Adequate Chelation and Cupriuresis in Hepatic Wilson disease patients under Combination (Chelator + Zinc) therapy at 2 years of follow up

Abstract

Purpose Role of 24-hour urinary copper excretion (UCE) in treatment monitoring of Wilson disease (WD) is not well studied especially in pediatric population. Hence, present study is conducted with aim to evaluate UCE and its role in deciding therapeutic adequacy in paediatric WD on long-term follow-up. Methods All WD patients < 18 years and on combination therapy with atleast one UCE available after first year of treatment were included. Liver biochemistries, UCE (mcg/day) and serum non-ceruloplasmin bound copper (NCC) (mcg/dl) were assessed at diagnosis and various follow-ups. For assessment of treatment efficacy, criteria for adequate chelation (CAC) was defined as fulfilment of both (i) AST & ALT ≤ 1.5 times upper limit of normal, serum albumin > 3.5 gm/dl, INR < 1.5 and (ii) UCE < 500. Results Of the 74 included children, 70 (94.5%), 45 (60.8%), 28 (37.8%) and 21 (28.3%) completed 2-, 3-, 5- and 7- years follow-up respectively. Liver biochemistries improved significantly within 1 year of treatment. UCE decreased significantly from baseline of 654.08 ± 803.78 to 308.23 ± 175.93 at 2 years with no further change at 3 & 5 years follow-up. UCE at 2 years was < 200 in 28.5%, 200–500 in 55.7%, and > 500 in 15.7%. 61% achieved CAC by 2 years. On multivariate cox regression, treatment compliance was predictor for CAC achievement (p = 0.009, HR: 3.48, 95% CI: 1.36–8.86). Conclusion UCE declines significantly from baseline to < 500 mcg/day within 2 years. Majority of treatment compliant patients achieve CAC within 2 years of combination therapy.