Long-Term Obeticholic Acid Therapy Improves Histological Endpoints in Patients With Primary Biliary Cholangitis

被引：88

作者：

Bowlus, Christopher L. ^{[1
]}

Pockros, Paul J. ^{[2
,3
]}

Kremer, Andreas E. ^{[4
]}

Pares, Albert ^{[5
]}

Forman, Lisa M. ^{[6
]}

Drenth, Joost P. H. ^{[7
]}

Ryder, Stephen D. ^{[8
]}

Terracciano, Luigi ^{[9
]}

Jin, Yuying ^{[10
]}

Liberman, Alexander ^{[10
]}

Pencek, Richard ^{[10
]}

Iloeje, Uche ^{[10
]}

MacConell, Leigh ^{[10
]}

Bedossa, Pierre ^{[11
]}

机构：

[1] Univ Calif Davis, Div Gastroenterol & Hepatol, 4150 St,Patient Support Serv Bldg 3500, Sacramento, CA 95817 USA

[2] Scripps Clin, Div Gastroenterol Hepatol, La Jolla, CA 92037 USA

[3] Scripps Translat Sci Inst, La Jolla, CA USA

[4] Friedrich Alexander Univ Erlangen Nurnberg, Dept Med 1, Erlangen, Germany

[5] Univ Barcelona, Ctr Invest Biomed Red Area Temat Enfermedades Hep, Inst Invest Biomed August Pi Sunyer, Hosp Clin, Barcelona, Spain

[6] Univ Colorado, Div Gastroenterol Hepatol, Aurora, CO USA

[7] Radboud Univ Nijmegen, Med Ctr, Dept Gastroenterol & Hepatol, Nijmegen, Netherlands

[8] Univ Nottingham, Nottingham Univ Hosp NHS Trust, Natl Inst Hlth Res, Nottingham Biomed Res Ctr, Nottingham, England

[9] Univ Basel, Dept Pathol, Basel, Switzerland

[10] Intercept Pharmaceut, San Diego, CA USA

[11] Univ Paris Diderot, Dept Pathol Physiol & Imaging, Paris, France

来源：

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY | 2020年 / 18卷 / 05期

关键词：

FXR Agonist; Farnesoid X Receptor Agonist; Liver Disease; Hepatic; URSODEOXYCHOLIC ACID; LIVER FIBROSIS; BIOCHEMICAL RESPONSE; GRADING SYSTEM; CIRRHOSIS; PROGRESSION; SURVIVAL; MANAGEMENT; BIOPSY; MODEL;

D O I：

10.1016/j.cgh.2019.09.050

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

BACKGROUND & AIMS: Primary biliary cholangitis (PBC) is an autoimmune disease characterized by bile duct destruction that can progress to cirrhosis. A liver biopsy substudy was conducted in the PBC obeticholic acid (OCA) International Study of Efficacy (POISE) to determine the long-term effects of OCA on liver damage and fibrosis in patients with PBC. POISE is a phase 3, double-blind, placebo-controlled, randomized trial with a 5-year open-label extension that evaluated 5 to 10 mg OCA daily in patients who were intolerant or unresponsive to ursodeoxycholic acid. METHODS: Liver biopsy specimens were collected from 17 patients at time of enrollment in the double-blind phase and after 3 years of OCA treatment. Histologic evaluations were performed by 2 pathologists in a blinded, randomized fashion to determine the effects of OCA on fibrosis and other histologic parameters. Collagen morphometry assessments were performed by automated second harmonic generation and 2-photon excitation microscopy to observe quantitative measures of fibrosis. RESULTS: From the time of enrollment until 3 years of treatment, most patients had improvements or stabilization in fibrosis (71%), bile duct loss (76%), ductopenia (82%), ductular reaction (82%), interface hepatitis (100%), and lobular hepatitis (94%). Over the 3-year period, we found significant reductions in collagen area ratio (median, -2.1; first quartile, -4.6, third quartile, -0.3; P = .013), collagen fiber density (median, -0.8; first quartile, -2.5; third quartile, 0; P = .021), collagen reticulation index (median, -0.1; first quartile, -0.3; third quartile, 0; P = .008), and fibrosis composite score (median, -1.0; first quartile, -2.5; third quartile, -0.5; P = .002). CONCLUSIONS: A subanalysis of data from the POISE study showed that long-term OCA treatment in patients with PBC is associated with improvements or stabilization of disease features, including ductular injury, fibrosis, and collagen morphometry feature

引用

页码：1170 / +

页数：15

共 37 条

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