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Abstract Details
Improvements of Fibrosis and Disease Activity Are Associated With Improvement of Patient-Reported Outcomes in Patients With Advanced Fibrosis Due to Nonalcoholic Steatohepatitis
Hepatol Commun. 2021 May 12;5(7):1201-1211. doi: 10.1002/hep4.1710. eCollection 2021 Jul.
Zobair M Younossi12, Maria Stepanova3, Mazen Noureddin4, Kris V Kowdley5, Simone I Strasser6, Anita Kohli7, Peter Ruane8, Mitchell L Shiffman9, Aasim Sheikh10, Nadege Gunn11, Stephen H Caldwell12, Ryan S Huss13, Robert P Myers13, Vincent Wai-Sun Wong14, Naim Alkhouri15, Zachary Goodman12, Rohit Loomba4
Author information
1Betty and Guy Beatty Center for Integrated Research Inova Health System Falls Church VA USA.
2Department of Medicine Center for Liver Diseases Inova Fairfax Hospital Falls Church VA USA.
3Center for Outcomes Research in Liver Disease Washington DC USA.
4NAFLD Research Center University of California at San Diego La Jolla CA USA.
5Liver Institute Northwest Seattle WA USA.
6Royal Prince Alfred Hospital University of Sydney Sydney Australia.
7Arizona Liver Health Chandler AZ USA.
8Ruane Medical and Liver Health Institute Los Angeles CA USA.
9Liver Institute of Virginia Bon Secours Mercy Health Richmond VA USA.
10GI Specialists of Georgia Marietta GA USA.
11Pinnacle Clinical Research Austin TX USA.
12University of Virginia Charlottesville VA USA.
13Gilead Sciences, Inc. Foster City CA USA.
14Department of Medicine and Therapeutics The Chinese University of Hong Kong Hong Kong China.
15Texas Liver Institute UT Health San Antonio San Antonio TX USA.
Abstract
Patient-reported outcomes (PROs) are important endpoints for clinical trials. The impact of investigational drugs on PROs of patients with advanced nonalcoholic steatohepatitis (NASH) was investigated. Patients with NASH with bridging fibrosis or compensated cirrhosis were enrolled in a phase 2, randomized, placebo-controlled study of selonsertib, firsocostat, or cilofexor, alone or in two-drug combinations (NCT03449446). PROs included Short Form 36 (SF-36), Chronic Liver Disease Questionnaire (CLDQ)-NASH, EuroQol Five Dimension (EQ-5D), Work Productivity and Impairment (WPAI), and 5-D Itch before and during treatment. A total of 392 patients with NASH (mean ± SD, 60 ± 9 years old; 35% men; 89% white; 72% diabetes; and 56% compensated cirrhosis) were included. Baseline Physical Functioning (PF) and Bodily Pain of SF-36 and Fatigue and Worry of CLDQ-NASH were significantly lower in patients with cirrhosis (total CLDQ-NASH score mean ± SD, 4.91 ± 1.06 with cirrhosis vs. 5.16 ± 1.14 without cirrhosis; P < 0.05). Lower baseline PRO scores were independently associated with age, female sex, greater body mass index, diabetes, clinically overt fatigue, and comorbidities (all P < 0.05). After 48 weeks of treatment, patients with ≥1-stage fibrosis improvement without worsening of NASH experienced improvement in EQ-5D and five out of six CLDQ-NASH domains (P < 0.05). Patients with ≥2-point decrease in their nonalcoholic fatty liver disease activity score (NAS) also had improvements in PF and Role Physical scores and all domains of CLDQ-NASH (P < 0.05). Progression to cirrhosis was associated with a decrease in PF scores of SF-36 (P ≤ 0.05). Fibrosis regression was independently associated with greater improvements in PF and EQ-5D scores, while NAS improvement was associated with improvement in fatigue and pruritus (all P < 0.05). Conclusion: Patients with advanced NASH experienced improvement in their PROs after fibrosis regression or improvement in disease activity.