Evaluation of Albumin Platelet Product for Fibrosis Detection in MASLD

A retrospective cohort study of 570 patients with either metabolic dysfunction-associated steatotic liver disease (MASLD) or metabolic dysfunction-associated steatohepatitis (MASH) has found that a novel blood-based biomarker, albumin platelet product (APP), performs comparably to Fibrosis-4 (FIB-4) overall and outperforms FIB-4 for cirrhosis detection in patients with diabetes.

The findings, published in the Canadian Liver Journal, suggest that current fibrosis screening tools may need to be adjusted for patients with diabetes, as diagnostic accuracy is reduced in this population.¹

The study was conducted at the Queen Elizabeth II Health Sciences Centre in Halifax, Nova Scotia, and included patients followed between January 2010 and August 2023. Investigators evaluated 4 noninvasive fibrosis indices, including APP, FIB-4, AST-to-platelet ratio index (APRI), and aspartate aminotransferase-alanine aminotransferase (AST/ALT) ratio. Clinical fibrosis staging was confirmed through liver biopsy, transient elastography (FibroScan), magnetic resonance elastography, or a combination of modalities.

Cirrhosis was highly prevalent in the cohort, confirmed in 56.4% of patients. Diabetes was present in 38% overall and increased progressively with fibrosis severity, from 24% in patients with no fibrosis (F0) to 46% in patients with cirrhosis (F4) (P < .001). When examining the entire study population, APP and FIB-4 showed similar effectiveness in identifying cirrhosis, achieving areas under the curve (AUC) of 0.85 and 0.84, respectively. Both markers substantially exceeded the performance of APRI and AST/ALT ratio, which each recorded AUCs of 0.76. For patients presenting with advanced fibrosis (stages F3-F4), FIB-4 had an AUC of 0.85, while APP had an AUC of 0.83. All 4 indices performed significantly better in patients without diabetes than in those with diabetes.

In patients with diabetes, APP showed better accuracy than FIB-4 for identifying cirrhosis, achieving an AUC of 0.80 versus 0.76 for FIB-4 (P = .04), while in evaluating advanced fibrosis, both markers performed comparably, with APP reaching an AUC of 0.81 and FIB-4 achieving 0.79 (P = .45). In contrast, among patients without diabetes, both APP and FIB-4 indices performed similarly for detecting both cirrhosis and advanced fibrosis.

The investigators also evaluated the performance of widely used FIB-4 thresholds in patients with diabetes versus those without. Using the conventional rule-out threshold of 1.3 and rule-in threshold of 2.67, test performance was consistently lower in individuals with diabetes. For cirrhosis detection, the 1.3 threshold yielded a sensitivity of 89% and a negative predictive value of only 59% in patients with diabetes, compared with 96% sensitivity and 93% negative predictive value in those without diabetes. For advanced fibrosis, the same 1.3 threshold provided 88% sensitivity but only 45% negative predictive value in the diabetic subgroup.

Based on these findings, the investigators “propose for the DM cohort an adjusted lower rule-out threshold of 1.22 and a higher rule-in threshold of 3.16 than published to achieve a 90% sensitivity and 90% specificity, respectively.” Because APP is less affected by diabetes status, they proposed unified thresholds of 8.25 and 9.27 to rule out cirrhosis and advanced fibrosis, achieving 90% sensitivity with negative predictive values ranging from 79% to 81%. “Our study has therefore not only validated the utility of the APP as a novel fibrosis index in the MASLD population but also derived new APP thresholds for detecting cirrhosis and advanced fibrosis in our patient population,” the authors report.

The findings support the continued use of FIB-4 for advanced fibrosis assessment in patients without diabetes, while positioning APP as a potentially more reliable alternative for fibrosis staging in patients with diabetes and MASLD.² The simplicity of APP calculation, which uses only serum albumin and platelet count without dependence on age or aminotransferase levels, is a practical advantage for routine clinical use.¹ The authors emphasize that revised, diabetes-specific thresholds for both FIB-4 and APP may be necessary to maintain diagnostic accuracy in this population.

MASLD can progress to MASH, cirrhosis, or liver cancer, particularly in individuals with type 2 diabetes mellitus and obesity. Nearly half of patients with cirrhosis in this cohort met criteria for diabetes, highlighting the need for systematic fibrosis screening in diabetic populations, particularly given the high burden of disease and the impracticality of liver biopsy for routine staging.

References

1. Lou A, Elnenaei M, Liu E, et al. Evaluation of a novel albumin platelet product (APP) fibrosis index and three non-invasive fibrosis indices in metabolic dysfunction-associated steatotic liver disease. Can Liver J. 2025;8(3):472-483. doi:10.3138/canlivj-2025-0017

2. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77(5):1797-1835. doi:10.1097/HEP.0000000000000323