Post-treatment LSM rather than change during treatment predicts decompensation in patients with cACLD after HCV cure
Georg Semmler, Sonia Alonso López, Mònica Pons, Sabela Lens, Elton Dajti, Marie Griemsmann, Alberto Zanetto, Lukas Burghart, Stefanie Hametner‐Schreil, Lukas Hartl, Marisa Manzano, Sergio Rodríguez‐Tajes, Paola Zanaga, Michael Schwarz, María Luisa Gutiérrez García, Mathias Jachs, Anna Pocurull, Benjamín Polo Lorduy, D. Ecker, Beatriz Muñoz, Sonia Izquierdo, Yolanda Real, Adriana Ahumada, David Bauer, Jim Benjamin Mauz, Michelle Casanova-Cabral, Michael Gschwantler, Francesco Paolo Russo, Francesco Azzaroli, Benjamin Maasoumy, Thomas Reiberger, Xavier Forns, Joan Genescà, Rafael Bañares, Mattias Mandorfer, S. Agostini, Lorenz Balcar, Sara Battistella, David Chromy, Markus Cornberg, Katja Deterding, Inmaculada Fernández, Conrado Fernández‐Rodríguez, Francisco Gea, Fiona Koeck, Julia Krawanja, Daniela Neumayer, Daniel Riado, Diego Rincón, Philipp Schwabl, Benedikt Simbrunner, Michael Trauner, Clara Uson, Heiner Wedemeyer
Abstract
BACKGROUND & AIMS: Baveno VII has defined a clinically significant (i.e., prognostically meaningful) decrease in liver stiffness measurement (LSM) in cACLD as a decrease of ≥20% associated with a final LSM <20 kPa or any decrease to <10 kPa. However, these rules have not yet been validated against direct clinical endpoints. METHODS: We retrospectively analysed patients with cACLD (LSM ≥10 kPa) with paired liver stiffness measurement (LSM) before (BL) and after (FU) HCV cure by interferon-free therapies from 15 European centres. The cumulative incidence of hepatic decompensation was compared according to these criteria, considering hepatocellular carcinoma and non-liver-related death as competing risks. RESULTS: A total of 2,335 patients followed for a median of 6 years were analysed. Median BL-LSM was 16.6 kPa with 37.1% having ≥20 kPa. After HCV cure, FU-LSM decreased to a median of 10.9 kPa (<10 kPa: 1,002 [42.9%], ≥20 kPa: 465 [19.9%]) translating into a median LSM change of -5.3 (-8.8 to -2.4) kPa corresponding to -33.9 (-48.0 to -15.9) %. Patients achieving a clinically significant decrease (65.4%) had a significantly lower risk of hepatic decompensation (subdistribution hazard ratio: 0.12, 95% CI 0.04-0.35, p <0.001). However, these risk differences were primarily driven by a negligible risk in patients with FU-LSM <10 kPa (5-year cumulative incidence: 0.3%) compared to a high risk in patients with FU-LSM ≥20 kPa (16.6%). Patients with FU-LSM 10-19.9 kPa (37.4%) also had a low risk of hepatic decompensation (5-year cumulative incidence: 1.7%), and importantly, the risk of hepatic decompensation did not differ between those with/without an LSM decrease of ≥20% (p = 0.550). CONCLUSIONS: FU-LSM is key for risk stratification after HCV cure and should guide clinical decision making. LSM dynamics do not hold significant prognostic information in patients with FU-LSM 10-19.9 kPa, and thus, their consideration is not of sufficient incremental value in the specific context of HCV cure. IMPACT AND IMPLICATIONS: Liver stiffness measurement (LSM) is increasingly applied as a prognostic biomarker and commonly decreases in patients with compensated advanced chronic liver disease achieving HCV cure. Although Baveno VII proposed criteria for a clinically significant decrease, little is known about the prognostic utility of LSM dynamics (changes through antiviral therapy). Interestingly, in those with a post-treatment LSM of 10-19.9 kPa, LSM dynamics did not provide incremental information, arguing against the consideration of LSM dynamics as prognostic criteria. Thus, post-treatment LSM should guide the management of patients with compensated advanced chronic liver disease achieving HCV cure.