatic liver diseases, such as primary biliary cirrhosis [51][52][53]. The present results concerning L-FABP induction might partially explain the beneficial effects of bezafibrate against such diseases.…”

Section: Discussionsupporting

confidence: 50%

Cholesterol-lowering effect of bezafibrate is independent of peroxisome proliferator-activated receptor activation in mice

Nakajima

Tanaka

Sugiyama

et al. 2008

Biochemical Pharmacology

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Section: Discussionsupporting

confidence: 50%

Cholesterol-lowering effect of bezafibrate is independent of peroxisome proliferator-activated receptor activation in mice

Nakajima

Tanaka

Sugiyama

et al. 2008

Biochemical Pharmacology

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“…Recently, Kurihara et al has reported that the treatment of PBC with bezafibrate led to a sustained improvement in the levels of hepatobiliary enzymes and IgM during a relatively long period of monotherapy (10). We have speculated about the beneficial effects of fibrates with regard to the activation of PPARα.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it has been reported that fibrates are effective for the treatment of cholestatic diseases such as primary biliary cirrhosis (PBC) (9)(10)(11). Several lines of evidence indicate that fibrates have beneficial effects in PBC patients, but their mechanism of action is not known.…”

Section: Introductionmentioning

confidence: 99%

A Nuclear Receptor-mediated Choleretic Action of Fibrates is Associated with Enhanced Canalicular Membrane Fluidity and Transporter Activity Mediating Bile Acid-independent Bile Secretion

Nishioka

Hyogo

Numata

et al. 2005

JAT

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Fibrates are commonly used lipid-lowering agents that act via PPARα α α α α, a member of the nuclear hormone receptor superfamily. The mechanism(s) of fibrate-induced changes in the hepatic canalicular membrane and bile lipids are still unknown. Therefore, the aim of this study was to investigate the influence of fibrates on hepatic lipid metabolism and to assess the hepatocellular cytoprotective effect on hepatocyte canalicular membrane. Male ICR mice were fed standard chow with or without bezafibrate (100 mg/kg) for 6 days. The expression of canalicular membrane transporters (Mdr2 and Mrp2) was evaluated by RT-PCR and Western blotting. Canalicular membrane fluidity was also investigated. Canalicular membrane fluidity was markedly increased by fibrates. The expression of mdr 2 and mrp2 mRNA and protein showed a significant increase in fibrate-treated mice. These results suggested that fibrates improve liver function by enhancing bile secretion. The mechanism of the choleretic action of fibrate therapy might involve the enhancement of bile acid-independent bile secretion, since increased expression of Mdr2 and Mrp2 was found in fibrate-treated animals. These changes were very likely mediated by PPARα α α α α, and the increase of canalicular membrane fluidity may have been partly associated with enhancement of this transporter activity. J Atheroscler Thromb, 2005; 12: 211-217.

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“…Despite improving surrogate markers of long-term prognosis, the depth of evidence supporting fibrates in PBC remains small, with many trials employing undefined biochemical endpoints as a measure of treatment success, and only a few applying standardized criteria with relatively short duration (<1 year). The effects on histological progression are also unclear; some studies reporting improvement whereas others a deterioration [Yano et al 2002;Kurihara et al 2002]. Given that preliminary data have been promising, further studies should be encouraged.…”

Section: Fibric Acid Derivatesmentioning

confidence: 99%

Treatment of autoimmune liver disease: current and future therapeutic options

Trivedi

Hirschfield

2013

Therapeutic Advances in Chronic Disease

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Autoimmune liver disease spans three predominant processes, from the interface hepatitis of autoimmune hepatitis to the lymphocytic cholangitis of primary biliary cirrhosis, and finally the obstructive fibrosing sclerotic cholangiopathy of primary sclerosing cholangitis. Although all autoimmune in origin, they differ in their epidemiology, presentation and response to immunosuppressive therapy and bile acid based treatments. With an ongoing better appreciation of disease aetiology and pathogenesis, treatment is set ultimately to become more rational. We provide an overview of current and future therapies for patients with autoimmune liver disease, with an emphasis placed on some of the evidence that drives current practice.

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Investigation into the efficacy of bezafibrate against primary biliary cirrhosis, with histological references from cases receiving long term monotherapy

Cited by 52 publications

References 11 publications

Cholesterol-lowering effect of bezafibrate is independent of peroxisome proliferator-activated receptor activation in mice

Cholesterol-lowering effect of bezafibrate is independent of peroxisome proliferator-activated receptor activation in mice

A Nuclear Receptor-mediated Choleretic Action of Fibrates is Associated with Enhanced Canalicular Membrane Fluidity and Transporter Activity Mediating Bile Acid-independent Bile Secretion

Treatment of autoimmune liver disease: current and future therapeutic options

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