OBJECTIVES: Guidelines support using non-invasive diagnostics (NID) for fibrosis staging but little evidence exists on their use alone or in sequence in RWD where imaging, biomarkers, and biopsy results are missing. This study compares fibrosis stage determined by Fibrosis-4 (FIB-4) versus multiple NID (MNID) including FIB-4, aspartate aminotransferase to platelet ratio, and non-alcoholic fatty liver disease fibrosis score as available in an existing large RWD.

METHODS: The Veradigm Health Insights Electronic Health Record Database and linked Komodo administrative claims data was used to identify adults with NASH. The index date was the earliest NASH diagnosis recorded between 2016 and 2020 with at least 6 months of database activity and continuous enrollment pre- and post-encounter with valid NID results. Fibrosis stage was defined using FIB-4 (F0/1: FIB-4≤0.95, F2: 0.95<FIB-4≤2.67, F3: 2.67<FIB-4≤4.12, F4: FIB-4>4.12) and compared to MNID.

RESULTS: 6,743 patients met the study criteria (mean age 55.8, SD=13.3; 62.9% female). A smaller proportion of patients were defined as F0/1 by FIB-4 vs MNID (34.8% vs 49.9%), and a larger proportion as F2 (48.8% vs 25.4%). Both approaches showed higher age and comorbid burden with increasing fibrosis stage, and increased prevalence of NASH-related conditions. Mean Charlson Comorbidity Index scores were 1.5 and 1.7 for FIB-4 and MNID stage F0/1 compared to 3.8 for F4 (both approaches); likewise, mean age increased from 46.0 and 51.6 for stage F0/1 to 65.2 for F4.

CONCLUSIONS: FIB-4 and MNID yielded similar results for patients with F3/F4 but differed for defining F0/1 versus F2; Although clinical validation is needed, the impact of this difference should be accounted for in study design and interpretation, particularly as it pertains to therapies targeting patients with F0/1 versus F2. Establishing a consistent approach for fibrosis staging in existing RWD will enable more efficient future research on emerging NASH therapies.