NIKEI: a new inexpensive and non-invasive scoring system to exclude advanced fibrosis in patients with NAFLD

Abstract

Aims: To develop, validate and compare a non-invasive fibrosis scoring system for non-alcoholic fatty liver disease (NAFLD) derived from routinely obtained clinical and biochemical parameters.

Methods: 267 consecutive patients with biopsy proven fatty liver or non-alcoholic steatohepatitis were randomly assigned to the estimation (2/3) or validation (1/3) group to develop a model for the prediction of advanced fibrosis. Univariate statistics were performed to compare patients with and without advanced fibrosis, and following a multivariate logistic regression analysis a new scoring system was constructed. This non-invasive Koeln-Essen-index (NIKEI) was validated and compared to the FIB-4 index by calculating the area under the receiver operating characteristic curve (AUC). We evaluated a stepwise combination of both scoring systems for the precise prediction of advanced fibrosis. To set in contrast, we additionally tested the diagnostic accuracy of the AST/ALT ratio, BARD score and the NAFLD fibrosis score in our cohort.

Results: Age, AST, AST/ALT ratio, and total bilirubin were identified as significant predictors of advanced fibrosis and used to construct the NIKEI with an AUC of 0.968 [0.937; 0.998] compared to 0.929 [0.869; 0.989] for the FIB-4 index. The absence of advanced fibrosis could be confirmed with excellent accuracy (99-100%). The positive predictive value of the FIB-4 index was higher (100% vs. 60%), however, the false negative rate was also high (33%). With a stepwise combination of both indices 82%-84% of biopsies would have been avoidable without a single misclassification. The AUROC for AST/ALT ratio, the NAFLD fibrosis score, and the BARD score were 0.81 (95% CI, 0.72-0.90), 0.96 (95% CI 0.92-0.99), and 0.67 (95% CI 0.55-0.78), respectively.

Conclusion: The NIKEI can reliably exclude advanced fibrosis in subjects with NAFLD. In combination with the FIB-4 index misclassification with inadequate clinical management can be avoided while the need for liver biopsies can be reduced.

Figure 1. ROC-curve analysis for the prediction of advanced fibrosis with NIKEI, FIB-4 index and NAFLD fibrosis score.

a) estimation group (n = 154 with complete data for calculating both indices); b) validation group (n = 86 with complete data for calculating both indices). c) NAFLD fibrosis score (n = 120).

Figure 2. Stepwise combination of FIB-4 index and NIKEI.

Algorithm for the prediction of advanced fibrosis in NAFLD patients (estimation group, n = 154 with complete data for calculating both indices). Algorithm starts with the calculation of the FIB4 index followed by calculating NIKEI only for patients with negative or indeterminate test results. Shaded rectangles: liver biopsies which could have been avoided.