Background: ELF score is a non-invasive assessment for NASH fibrosis. We assessed associations between ELF, clinical outcomes and PROs in advanced NASH.
Methods: NASH patients with advanced fibrosis (Stage ≥F3) were enrolled in 4 clinical trials of simtuzumab and selonsertib - neither showed efficacy. Liver biopsies, ELF scores, and PROs were collected at baseline and week 48. Disease progression (histologic progression to cirrhosis, hepatic decompensation, listed for or liver transplanted, death) was monitored over time (median 16 months; IQR 14-20 months).
Results: Patients (n=2155) with biopsy-proven advanced NASH [ 52.5% F4, 40% male, 78% white, 72% type 2 diabetes, mean baseline ELF 10.4±1.1 (F4: 11.4±1.2 vs. F3: 10.3±1.0, p<0.0001)] were included;16.7% F3-NASH had disease progression (96% progressed to cirrhosis or clinical symptoms); 7.3% F4-NASH experienced clinical events (39% ascites, 24% hepatic encephalopathy). Those who progressed had higher baseline ELF: 10.6 ± 1.0 vs. 9.9 ± 0.9 (F3) and 11.5 ± 1.2 vs. 10.6 ± 1.0 (F4) (both p<0.0001). In F3 and F4 patients, baseline ELF was independently associated with disease progression: adjusted hazard ratio (aHR) = 2.48 (2.11-2.93) and 2.83 (2.20-3.63) per 1 ELF point (p<0.0001). After adjustment for baseline ELF, increases in ELF were associated with disease progression: aHR (F3)=1.47 (1.20-1.80) and (F4)=1.68 (1.21-2.33) per +1 additional ELF point (both p<0.002). ELF scores were associated with PRO impairments- ELF cutoff of 10.43 described 18/23 PRO scores (p<0.05) including all domains of CLDQ-NASH. The average magnitude of PRO impairment was -6.1% of a PRO range in NASH with ELF≥10.43 vs. ELF<10.43. Patients with a decrease in ELF of at least 0.83 points had improvement in 11/23 PROs (all domains of CLDQ-NASH, up to +9.8%, p≤0.05).
Conclusions: ELF at baseline and its changes over time are good predictors of adverse clinical and PROs in advanced NASH.
Z. Younossi: Consultant; Self; AbbVie Inc., Bristol-Myers Squibb, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Novo Nordisk Inc., Terns and Viking. Q. Anstee: Consultant; Self; 89Bio, Abbott Laboratories, Acuitas Medical, Allergan/Tobira, AstraZeneca, Axcella, Blade, BNN Cardio, Celgene, Cirius, CymaBay, EcoR1, E3Bio, Eli Lilly & Company Ltd., Galmed, Genentech, Genfit S, Intercept Pharma Europe Ltd., Inventiva, IQVIA, Janssen, Madrigal, MedImmune, Metacrine, NewGene, NGMBio, North Sea Therapeutics, Novartis, Novo Nordisk A/S, Pfizer Ltd., Poxel, ProSciento, Raptor Pha. Research Support; Self; Abbvie, Allergan/Tobira, AstraZeneca, GlaxoSmithKline, Glympse Bio, Novartis Pharma AG, Pfizer Ltd., Vertex. Speaker’s Bureau; Self; Abbott Laboratories, Allergan/Tobira, BMS, Clinical Care Options, Falk, Fishawack, Genfit SA, Gilead, Integritas Communications, Kenes, MedScape. M. Trauner: Advisory Panel; Self; Gilead Sciences, Inc. Research Support; Self; Gilead Sciences, Inc. Speaker’s Bureau; Self; Gilead Sciences, Inc. Other Relationship; Self; Gilead Sciences, Inc. V.W.S. Wong: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Gilead Sciences, Inc. Consultant; Self; AbbVie Inc., Allergan plc., Echosens, Intercept Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Pfizer Inc. M. Camargo: Employee; Self; Gilead Sciences, Inc. L. Henry: None. M. Stepanova: None. M. Romero-Gomez: Consultant; Self; Kaleido Biosciences, Merck & Co., Inc., Novo Nordisk Inc., Siemens Corporation, Zydus Pharmaceuticals, Inc. E. Lawitz: None. R. Myers: None.
Gilead Sciences Foundation