Validation of a two‐step approach combining serum biomarkers and liver stiffness measurement to predict advanced fibrosis

Abstract Background and Aim The Gut and Obesity in Asia Workgroup recently reported that a two‐step approach using fibrosis scores followed by liver stiffness measurement (LSM) could accurately detect patients with non‐alcoholic fatty liver disease (NAFLD) having advanced fibrosis in low‐risk fibrosis populations. This study aimed to validate the utility of this approach using a Japanese health checkup registry. Methods This cross‐sectional study included subjects who underwent a health checkup from 2014 to 2019. Using estimated fibrosis stage measured by LSM as a standard, we calculated the percentage of misclassification from assessments made based on fibrosis scores (NAFLD fibrosis score [NFS] or Fibrosis‐4 score [FIB‐4]) and LSM, alone or in combination. Results Of 630 subjects with NAFLD, 4 (0.8%) had advanced fibrosis. In the first‐step evaluation, only 21.4–38.0% of subjects needed further testing. This approach was associated with a high specificity of approximately 100% and a negative predictive value of 99.7%. The percentage of misclassification based on NFS or FIB‐4 values followed by LSM in all subjects and using LSM after NFS or FIB‐4 determination only in subjects with indeterminate/high NFS or FIB‐4 values (two‐step approach) was 0% and 0.3% and 0.16% and 0.3%, respectively. In addition, very few false negatives occurred for both NFS and FIB‐4. Conclusion The two‐step approach helps to identify the subjects with NAFLD who have advanced fibrosis during a routine health checkup and is associated with only a few false negatives