Additional fibrate treatment in UDCA-refractory PBC patients

Sung Won Chung, Jeong Hoon Lee, Minseok Albert Kim, Galam Leem, Sun Woong Kim, Young Chang, Hyo Young Lee, Jun Sik Yoon, Jun Yong Park, Yun Bin Lee, Eun Ju Cho, Su Jong Yu, Yoon Jun Kim, Jung Hwan Yoon

Research output: Contribution to journalArticle

Abstract

Background & Aims: There is no proven treatment for ursodeoxycholic acid (UDCA)-refractory primary biliary cholangitis (PBC) other than obeticholic acid. Although fibrates have been reported to improve biochemical parameters, the long-term effects remain unclear. This study evaluated the effect of fibrate on clinical outcomes of UDCA-refractory PBC. Methods: Patients whose alkaline phosphatase (ALP) was not normalized with at least 13 mg/kg of UDCA treatment for >1 year were included from two tertiary referral centres. The primary outcome was ALP normalization. Secondary outcomes included the development of cirrhosis and hepatic deterioration. Immortal time bias was adjusted using the Mantel-Byar method. Results: A total of 100 UDCA-refractory PBC patients were included: 71 patients received UDCA alone (the UDCA group) and 29 patients received UDCA plus additional fibrate treatment of 160 mg/d fenofibrate or 400 mg/d bezafibrate (the fibrate/UDCA group). During the follow-up period, the probability of ALP normalization was significantly higher in the fibrate/UDCA group (hazard ratio [HR] = 5.00, 95% confidence interval = 2.87-8.27, P < 0.001). Among 58 non-cirrhotic patients (43 in the UDCA group and 15 in the fibrate/UDCA group), 19 patients (44.1%) in the UDCA group and none in the fibrate/UDCA group developed cirrhosis (HR = 0.12, P = 0.04). Hepatic deterioration (Child-Pugh score increase or signs of decompensated cirrhosis) occurred in 17 patients (23.9%) of the UDCA group and none in the fibrate/UDCA group in which the difference was significant (HR = 0.12, P = 0.04). Conclusions: In patients with UDCA-refractory PBC, additional fibrate treatment is associated with a higher probability of ALP normalization and a lower risk of cirrhosis development and hepatic deterioration.

Original languageEnglish
Pages (from-to)1776-1785
Number of pages10
JournalLiver International
Volume39
Issue number9
DOIs
Publication statusPublished - 2019 Sep 1

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Fibric Acids
Ursodeoxycholic Acid
Cholangitis
Therapeutics
Alkaline Phosphatase
Liver Cirrhosis
Fibrosis
Bezafibrate
Fenofibrate

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Chung, S. W., Lee, J. H., Kim, M. A., Leem, G., Kim, S. W., Chang, Y., ... Yoon, J. H. (2019). Additional fibrate treatment in UDCA-refractory PBC patients. Liver International, 39(9), 1776-1785. https://doi.org/10.1111/liv.14165
Chung, Sung Won ; Lee, Jeong Hoon ; Kim, Minseok Albert ; Leem, Galam ; Kim, Sun Woong ; Chang, Young ; Lee, Hyo Young ; Yoon, Jun Sik ; Park, Jun Yong ; Lee, Yun Bin ; Cho, Eun Ju ; Yu, Su Jong ; Kim, Yoon Jun ; Yoon, Jung Hwan. / Additional fibrate treatment in UDCA-refractory PBC patients. In: Liver International. 2019 ; Vol. 39, No. 9. pp. 1776-1785.
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title = "Additional fibrate treatment in UDCA-refractory PBC patients",
abstract = "Background & Aims: There is no proven treatment for ursodeoxycholic acid (UDCA)-refractory primary biliary cholangitis (PBC) other than obeticholic acid. Although fibrates have been reported to improve biochemical parameters, the long-term effects remain unclear. This study evaluated the effect of fibrate on clinical outcomes of UDCA-refractory PBC. Methods: Patients whose alkaline phosphatase (ALP) was not normalized with at least 13 mg/kg of UDCA treatment for >1 year were included from two tertiary referral centres. The primary outcome was ALP normalization. Secondary outcomes included the development of cirrhosis and hepatic deterioration. Immortal time bias was adjusted using the Mantel-Byar method. Results: A total of 100 UDCA-refractory PBC patients were included: 71 patients received UDCA alone (the UDCA group) and 29 patients received UDCA plus additional fibrate treatment of 160 mg/d fenofibrate or 400 mg/d bezafibrate (the fibrate/UDCA group). During the follow-up period, the probability of ALP normalization was significantly higher in the fibrate/UDCA group (hazard ratio [HR] = 5.00, 95{\%} confidence interval = 2.87-8.27, P < 0.001). Among 58 non-cirrhotic patients (43 in the UDCA group and 15 in the fibrate/UDCA group), 19 patients (44.1{\%}) in the UDCA group and none in the fibrate/UDCA group developed cirrhosis (HR = 0.12, P = 0.04). Hepatic deterioration (Child-Pugh score increase or signs of decompensated cirrhosis) occurred in 17 patients (23.9{\%}) of the UDCA group and none in the fibrate/UDCA group in which the difference was significant (HR = 0.12, P = 0.04). Conclusions: In patients with UDCA-refractory PBC, additional fibrate treatment is associated with a higher probability of ALP normalization and a lower risk of cirrhosis development and hepatic deterioration.",
author = "Chung, {Sung Won} and Lee, {Jeong Hoon} and Kim, {Minseok Albert} and Galam Leem and Kim, {Sun Woong} and Young Chang and Lee, {Hyo Young} and Yoon, {Jun Sik} and Park, {Jun Yong} and Lee, {Yun Bin} and Cho, {Eun Ju} and Yu, {Su Jong} and Kim, {Yoon Jun} and Yoon, {Jung Hwan}",
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Chung, SW, Lee, JH, Kim, MA, Leem, G, Kim, SW, Chang, Y, Lee, HY, Yoon, JS, Park, JY, Lee, YB, Cho, EJ, Yu, SJ, Kim, YJ & Yoon, JH 2019, 'Additional fibrate treatment in UDCA-refractory PBC patients', Liver International, vol. 39, no. 9, pp. 1776-1785. https://doi.org/10.1111/liv.14165

Additional fibrate treatment in UDCA-refractory PBC patients. / Chung, Sung Won; Lee, Jeong Hoon; Kim, Minseok Albert; Leem, Galam; Kim, Sun Woong; Chang, Young; Lee, Hyo Young; Yoon, Jun Sik; Park, Jun Yong; Lee, Yun Bin; Cho, Eun Ju; Yu, Su Jong; Kim, Yoon Jun; Yoon, Jung Hwan.

In: Liver International, Vol. 39, No. 9, 01.09.2019, p. 1776-1785.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Additional fibrate treatment in UDCA-refractory PBC patients

AU - Chung, Sung Won

AU - Lee, Jeong Hoon

AU - Kim, Minseok Albert

AU - Leem, Galam

AU - Kim, Sun Woong

AU - Chang, Young

AU - Lee, Hyo Young

AU - Yoon, Jun Sik

AU - Park, Jun Yong

AU - Lee, Yun Bin

AU - Cho, Eun Ju

AU - Yu, Su Jong

AU - Kim, Yoon Jun

AU - Yoon, Jung Hwan

PY - 2019/9/1

Y1 - 2019/9/1

N2 - Background & Aims: There is no proven treatment for ursodeoxycholic acid (UDCA)-refractory primary biliary cholangitis (PBC) other than obeticholic acid. Although fibrates have been reported to improve biochemical parameters, the long-term effects remain unclear. This study evaluated the effect of fibrate on clinical outcomes of UDCA-refractory PBC. Methods: Patients whose alkaline phosphatase (ALP) was not normalized with at least 13 mg/kg of UDCA treatment for >1 year were included from two tertiary referral centres. The primary outcome was ALP normalization. Secondary outcomes included the development of cirrhosis and hepatic deterioration. Immortal time bias was adjusted using the Mantel-Byar method. Results: A total of 100 UDCA-refractory PBC patients were included: 71 patients received UDCA alone (the UDCA group) and 29 patients received UDCA plus additional fibrate treatment of 160 mg/d fenofibrate or 400 mg/d bezafibrate (the fibrate/UDCA group). During the follow-up period, the probability of ALP normalization was significantly higher in the fibrate/UDCA group (hazard ratio [HR] = 5.00, 95% confidence interval = 2.87-8.27, P < 0.001). Among 58 non-cirrhotic patients (43 in the UDCA group and 15 in the fibrate/UDCA group), 19 patients (44.1%) in the UDCA group and none in the fibrate/UDCA group developed cirrhosis (HR = 0.12, P = 0.04). Hepatic deterioration (Child-Pugh score increase or signs of decompensated cirrhosis) occurred in 17 patients (23.9%) of the UDCA group and none in the fibrate/UDCA group in which the difference was significant (HR = 0.12, P = 0.04). Conclusions: In patients with UDCA-refractory PBC, additional fibrate treatment is associated with a higher probability of ALP normalization and a lower risk of cirrhosis development and hepatic deterioration.

AB - Background & Aims: There is no proven treatment for ursodeoxycholic acid (UDCA)-refractory primary biliary cholangitis (PBC) other than obeticholic acid. Although fibrates have been reported to improve biochemical parameters, the long-term effects remain unclear. This study evaluated the effect of fibrate on clinical outcomes of UDCA-refractory PBC. Methods: Patients whose alkaline phosphatase (ALP) was not normalized with at least 13 mg/kg of UDCA treatment for >1 year were included from two tertiary referral centres. The primary outcome was ALP normalization. Secondary outcomes included the development of cirrhosis and hepatic deterioration. Immortal time bias was adjusted using the Mantel-Byar method. Results: A total of 100 UDCA-refractory PBC patients were included: 71 patients received UDCA alone (the UDCA group) and 29 patients received UDCA plus additional fibrate treatment of 160 mg/d fenofibrate or 400 mg/d bezafibrate (the fibrate/UDCA group). During the follow-up period, the probability of ALP normalization was significantly higher in the fibrate/UDCA group (hazard ratio [HR] = 5.00, 95% confidence interval = 2.87-8.27, P < 0.001). Among 58 non-cirrhotic patients (43 in the UDCA group and 15 in the fibrate/UDCA group), 19 patients (44.1%) in the UDCA group and none in the fibrate/UDCA group developed cirrhosis (HR = 0.12, P = 0.04). Hepatic deterioration (Child-Pugh score increase or signs of decompensated cirrhosis) occurred in 17 patients (23.9%) of the UDCA group and none in the fibrate/UDCA group in which the difference was significant (HR = 0.12, P = 0.04). Conclusions: In patients with UDCA-refractory PBC, additional fibrate treatment is associated with a higher probability of ALP normalization and a lower risk of cirrhosis development and hepatic deterioration.

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Chung SW, Lee JH, Kim MA, Leem G, Kim SW, Chang Y et al. Additional fibrate treatment in UDCA-refractory PBC patients. Liver International. 2019 Sep 1;39(9):1776-1785. https://doi.org/10.1111/liv.14165