Serum keratin 18‐M65 levels detect progressive forms of alcohol‐associated liver disease in early noncirrhotic stages

Abstract

AbstractBackground and AimsThe progression of alcohol‐associated liver disease (ALD) in its early precirrhotic stages can be a silent process. Serum keratin 18 levels (K18‐M65) predict severe events and mortality in advanced stages of ALD, but data on this biomarker in early stages are scarce. We evaluated the diagnostic accuracy of K18‐M65 levels in identifying early forms of ALD.MethodsWe prospectively evaluated two cohorts of actively drinking patients with alcohol use disorder (AUD) following a rehabilitation program (training (n = 162) and validation (n = 78)) and matched healthy controls (n = 21). Clinical, laboratory, and imaging data were used to distinguish AUD patients with simple steatosis (minimal ALD) and steatohepatitis/fibrosis (early ALD). We measured serum K18‐M65 levels and assessed their ability to predict early ALD.ResultsHigh levels of K18‐M65 characterized AUD patients with early ALD, while levels in the minimal ALD group were similar to those in healthy controls. K18‐M65 levels distinguished minimal liver disease from early ALD (AUROC = 0.8704; p < 0.0001) with an optimal cutoff at 265.9 U/L. K18‐M65 levels strongly correlated with transaminases and predicted early ALD (OR 25.81; 95% CI 3.166–336.1; p < 0.0001), controlled attenuation parameter, and liver stiffness independently from transaminases and other potential confounders. K18‐M65 levels did not discriminate between fibrosis and steatohepatitis but correlated with histological signs of hepatocellular injury and inflammation (all p < 0.05). The K18‐M65 cutoff detected early ALD in the validation cohort with high accuracy (sensitivity 86.67%, specificity 96.67%) and a very high positive likelihood ratio (28.6; 95% CI 4.14–197.73).ConclusionsSerum K18‐M65 levels can be used as a biomarker to detect early ALD stages with excellent predictive value.