Limitations of Noninvasive Tests-Based Population-Level Risk Stratification Strategy for Nonalcoholic Fatty Liver Disease

Jaideep Behari, Allison Bradley, Kevin Townsend, Michael J. Becich, Nickie Cappella, Cynthia H. Chuang, Soledad A. Fernandez, Daniel E. Ford, H. Lester Kirchner, Richard Morgan, Anuradha Paranjape, Jonathan C. Silverstein, David A. Williams, W. Troy Donahoo, Sumeet K. Asrani, Fady Ntanios, Mohammad Ateya, Rozelle Hegeman-Dingle, Euan McLeod, Kathleen McTigue

Research output: Contribution to journalArticlepeer-review


Background: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are highly prevalent but underdiagnosed. Aims: We used an electronic health record data network to test a population-level risk stratification strategy using noninvasive tests (NITs) of liver fibrosis. Methods: Data were obtained from PCORnet® sites in the East, Midwest, Southwest, and Southeast United States from patients aged ≥ 18 with or without ICD-10-CM diagnosis codes for NAFLD, NASH, and NASH-cirrhosis between 9/1/2017 and 8/31/2020. Average and standard deviations (SD) for Fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), and Hepatic Steatosis Index (HSI) were estimated by site for each patient cohort. Sample-wide estimates were calculated as weighted averages across study sites. Results: Of 11,875,959 patients, 0.8% and 0.1% were coded with NAFLD and NASH, respectively. NAFLD diagnosis rates in White, Black, and Hispanic patients were 0.93%, 0.50%, and 1.25%, respectively, and for NASH 0.19%, 0.04%, and 0.16%, respectively. Among undiagnosed patients, insufficient EHR data for estimating NITs ranged from 68% (FIB-4) to 76% (NFS). Predicted prevalence of NAFLD by HSI was 60%, with estimated prevalence of advanced fibrosis of 13% by NFS and 7% by FIB-4. Approximately, 15% and 23% of patients were classified in the intermediate range by FIB-4 and NFS, respectively. Among NAFLD-cirrhosis patients, a third had FIB-4 scores in the low or intermediate range. Conclusions: We identified several potential barriers to a population-level NIT-based screening strategy. HSI-based NAFLD screening appears unrealistic. Further research is needed to define merits of NFS- versus FIB-4-based strategies, which may identify different high-risk groups.

Original languageEnglish (US)
Pages (from-to)370-383
Number of pages14
JournalDigestive Diseases and Sciences
Issue number2
StatePublished - Feb 2024

All Science Journal Classification (ASJC) codes

  • Physiology
  • Gastroenterology

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