Fibrosis index nine superiority for cirrhosis in hypopituitarism: Clinical validation of endocrine liver triage tool

Abstract

BACKGROUND

Hypopituitarism is a high-risk factor for rapidly progressive metabolic dysfunction-associated steatotic liver disease (MASLD) and cirrhosis. Conventional non-invasive tests (NITs) like the fibrosis-4 (FIB-4) index often lack accuracy in endocrine-mediated contexts. The machine-learning-based fibrosis-9 (FIB-9) index shows promise in general MASLD but remains unvalidated in hypopituitarism. We hypothesized that FIB-9 would outperform traditional NITs in identifying cirrhosis among these clinical populations.

AIM

To evaluate FIB-9 performance and compare it with traditional indices and markers for cirrhosis in hypopituitarism.

METHODS

This retrospective study of 35 patients (19 cirrhosis, 16 non-cirrhosis) evaluated the diagnostic accuracy of the FIB-9 index. Comparisons were made with the FIB-4 index, aspartate aminotransferase-to-platelet ratio index (APRI), direct serum fibrosis markers [hyaluronic acid (HA), procollagen III N-terminal peptide, type IV collagen, and laminin], and liver stiffness measurement (LSM). Performance was assessed using the area under the receiver operating characteristic curve (AUROC) method.

RESULTS

FIB-9 was significantly higher in the cirrhosis group than in controls [3.75 (2.04, 3.99) vs 0.49 (0.04, 1.59), P < 0.001]. FIB-9 demonstrated the highest diagnostic accuracy (AUROC = 0.941; 95%CI: 0.856-1.000), outperforming APRI (AUROC = 0.903), FIB-4 (AUROC = 0.872), and direct markers like HA (AUROC = 0.878). At an optimal cutoff of 1.748, FIB-9 yielded 89.5% sensitivity and 100.0% specificity. Notably, individual parameters such as alanine aminotransferase (P = 0.417) and albumin (P = 0.109) failed to distinguish between groups. LSM was significantly elevated in the cirrhosis group [23.2 (15.8, 31.9) kPa vs 5.7 (3.9, 6.8) kPa, P < 0.001].

CONCLUSION

The FIB-9 index is superior to traditional indices and direct markers for identifying cirrhosis in hypopituitarism, serving as a highly reliable rule-in tool for clinical triage.

Keywords: Hypopituitarism; Liver fibrosis; Cirrhosis; Non-invasive test; Craniopharyngioma; Fibrosis-9 index; Fibrosis-4 index; Aspartate aminotransferase-to-platelet ratio index; Liver stiffness measurement; Metabolic dysfunction-associated steatotic liver disease

Core Tip: Patients with hypopituitarism are at high risk for rapidly progressive metabolic liver disease, yet traditional non-invasive tests often lack accuracy in this specific endocrine-mediated context. This study provides the first clinical validation of the fibrosis-9 (FIB-9) index in hypopituitary patients. Our findings reveal that FIB-9 (area under the receiver operating characteristic curve = 0.941) significantly outperforms aspartate aminotransferase-to-platelet ratio index, fibrosis-4, and conventional serum markers in identifying cirrhosis. Using an optimal cutoff of 1.748, FIB-9 serves as a highly reliable triage tool, enabling clinicians to accurately identify high-risk patients for advanced liver assessment while sparing others from unnecessary testing.