Advanced liver fibrosis and the metabolic syndrome in a primary care setting

Diabetes Metab Res Rev. 2021 Nov;37(8):e3452. doi: 10.1002/dmrr.3452. Epub 2021 Apr 9.


Aims: The fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) are noninvasive and accessible methods for assessing advanced liver fibrosis risk in primary care. We evaluated the distribution of FIB-4 and NFS scores in primary care patients with clinical signals for nonalcoholic fatty liver disease (NAFLD).

Materials and methods: This retrospective cohort study of electronic record data between 2007 and 2018 included adults with at least one abnormal aminotransferase and no known (non-NAFLD) liver disease. We calculated patient-level FIB-4 and NFS scores, the proportion of patients with mean values exceeding advanced fibrosis thresholds (indeterminate risk: FIB-4 > 1.3, NFS > -1.455; high-risk: FIB-4 > 2.67, NFS > 0.676), and the proportion of patients with a NAFLD International Classification of Diseases-9/10 code. Logistic regression models evaluated the associations of metabolic syndrome (MetS) components with elevated FIB-4 and NFS scores.

Results: The cohort included 6506 patients with a median of 6 (interquartile range: 3-13) FIB-4 and NFS scores per patient. Of these patients, 81% had at least two components of MetS, 29% had mean FIB-4 and NFS scores for indeterminate fibrosis risk, and 11% had either mean FIB-4 or NFS scores exceeding the high advanced fibrosis risk thresholds. Regression models identified associations of low high-density lipoprotein, hyperglycemia, Black race and male gender with high-risk FIB-4 and NFS values. Only 5% of patients had existing diagnoses for NAFLD identified.

Conclusions: Many primary care patients have FIB-4 and NFS scores concerning for advanced fibrosis, but rarely a diagnosis of NAFLD. Elevated FIB-4 and NFS scores may provide signals for further clinical evaluation of liver disease in primary care settings.

Keywords: FIB-4; NFS; cirrhosis; fibrosis; hepatology; nonalcoholic fatty liver disease; noninvasive testing.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alanine Transaminase
  • Aspartate Aminotransferases
  • Biopsy
  • Humans
  • Liver
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / epidemiology
  • Male
  • Metabolic Syndrome* / complications
  • Metabolic Syndrome* / diagnosis
  • Metabolic Syndrome* / epidemiology
  • Non-alcoholic Fatty Liver Disease* / complications
  • Non-alcoholic Fatty Liver Disease* / diagnosis
  • Non-alcoholic Fatty Liver Disease* / epidemiology
  • Primary Health Care
  • Retrospective Studies
  • Severity of Illness Index


  • Aspartate Aminotransferases
  • Alanine Transaminase