# Nutritional-inflammatory indices optimize the diagnostic performance of FIB-4 for advanced fibrosis/cirrhosis in patients with benign liver disease

## TL;DR

Adding nutritional-inflammatory indices to FIB-4 improves accuracy in diagnosing advanced liver fibrosis/cirrhosis in patients with benign liver disease.

## Contribution

Combining FIB-4 with nutritional-inflammatory indices significantly enhances diagnostic performance for liver fibrosis/cirrhosis.

## Key findings

- The platelet-to-albumin ratio (PAR) outperformed HALP in diagnosing advanced fibrosis/cirrhosis.
- Combining FIB-4 with PAR or PNI significantly improved specificity and overall accuracy.
- A parallel strategy (FIB-4 + PAR or PNI) offers balanced performance with high feasibility for clinical use.

## Abstract

To address the high false-positive rate of fibrosis-4 (FIB-4), we hypothesize that combining it with readily available nutritional-inflammatory indices can improve the diagnostic accuracy for advanced liver fibrosis/cirrhosis.

Diagnostic performance was sequentially evaluated: first, individual metrics and FIB-4 were compared via receiver operating characteristics (ROC) curve analysis; then, their incremental value was assessed using DeLong’s test, net reclassification improvement (NRI) and integrated discrimination improvement (IDI); finally, the clinical utility of four combined strategies was examined.

In discriminating advanced fibrosis/cirrhosis, the platelet-to-albumin ratio (PAR) showed a significantly higher area under the curve (AUC) of 0.698 than the haemoglobin, albumin, lymphocyte and platelet (HALP, AUC= 0.494; p < .001). Similarly, the prognostic nutritional index (PNI) also outperformed HALP in diagnostic performance (AUC = 0.658; p < .0001). Adding PAR or PNI to FIB-4 significantly improved diagnostic performance, as evidenced by Delong’s test, NRI and IDI. Specifically, the combination of FIB-4 and PAR improved specificity (88.5% vs 38.5%) and overall accuracy (63.7% vs 54.8%) compared to FIB-4 alone, while the FIB-4 and PNI combination achieved a specificity of 80.3%. The parallel strategy (FIB-4 + ‘PAR or PNI’) maintained a sensitivity of 61.9% and achieved the highest negative predictive value (65.2%). The serial strategy (FIB-4 + ‘PAR and PNI’) provided the highest specificity (95.1%) and positive predictive value (81.8%).

In scenarios prioritizing high sensitivity, FIB-4 alone is suitable. For high specificity, a sequential strategy (FIB-4 + ‘PAR and PNI’) is recommended. For balanced performance, a parallel strategy (FIB-4 + ‘PAR or PNI’) provides optimal feasibility.

In settings where high sensitivity is prioritized for screening, the FIB-4 index may be used alone to minimize the risk of missed diagnoses.

In settings where high specificity is the primary goal, a sequential strategy (FIB-4 + ‘PAR and PNI’) is recommended to reduce the false positive rate as much as possible.

For routine screening that requires balanced overall diagnostic performance, a parallel strategy (FIB-4 + ‘PAR or PNI’) demonstrates relatively even performance across metrics and offers good feasibility for clinical application.