Aims: Wilson disease (WD) is a genetic disorder of copper metabolism caused by mutations
in the ATP7B gene. Toxic copper accumulation leads to hepatic, neurologic, and psychiatric
disorders with variable presentation. Metallothionein (MT) immunohistochemistry was
proposed as a diagnostic marker.
Methods: MT immunohistochemistry was performed on liver specimens of WD patients (n=64) and
control cases (n=160) including acute liver failure, steatotic liver disease, autoimmune
hepatitis, normal liver, primary biliary cholangitis, primary and secondary sclerosing
cholangitis, and progressive familial intrahepatic cholestasis. The optimal cutoff
for detection of WD was determined by receiver operating characteristic (ROC) analysis.
Results: At least moderate staining in>50% of hepatocytes was observed in 81% of analysed
liver specimens (n=56/69) of WD patients, while only five control cases showed this
staining pattern. The sensitivity, specificity, and accuracy for a new diagnosis of
WD were 85.7%, 96.9%, and 94.9%, respectively. Sensitivity in nonfibrotic patients
was 70.6% and this MT pattern was robust in small biopsies. The hepatic copper concentration
was similar between MT-positive and MT-negative liver samples (P>0.05). Zinc treatment
may induce hepatocellular MT expression. Kayser-Fleischer rings (50% versus 15%) and
neurologic disorders (50% versus 13%) were significantly more prevalent in MT-negative
compared to MT-positive WD patients, respectively.
Conclusion: MT immunostaining is an excellent biomarker for histological diagnosis of WD, should
be incorporated in the diagnostic work-up of patients with potential WD, and is useful
in a modified Leipzig score.
Informationen zum Einsatz von KI: Keine Verwendung von KI.
