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. 2025 Jul 23.
doi: 10.14309/ajg.0000000000003654. Online ahead of print.

Diagnosing Wilson Disease in Acute Liver Failure: Comparison of Existing and Experimental Biomarkers

Thomas Damgaard Sandahl  1 , Chris F Harrington  2   3 , Frederik Teicher Kirk  1 , Geoffrey Carpenter  2   3 , Leisa Douglas  2   3 , Craig Mills  2   3 , Jody A Rule  4 , William M Lee  4 , Ayse Coskun  5 , Michael L Schilsky  6
Affiliations

Diagnosing Wilson Disease in Acute Liver Failure: Comparison of Existing and Experimental Biomarkers

Thomas Damgaard Sandahl et al. Am J Gastroenterol. .

Abstract

Introduction: In 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.

Methods: Serum 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.

Results: Both 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.

Keywords: accurate nonceruloplasmin copper; ceruloplasmin; diagnosis; rare disease; screening.

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References

    1. Sandahl TD, Laursen TL, Munk DE, et al. The prevalence of Wilson's disease: An update. Hepatology 2020;71(2):722–32.
    1. Ala A, Walker AP, Ashkan K, et al. Wilson's disease. Lancet 2007;369(9559):397–408.
    1. Czlonkowska A, Litwin T, Dusek P, et al. Wilson disease. Nat Rev Dis Primers 2018;4(1):21.
    1. Schilsky ML, Roberts EA, Bronstein JM, et al. A multidisciplinary approach to the diagnosis and management of Wilson disease: 2022 Practice Guidance on Wilson disease from the American Association for the Study of Liver Diseases. Hepatology. 2022. doi:10.1002/hep.32801. - DOI
    1. Ostapowicz G, Fontana RJ, Schiødt FV, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med 2002;137(12):947–54.

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