TY - JOUR
T1 - The Association of Histologic and Noninvasive Tests With Adverse Clinical and Patient-Reported Outcomes in Patients With Advanced Fibrosis Due to Nonalcoholic Steatohepatitis
AU - Younossi, Zobair M.
AU - Anstee, Quentin M.
AU - Wai-Sun Wong, Vincent
AU - Trauner, Michael
AU - Lawitz, Eric J.
AU - Harrison, Stephen A.
AU - Camargo, Marianne
AU - Kersey, Kathryn
AU - Subramanian, G. Mani
AU - Myers, Robert P.
AU - Stepanova, Maria
N1 - Publisher Copyright:
© 2021 AGA Institute
PY - 2021/4
Y1 - 2021/4
N2 - 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,
AB - 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,
KW - Abdominal Symptoms
KW - Fatigue
KW - Fatty Liver Disease
KW - Physical Functioning
KW - Vitality
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U2 - 10.1053/j.gastro.2020.12.003
DO - 10.1053/j.gastro.2020.12.003
M3 - Article
C2 - 33307033
AN - SCOPUS:85103698177
SN - 0016-5085
VL - 160
SP - 1608-1619.e13
JO - Gastroenterology
JF - Gastroenterology
IS - 5
ER -