Zobair M Younossi1, Quentin M Anstee2, Vincent Wai-Sun Wong3, Michael Trauner4, Eric J Lawitz5, Stephen A Harrison6, Marianne Camargo7, Kathryn Kersey7, G Mani Subramanian7, Robert P Myers7, Maria Stepanova8. 1. Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia; Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Virginia. Electronic address: zobair.younossi@inova.org. 2. Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom; Newcastle National Institute for Health Research Biomedical Research Centre, Newcastle Upon Tyne Hospitals National Health Service Foundation Trust, Newcastle Upon Tyne, UK. 3. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong. 4. Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria. 5. Texas Liver Institute, University of Texas Health San Antonio, San Antonio, Texas. 6. Pinnacle Clinical Research, San Antonio, Texas. 7. Gilead Sciences, Inc, Foster City, California. 8. Center for Outcomes Research in Liver Disease, Washington DC.
Abstract
BACKGROUND & AIM: Fibrosis is an independent predictor of death in nonalcoholic steatohepatitis (NASH). We assessed the associations between histologic and noninvasive tests (NITs) for fibrosis with clinical and patient-reported outcomes (PROs) in advanced NASH. METHODS: Patients with advanced NASH (NASH Clinical Research Network stage F3 or F4) were enrolled in 4 multinational clinical trials of simtuzumab and selonsertib. Liver biopsy samples, NIT results, and PROs (Short Form-36, Chronic Liver Disease Questionnaire-NASH, EuroQol-5D, and Work Productivity and Activity Impairment) were prospectively collected. RESULTS: A total of 2154 patients with advanced NASH were included: 52.5% with F4 NASH, 40% male, 72% with type 2 diabetes, baseline liver stiffness of 24.1 ± 14.2 kPa in F4 disease and 14.6 ± 8.0 kPa in F3 disease, baseline mean Enhanced Liver Fibrosis score of 11.4 ± 1.2 in F4 disease and 10.3 ± 1.0 in F3 disease, and a median follow-up of 16 months. Of those with baseline F3 disease, 16.7% experienced disease progression to cirrhosis, whereas for those with F4 disease, 7.3% experienced clinical events (39% ascites, 24% hepatic encephalopathy); patients who progressed had higher baseline NIT scores (all P < .0001). Adjusted for baseline levels, increases in NIT scores were also associated with increased risk of disease progression in both the F3 and F4 groups (P < .01 for all NITs in F3 and for ELF, NAFLD Fibrosis Score, Fibrosis-4 (FIB-4), and liver stiffness in F4). Higher NIT scores were found to be associated with impairment in PROs: ELF, ≥10.43; Nonalcoholic Fatty Liver Disease Fibrosis Score, ≥1.80; Fibrotest score, ≥0.54; liver stiffness, ≥23.4 kPa. During treatment, patients with decreases in NIT scores experienced improvement of their PRO scores, whereas those with increase in NIT scores had their PRO scores worsen (P < .05). CONCLUSIONS: Baseline NIT scores and their changes over time are predictors of adverse clinical and PROs in patients with advanced NASH. (ClinicalTrials.gov, Numbers NCT01672866, NCT01672879, NCT03053050, and NCT03053063).
BACKGROUND & AIM: Fibrosis is an independent predictor of death in nonalcoholic steatohepatitis (NASH). We assessed the associations between histologic and noninvasive tests (NITs) for fibrosis with clinical and patient-reported outcomes (PROs) in advanced NASH. METHODS:Patients with advanced NASH (NASH Clinical Research Network stage F3 or F4) were enrolled in 4 multinational clinical trials of simtuzumab and selonsertib. Liver biopsy samples, NIT results, and PROs (Short Form-36, Chronic Liver Disease Questionnaire-NASH, EuroQol-5D, and Work Productivity and Activity Impairment) were prospectively collected. RESULTS: A total of 2154 patients with advanced NASH were included: 52.5% with F4 NASH, 40% male, 72% with type 2 diabetes, baseline liver stiffness of 24.1 ± 14.2 kPa in F4 disease and 14.6 ± 8.0 kPa in F3 disease, baseline mean Enhanced Liver Fibrosis score of 11.4 ± 1.2 in F4 disease and 10.3 ± 1.0 in F3 disease, and a median follow-up of 16 months. Of those with baseline F3 disease, 16.7% experienced disease progression to cirrhosis, whereas for those with F4 disease, 7.3% experienced clinical events (39% ascites, 24% hepatic encephalopathy); patients who progressed had higher baseline NIT scores (all P < .0001). Adjusted for baseline levels, increases in NIT scores were also associated with increased risk of disease progression in both the F3 and F4 groups (P < .01 for all NITs in F3 and for ELF, NAFLD Fibrosis Score, Fibrosis-4 (FIB-4), and liver stiffness in F4). Higher NIT scores were found to be associated with impairment in PROs: ELF, ≥10.43; Nonalcoholic Fatty Liver Disease Fibrosis Score, ≥1.80; Fibrotest score, ≥0.54; liver stiffness, ≥23.4 kPa. During treatment, patients with decreases in NIT scores experienced improvement of their PRO scores, whereas those with increase in NIT scores had their PRO scores worsen (P < .05). CONCLUSIONS: Baseline NIT scores and their changes over time are predictors of adverse clinical and PROs in patients with advanced NASH. (ClinicalTrials.gov, Numbers NCT01672866, NCT01672879, NCT03053050, and NCT03053063).
Authors: Jeffrey V Lazarus; Henry E Mark; Quentin M Anstee; Juan Pablo Arab; Rachel L Batterham; Laurent Castera; Helena Cortez-Pinto; Javier Crespo; Kenneth Cusi; M Ashworth Dirac; Sven Francque; Jacob George; Hannes Hagström; Terry T-K Huang; Mona H Ismail; Achim Kautz; Shiv Kumar Sarin; Rohit Loomba; Veronica Miller; Philip N Newsome; Michael Ninburg; Ponsiano Ocama; Vlad Ratziu; Mary Rinella; Diana Romero; Manuel Romero-Gómez; Jörn M Schattenberg; Emmanuel A Tsochatzis; Luca Valenti; Vincent Wai-Sun Wong; Yusuf Yilmaz; Zobair M Younossi; Shira Zelber-Sagi Journal: Nat Rev Gastroenterol Hepatol Date: 2021-10-27 Impact factor: 46.802
Authors: Zobair M Younossi; Maria Stepanova; Mazen Noureddin; Kris V Kowdley; Simone I Strasser; Anita Kohli; Peter Ruane; Mitchell L Shiffman; Aasim Sheikh; Nadege Gunn; Stephen H Caldwell; Ryan S Huss; Robert P Myers; Vincent Wai-Sun Wong; Naim Alkhouri; Zachary Goodman; Rohit Loomba Journal: Hepatol Commun Date: 2021-05-12