TY - JOUR
T1 - Long-Term Obeticholic Acid Therapy Improves Histological Endpoints in Patients With Primary Biliary Cholangitis
AU - Bowlus, Christopher L.
AU - Pockros, Paul J.
AU - Kremer, Andreas E.
AU - Parés, Albert
AU - Forman, Lisa M.
AU - Drenth, Joost P. H.
AU - Ryder, Stephen D.
AU - Terracciano, Luigi
AU - Jin, Yuying
AU - Liberman, Alexander
AU - Pencek, Richard
AU - Iloeje, Uche
AU - MacConell, Leigh
AU - Bedossa, Pierre
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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 features (ClinicalTrials.gov no: NCT01473524 and EudraCT no: 2011-004728-36).
AB - 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 features (ClinicalTrials.gov no: NCT01473524 and EudraCT no: 2011-004728-36).
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85078096120&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31606455
U2 - https://doi.org/10.1016/j.cgh.2019.09.050
DO - https://doi.org/10.1016/j.cgh.2019.09.050
M3 - Article
C2 - 31606455
SN - 1542-3565
VL - 18
SP - 1170-1178.e6
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 5
ER -