ArticleThe American journal of gastroenterology2026
Diagnosing Wilson Disease in Acute Liver Failure: Comparison of Existing and Experimental Biomarkers.
Article in The American journal of gastroenterology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionIn acute liver failure due to Wilson disease (ALF-WD), early and correct diagnosis is critical. Readily available biochemical parameters, e.g., ALT:AST ratio provide acceptable diagnostic accuracy. Recently, accurate nonceruloplasmin bound copper (ANCC), reflecting bioavailable serum copper and relative-ANCC (RelANCC) were developed. We investigated the diagnostic use of ANCC and RelANCC, and the validity of current diagnostic markers in ALF-WD.
methodsSerum samples and data were collected through the US ALF Study Group registry. Etiologies included ALF-WD (n = 23), acetaminophen (n = 11), autoimmune (n = 10), drug induced liver injury (n = 13), HBV/HDV (n = 10), and other (n = 3). Standard clinical and biochemical parameters, serum copper (s-Cu), ANCC, and RelANCC were measured. Receiver operating characteristic analysis was performed.
resultsBoth ANCC (cut-off ≥483 μg/L) and s-Cu (≥1369 μg/L) provided excellent diagnostic information for ALF-WD (area under the receiver operating curve [AUROC] 0.94 and 0.89). Low ALP (≤45 U/L), and ALT (≤52 U/L) individually provided diagnostic information for ALF-WD (AUROC's > 0.89). Combining ALT with either s-Cu or ANCC further improved diagnostic accuracy, with the ANCC-ALT score being more accurate, AUROC 0.99, sensitivity 91% and specificity 100%. Adding ALP:total bilirubin ratio, AST:ALT ratio or serum zinc to ANCC did not improve accuracy. Median RelANCC was significantly higher in patients with WD (64%) than in non-WD ALF patients (22%) ( P = 0.0001). DISCUSSION: Standard biochemistry provides excellent diagnostic information for identifying WD in the setting of ALF. Combining ALT with specific copper measurements significantly improved diagnostic use, with ANCC outperforming s-Cu. RelANCC may also be useful for WD diagnosis. We suggest adding s-Cu to the clinical algorithm in ALF.
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