Sustained Elevation in Alkaline Phosphatase is Associated with Greater Disease Severity in Real World NAFLD in TARGET-NASH.

Challenge

Sustained alkaline phosphatase elevation in NAFLD is recognized as a marker of cholestatic injury and advanced disease, but its independent association with disease severity outcomes in a large real-world cohort had not been established, limiting its utility as a monitoring biomarker.

Solution

The TARGET-NASH cohort was analyzed to compare clinical characteristics and outcomes between patients with sustained ALP elevation (≥2 consecutive values >1.5x ULN) versus non-elevated ALP, stratified by disease severity, characterizing the association between sustained ALP elevation and decompensation events.

Impact

Establishing that sustained ALP elevation is independently associated with higher MELD scores and decompensation events in NAFLD cirrhosis provides evidence for ALP as a monitoring biomarker and supports its inclusion in composite safety and outcome endpoints in advanced NAFLD studies.