Liver Iron Accumulation in Recompensated Wilson Disease on Chelation Therapy: A Prospective Evaluation in Children

螯合治疗对代偿期威尔逊氏病患儿肝脏铁沉积的影响:一项前瞻性研究

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Abstract

BACKGROUND: As serum ceruloplasmin has ferroxidase properties, we hypothesized that Wilson disease (WD) may have greater iron accumulation than other liver diseases. We aimed to assess liver iron overload in WD by evaluating the iron metabolism biomarkers and liver iron concentration (LIC). METHODS: Compensated and recompensated WD patients with ≥3 years of chelation and serum exchangeable copper (ExCu) < 1.15 μmol/L were recruited and compared to controls. All patients underwent assessment of iron metabolism biomarkers and T2∗-weighted liver magnetic resonance imaging (MRI) for LIC. High LIC was defined as >1.5 mg/g dry weight (dw). RESULTS: Thirty-seven WD patients were compared to age, sex, and liver disease score-matched controls (n = 10). High LIC was seen in 49% WD vs. 10% controls (P = 0.027). In those with a duration of chelation ≥6 years vs. <6 years, high LIC was found in 89% vs. 58% (P = 0.03). High LIC was seen in 3/9 (30%), 7/15 (47%), and 8/13 (62%) of the WD patients in 3-5 years, 6-9 years, and 10-12 years of chelation therapy, respectively. In those with LIC >1.5 mg/g dw (n = 18) and LIC >2.0 mg/g dw (n = 10), longer duration of chelation therapy inversely correlated with serum ferroxidase activity (r = -0.7, P < 0.001; r = -0.75, P = 0.01 respectively). Serum ferritin had poor correlation with LIC (r = 0.177, P = 0.3). Mean (standard deviation) ExCu in high vs. normal LIC were 0.66 (0.27) vs. 0.94 (0.33), P = 0.01. CONCLUSION: High LIC is found in approximately half of WD patients, especially in those with ≥6 years of chelation therapy and low ExCu. MRI is recommended as a screening tool for iron overload in WD.

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