TY - JOUR
T1 - Factors Associated With Progression and Outcomes of Early Stage Primary Biliary Cholangitis
AU - Global Primary Biliary Cholangitis Study Group
AU - Gatselis, Nikolaos K.
AU - Goet, Jorn C.
AU - Zachou, Kalliopi
AU - Lammers, Willem J.
AU - Janssen, Harry L.A.
AU - Hirschfield, Gideon
AU - Corpechot, Christophe
AU - Lindor, Keith D.
AU - Invernizzi, Pietro
AU - Mayo, Marlyn J.
AU - Battezzati, Pier Maria
AU - Floreani, Annarosa
AU - Pares, Albert
AU - Lygoura, Vasiliki
AU - Nevens, Frederik
AU - Mason, Andrew L.
AU - Kowdley, Kris V.
AU - Ponsioen, Cyriel Y.
AU - Bruns, Tony
AU - Thorburn, Douglas
AU - Verhelst, Xavier
AU - Harms, Maren H.
AU - van Buuren, Henk R.
AU - Hansen, Bettina E.
AU - Dalekos, George N.
N1 - Funding Information:
Funding This investigator-initiated study was supported by unrestricted grants from Intercept Pharmaceuticals and was funded by the Foundation for Liver and Gastrointestinal Research (a not-for-profit foundation) in Rotterdam, The Netherlands. The supporting parties had no influence on the study design, data collection and analyses, writing of the manuscript, or the decision to submit the manuscript for publication.
Funding Information:
Conflicts of interest These authors disclose the following: Tony Bruns has received honoraria from Intercept Pharmaceuticals, Falk, and Norgine, and travel expenses from Gilead and Intercept Pharmaceuticals; Henk R. van Buuren received unrestricted grants from Intercept Pharmaceuticals; Christophe Corpechot is a consultant for Intercept Pharmaceuticals and Inventiva Pharma, receives grants from Intercept Pharmaceuticals and Arrow Generiques, and has lectured for GlaxoSmithKline; George N. Dalekos has served as an advisor/lecturer for AbbVie, Bristol-Myers Squibb, Gilead, Novartis, Bayer, and Roche, and has received grant support from Bristol-Myers Squibb, Gilead, and Roche; Annarosa Floreani has acted as advisor to the Primary Biliary Cholangitis Committee, sponsored by Intercept; Nikolaos K. Gatselis has served as an advisor/lecturer for AbbVie, Bristol-Myers Squibb, and Gilead; Bettina E. Hansen has received unrestricted grants from Intercept Pharmaceuticals, and is a consultant for Intercept Pharmaceuticals, CymaBay, and Janssen Pharma; Maren H. Harms has received a speaker's fee from Zambon; Gideon Hirschfield has acted as an advisor/consultant for GlaxoSmithKline, Novartis, CymaBay Therapeutics, Intercept Pharmaceuticals, and Falk; Pietro Invernizzi has received a speaker's fee from Zambon; Harry L. A. Janssen has received grants and acted as a consultant for AbbVie, Bristol Myers Squibb, Gilead Sciences, Janssen, Inc, Medimmune, Merck, Roche, Arbutus, and Vir Biotechnology; Andrew L. Mason is a consultant for Intercept Pharmaceuticals and has received research support from Intercept Pharmaceuticals, Merck Canada, AbbVie, and Gilead Sciences; Marlyn J. Mayo has received research grants from Intercept Pharmaceuticals; Albert Pares has acted as an advisor for Intercept Pharmaceuticals and Novartis; Cyriel Y. Ponsioen has received grant support from Takeda, speaker's fees from AbbVie, Takeda, and Dr Falk Pharma, and served as a consultant for Takeda; and Xavier Verhelst has served as a consultant for Intercept Pharmaceuticals, Gilead, MSD, and AbbVie, and received speaker's fees from Gilead, Bayer, MSD, and AbbVie. The remaining authors disclose no conflicts. Funding This investigator-initiated study was supported by unrestricted grants from Intercept Pharmaceuticals and was funded by the Foundation for Liver and Gastrointestinal Research (a not-for-profit foundation) in Rotterdam, The Netherlands. The supporting parties had no influence on the study design, data collection and analyses, writing of the manuscript, or the decision to submit the manuscript for publication.
Publisher Copyright:
© 2020 AGA Institute
PY - 2020/3
Y1 - 2020/3
N2 - Background & Aims: Patients usually receive a diagnosis of primary biliary cholangitis (PBC) at an early stage, based on biochemical analyses. We investigated the proportion of patients who progress to moderate or advanced PBC and factors associated with progression and patient survival. Methods: We obtained data from 1615 patients (mean age, 55.4 y) with early stage PBC (based on their normal levels of albumin and bilirubin), collected at the time of initial evaluation or treatment, from the Global PBC Study Group database (comprising patients at 19 liver centers in North American and European countries). We collected data from health care evaluations on progression to moderate PBC (abnormal level of bilirubin or albumin) or advanced-stage PBC (abnormal level of both). The median follow-up time was 7.9 years. The composite end point was decompensation, hepatocellular carcinoma, liver transplantation, or death. Results: Of the 1615 patients identified with early stage PBC, 904 developed moderate PBC and 201 developed advanced disease over the study period. The proportions of patients who transitioned to moderate PBC at 1, 3, and 5 years were 12.9%, 30.2%, and 45.8%. The proportions of these patients who then transitioned to advanced PBC at 1, 3, and 5 years later were 3.4%, 12.5%, and 16.0%, respectively. During the follow-up period, 236 patients had a clinical event. The proportions of patients with moderate PBC and event-free survival were 97.9%, 95.1%, and 91.5% at 1, 3, and 5 years, respectively, and the proportions of patients with advanced PBC and event-free survival were 90.6%, 71.2%, and 58.3% at 1, 3, and 5 years later, respectively. Variables associated with transition from early to moderate PBC included baseline levels of bilirubin, albumin, and alkaline phosphatase; aspartate to alanine aminotransferase ratio; platelet count; and treatment with ursodeoxycholic acid. Transitions from early to moderate PBC and from moderate to advanced PBC were associated with higher probabilities of a clinical event (time-dependent hazard ratios, 3.0; 95% CI, 2.0–4.5; and 4.6; 95% CI, 3.5–6.2). Conclusions: Approximately half of patients with early stage PBC progress to a more severe stage within 5 years. Progression is associated with an increased risk of a clinical event, so surveillance is important for patients with early stage PBC.
AB - Background & Aims: Patients usually receive a diagnosis of primary biliary cholangitis (PBC) at an early stage, based on biochemical analyses. We investigated the proportion of patients who progress to moderate or advanced PBC and factors associated with progression and patient survival. Methods: We obtained data from 1615 patients (mean age, 55.4 y) with early stage PBC (based on their normal levels of albumin and bilirubin), collected at the time of initial evaluation or treatment, from the Global PBC Study Group database (comprising patients at 19 liver centers in North American and European countries). We collected data from health care evaluations on progression to moderate PBC (abnormal level of bilirubin or albumin) or advanced-stage PBC (abnormal level of both). The median follow-up time was 7.9 years. The composite end point was decompensation, hepatocellular carcinoma, liver transplantation, or death. Results: Of the 1615 patients identified with early stage PBC, 904 developed moderate PBC and 201 developed advanced disease over the study period. The proportions of patients who transitioned to moderate PBC at 1, 3, and 5 years were 12.9%, 30.2%, and 45.8%. The proportions of these patients who then transitioned to advanced PBC at 1, 3, and 5 years later were 3.4%, 12.5%, and 16.0%, respectively. During the follow-up period, 236 patients had a clinical event. The proportions of patients with moderate PBC and event-free survival were 97.9%, 95.1%, and 91.5% at 1, 3, and 5 years, respectively, and the proportions of patients with advanced PBC and event-free survival were 90.6%, 71.2%, and 58.3% at 1, 3, and 5 years later, respectively. Variables associated with transition from early to moderate PBC included baseline levels of bilirubin, albumin, and alkaline phosphatase; aspartate to alanine aminotransferase ratio; platelet count; and treatment with ursodeoxycholic acid. Transitions from early to moderate PBC and from moderate to advanced PBC were associated with higher probabilities of a clinical event (time-dependent hazard ratios, 3.0; 95% CI, 2.0–4.5; and 4.6; 95% CI, 3.5–6.2). Conclusions: Approximately half of patients with early stage PBC progress to a more severe stage within 5 years. Progression is associated with an increased risk of a clinical event, so surveillance is important for patients with early stage PBC.
KW - Antimitochondrial Antibodies
KW - Autoimmune Liver Disease
KW - Prognostic Factor
KW - UDCA
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UR - http://www.scopus.com/inward/citedby.url?scp=85079379531&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2019.08.013
DO - 10.1016/j.cgh.2019.08.013
M3 - Article
C2 - 31419573
AN - SCOPUS:85079379531
SN - 1542-3565
VL - 18
SP - 684-692.e6
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 3
ER -