Biochemical and Histological Effectiveness of Long-term Use of Fenofibrate for Asymptomatic Primary Biliary Cholangitis

Kazufumi DOHMEN, Hirofumi Tanaka, Masatora Haruno, Shinichi Aishima

Abstract


BACKGROUND/AIM: Ursodeoxycholic acid (UDCA) is currently the standard treatment for asymptomatic primary biliary cholangitis (aPBC). Potential favourable effects of fibrates have been demonstrated in aPBC patients exhibiting an incomplete response to UDCA. The mechanism of action of fibrates involves regulation of the expression of various lipids and proteins via the activation of peroxisome proliferator-activated receptor-α (PPAR-α). Among different fibrates, the binding activity of fenofibrate to PPAR-α is stronger than that of bezafibrate. However, whether fenofibrate is histologically effective for treating aPBC remains to be elucidated. The aim of this study was to evaluate the biochemical and histological effects of the long-term use of fenofibrate in patients with aPBC refractory to UDCA.

METHODS: Of 17 aPBC patients treated with fenofibrate plus UDCA, 13 patients treated for more than 36 months were involved in this study. Various characteristics of these 13 patients were compared between the time of initiation of fenofibarate treatment and 36 months after the administration of fenofibrate. Liver biopsy examinations were performed in five patients at the initial administration of fenofibrate and at approximately two and a half years (22~39 months) after the initiation of fenofibrate therapy. The histological stage was determined based on Scheuer’s classification and Nakanuma’s classification.

RESULTS: Among the patients treated with UDCA and fenofibrate, the serum alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γGTP) and serum IgM levels decreased from 524.6±190.8 to 218.7±74.8 IU/l, 192.7±87.1 to 29.5±17.5 IU/l and 391.4±244.0 to 166.3±115.3 mg/dl (p<0.0001), respectively. With regard to the histological findings of the liver, three cases of Scheuer’s stage 1 disease improved to portal inflammation, while two cases of Scheuer’s stage 1 or Scheuer’s stage 2 remained stable. Similarly, three cases of Nakanuma stage 2 improved to Nakanuma stage 1 and one case of Nakanuma stage 3 improved to stage 2. Although one case of Nakanuma stage 2 remained unchanged, the grading in that case improved from a hepatitis activity (HA) of 1 to HA0.

CONCLUSION: Combination therapy with fenofibrate plus UDCA results in significant biochemical and histological improvements in patients with aPBC. 

Limitation: Short follow-up, small number of samples, retrospective, single-center study.


Keywords


Fenofibrate, Fibrate, Primary Biliary Ciholangitis, Histology

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