Alkaline phosphatase refines FIB-4-based prediction of liver outcomes and mortality in MASLD
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Published on: November 27, 2019
Or Shimoni1, Emma Hajaj1, Shiri Kushnir2
1Department of Medicine D, Rabin Medical Center, Beilinson Campus, Petah-Tikva, Israel.
Background:
FIB-4 is recommended for first-line MASLD risk stratification but excludes cholestatic liver enzymes.
Aims:
To assess whether alkaline phosphatase (ALK) improves prediction of major adverse liver outcomes (MALO) and mortality beyond FIB-4.
Methods:
In this retrospective cohort study (2004-2025), adults aged ≥35 years with MASLD or type 2 diabetes with BMI >27 kg/m² were classified by baseline ALK ≥120 U/L and age-adjusted FIB-4 strata. Cause-specific Cox models assessed 10-year MALO and mortality.
Results:
Among 388,933 participants (mean age 59 years; 53% female), 35,073 (9%) had elevated ALK. Ten-year MALO incidence was higher with elevated ALK across low (1.5%vs 1.1%), intermediate (2.8%vs 1.6%), and high FIB-4 strata (11.9%vs 4.5%). Compared with low FIB-4 and normal ALK, adjusted hazard ratios for MALO were 1.41 (95% CI 1.25-1.59), 2.58 (2.17-3.07), and 9.57 (8.06-11.3) for low, intermediate, and high FIB-4 with elevated ALK, respectively. FIB-4 and ALK were independently associated with MALO, with significant interaction (P < 0.001) and improved event reclassification. Findings were consistent after incorporating GGT.
Conclusions:
Elevated ALK identifies MASLD patients at higher liver-related risk and modifies FIB-4-associated risk. Incorporating cholestatic enzyme status into FIB-4-based assessment may improve non-invasive triage and referral decisions.
