Clinical Utility of Metallothionein Immunohistochemistry (MT-IHC) for Early Tissue-based Diagnosis of Wilson Disease (WD)

Wilson Disease (WD) is an inherited disorder resulting from ATP7B gene mutations, causing toxic copper accumulation in the liver and central nervous system. Traditionally, WD diagnosis in symptomatic patients relies on blood, urine, and genetic testing; however, patients with isolated liver enzyme elevations may remain undiagnosed, risking progression to cirrhosis. Recently, Metallothionein immunohistochemistry (MT-IHC) has shown robust diagnostic performance for tissue-based WD diagnosis (Stokes et al., 2024; Wiethoff et al., 2023). To explore its clinical utility, we analyzed the test results of MT-IHC one year after integration into the routine workup of liver biopsies at the Institute of Pathology, University Hospital Heidelberg. Over 20 months, 154 liver specimens (147 biopsies, 7 explants) were stained for MT, where WD was a differential diagnosis based on clinical or histological findings (median age: 44 years, IQR: 30–61.25; 62% male). 16 biopsies stained positive for MT; 11 of these exhibited advanced fibrosis or cirrhosis (Stage 3-4). WD was confirmed clinically and genetically in 5 cases and remained a relevant differential in 9 cases, with available follow-up data for 1 case harboring a relevant ATP7B gene mutation. Notably, MT-IHC established WD diagnosis in 2 asymptomatic cases, including 1 case, where the diagnosis was determined only after liver transplantation, highlighting the clinical value of MT-IHC as a screening tool in any liver biopsy, where WD is a potential differential. Our findings support the clinical utility of MT-IHC for early WD diagnosis in liver biopsy specimens, emphasizing its role in improving outcomes through timely intervention.

Publication History

Article published online:
20 January 2025