TY - JOUR
T1 - Liver stiffness measurement by vibration-controlled transient elastography improves outcome prediction in primary biliary cholangitis
AU - Corpechot, Christophe
AU - Carrat, Fabrice
AU - Global & ERN Rare-Liver PBC Study Groups
AU - Gaouar, Farid
AU - Chau, Frederic
AU - Hirschfield, Gideon
AU - Gulamhusein, Aliya
AU - Montano-Loza, Aldo J.
AU - Lytvyak, Ellina
AU - Schramm, Christoph
AU - Pares, Albert
AU - Olivas, Ignasi
AU - Eaton, John E.
AU - Osman, Karim T.
AU - Dalekos, George
AU - Gatselis, Nikolaos
AU - Nevens, Frederik
AU - Cazzagon, Nora
AU - Zago, Alessandra
AU - Russo, Francesco Paolo
AU - Abbas, Nadir
AU - Trivedi, Palak
AU - Thorburn, Douglas
AU - Saffioti, Francesca
AU - Barkai, Laszlo
AU - Roccarina, Davide
AU - Calvaruso, Vicenza
AU - Fichera, Anna
AU - Delamarre, Adèle
AU - Medina-Morales, Esli
AU - Bonder, Alan
AU - Patwardhan, Vilas
AU - Rigamonti, Cristina
AU - Carbone, Marco
AU - Invernizzi, Pietro
AU - Cristoferi, Laura
AU - van der Meer, Adriaan
AU - de Veer, Rozanne
AU - Zigmond, Ehud
AU - Yehezkel, Eyal
AU - Kremer, Andreas E.
AU - Deibel, Ansgar
AU - Dumortier, Jérôme
AU - Bruns, Tony
AU - Große, Karsten
AU - Pageaux, Georges Philippe
AU - Wetten, Aaron
AU - Dyson, Jessica
AU - Jones, David
AU - Chazouillères, Olivier
AU - Hansen, Bettina
AU - de Ledinghen, V
N1 - Funding Information:
Dr. Corpechot reports receiving grants from Arrow and Intercept France, consulting fees from Intercept France, Inventiva Pharma, Cymabay and Genkyotex, and fees for teaching from Intercept France and GlaxoSmithKline France; Dr. Chazouillères, receiving grant support from Aptalis, fees for teaching from Mayoly Spindler, consulting fees from Genfit, and fees for teaching and consulting fees from Intercept; Dr. Schramm, receiving lecture fees from Falk Pharma; Dr. Dumortier, receiving consulting and teaching fees from Intercept France; Dr. Parés, receiving grant funding, speaking fees, and advisory board fees from Intercept, advisory board fees and speaking fees from Novartis, and speaking fees from CymaBay and Inova Diagnostics; Dr. Bruns reports receiving advisory board fees from Intercept, Grifols and Sobi and receiving speaking fees from Falk Foundation, Abbvie, CSL Behring, Intercept, Merck and Gilead. No other potential conflict of interest relevant to this article was reported.
Publisher Copyright:
© 2022 European Association for the Study of the Liver
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Background & Aims: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) has been shown to predict outcomes of patients with primary biliary cholangitis (PBC) in small-size studies. We aimed to validate the prognostic value of LSM in a large cohort study. Methods: We performed an international, multicentre, retrospective follow-up study of 3,985 patients with PBC seen at 23 centres in 12 countries. Eligibility criteria included at least 1 reliable LSM by VCTE and a follow-up ≥ 1 year. Independent derivation (n = 2,740) and validation (n = 568) cohorts were built. The primary endpoint was time to poor clinical outcomes defined as liver-related complications, liver transplantation, or death. Hazard ratios (HRs) with CIs were determined using a time-dependent multivariable Cox regression analysis. Results: LSM was independently associated with poor clinical outcomes in the derivation (5,324 LSMs, mean follow-up 5.0 ± 3.1 years) and validation (1,470 LSMs, mean follow-up 5.0 ± 2.8 years) cohorts: adjusted HRs (95% CI) per additional kPa were 1.040 (1.026–1.054) and 1.042 (1.029–1.056), respectively (p <0.0001 for both). Adjusted C-statistics (95% CI) at baseline were 0.83 (0.79–0.87) and 0.92 (0.89–0.95), respectively. Between 5 and 30 kPa, the log-HR increased as a monotonic function of LSM. The predictive value of LSM was stable in time. LSM improved the prognostic ability of biochemical response criteria, fibrosis scores, and prognostic scores. The 8 kPa and 15 kPa cut-offs optimally separated low-, medium-, and high-risk groups. Forty percent of patients were at medium to high risk according to LSM. Conclusions: LSM by VCTE is a major, independent, validated predictor of PBC outcome. Its value as a surrogate endpoint for clinical benefit in PBC should be considered. Lay summary: Primary biliary cholangitis (PBC) is a chronic autoimmune disease, wherein the body's immune system mistakenly attacks the bile ducts. PBC progresses gradually, so surrogate markers (markers that predict clinically relevant outcomes like the need for a transplant or death long before the event occurs) are often needed to expedite the drug development and approval process. Herein, we show that liver stiffness measurement is a strong predictor of clinical outcomes and could be a useful surrogate endpoint in PBC trials.
AB - Background & Aims: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) has been shown to predict outcomes of patients with primary biliary cholangitis (PBC) in small-size studies. We aimed to validate the prognostic value of LSM in a large cohort study. Methods: We performed an international, multicentre, retrospective follow-up study of 3,985 patients with PBC seen at 23 centres in 12 countries. Eligibility criteria included at least 1 reliable LSM by VCTE and a follow-up ≥ 1 year. Independent derivation (n = 2,740) and validation (n = 568) cohorts were built. The primary endpoint was time to poor clinical outcomes defined as liver-related complications, liver transplantation, or death. Hazard ratios (HRs) with CIs were determined using a time-dependent multivariable Cox regression analysis. Results: LSM was independently associated with poor clinical outcomes in the derivation (5,324 LSMs, mean follow-up 5.0 ± 3.1 years) and validation (1,470 LSMs, mean follow-up 5.0 ± 2.8 years) cohorts: adjusted HRs (95% CI) per additional kPa were 1.040 (1.026–1.054) and 1.042 (1.029–1.056), respectively (p <0.0001 for both). Adjusted C-statistics (95% CI) at baseline were 0.83 (0.79–0.87) and 0.92 (0.89–0.95), respectively. Between 5 and 30 kPa, the log-HR increased as a monotonic function of LSM. The predictive value of LSM was stable in time. LSM improved the prognostic ability of biochemical response criteria, fibrosis scores, and prognostic scores. The 8 kPa and 15 kPa cut-offs optimally separated low-, medium-, and high-risk groups. Forty percent of patients were at medium to high risk according to LSM. Conclusions: LSM by VCTE is a major, independent, validated predictor of PBC outcome. Its value as a surrogate endpoint for clinical benefit in PBC should be considered. Lay summary: Primary biliary cholangitis (PBC) is a chronic autoimmune disease, wherein the body's immune system mistakenly attacks the bile ducts. PBC progresses gradually, so surrogate markers (markers that predict clinically relevant outcomes like the need for a transplant or death long before the event occurs) are often needed to expedite the drug development and approval process. Herein, we show that liver stiffness measurement is a strong predictor of clinical outcomes and could be a useful surrogate endpoint in PBC trials.
UR - http://www.scopus.com/inward/record.url?scp=85137409865&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2022.06.017
DO - 10.1016/j.jhep.2022.06.017
M3 - Article
C2 - 35777587
AN - SCOPUS:85137409865
VL - 77
SP - 1545
EP - 1553
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 6
ER -