Validation of the FIB4 index in a Japanese nonalcoholic fatty liver disease population

BMC Gastroenterol. 2012 Jan 5;12:2. doi: 10.1186/1471-230X-12-2.


Background: A reliable and inexpensive noninvasive marker of hepatic fibrosis is required in patients with nonalcoholic fatty liver disease (NAFLD). FIB4 index (based on age, aspartate aminotransferase [AST] and alanine aminotransferase [ALT] levels, and platelet counts) is expected to be useful for evaluating hepatic fibrosis. We validated the performance of FIB4 index in a Japanese cohort with NAFLD.

Methods: The areas under the receiver operating characteristic curves (AUROC) for FIB4 and six other markers were compared, based on data from 576 biopsy-proven NAFLD patients. Advanced fibrosis was defined as stage 3-4 fibrosis. FIB4 index was assessed as: age (yr) × AST (IU/L)/(platelet count (10(9)/L) × √ALT (IU/L)) RESULTS: Advanced fibrosis was found in 64 (11%) patients. The AUROC for FIB4 index was superior to those for the other scoring systems for differentiating between advanced and mild fibrosis. Only 6 of 308 patients with a FIB4 index below the proposed low cut-off point (< 1.45) were under-staged, giving a high negative predictive value of 98%. Twenty-eight of 59 patients with a FIB4 index above the high cut-off point (> 3.25) were over-staged, giving a low positive predictive value of 53%. Using these cutoffs, 91% of the 395 patients with FIB-4 values outside 1.45-3.25 would be correctly classified. Implementation of the FIB4 index in the Japanese population would avoid 58% of liver biopsies.

Conclusion: The FIB4 index was superior to other tested noninvasive markers of fibrosis in Japanese patients with NAFLD, with a high negative predictive value for excluding advanced fibrosis. The small number of cases of advanced fibrosis in this cohort meant that this study had limited power for validating the high cut-off point.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Alanine Transaminase / blood*
  • Aspartate Aminotransferases / blood*
  • Biomarkers
  • Biopsy
  • Cohort Studies
  • Fatty Liver / blood*
  • Fatty Liver / diagnosis
  • Fatty Liver / ethnology*
  • Female
  • Humans
  • Japan
  • Liver / pathology
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / ethnology
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease
  • Platelet Count*
  • Predictive Value of Tests
  • ROC Curve
  • Retrospective Studies
  • Severity of Illness Index*


  • Biomarkers
  • Aspartate Aminotransferases
  • Alanine Transaminase