Effect of chelation therapy in pediatric Wilson’s disease: Liver and endoscopic outcome

Abstract

Background As there is paucity of exclusive literature on pediatric hepatic Wilson's disease (WD), this study was undertaken to evaluate the efficacy of chelation on hepatocellular function and portal hypertension in WD. Methods Wilson's disease patients with ≥9 months of follow‐up were evaluated for response to chelation therapy in the following categories: (a) complete remission, (b) partial remission (c) progression of disease; (d) drug toxicity. Pediatric end‐stage liver disease (PELD), Nazar and New Wilson Index scores were compared. Hemodynamically stable patients underwent esophagogastroduodenoscopy (baseline and surveillance) and received prophylaxis (primary or secondary). Endoscopic outcome was assessed at follow‐up. Results Of the 111 WD children (aged 9 [3–15] years; PELD score 16 [−11 to 60]), 65 with follow‐up of 3.6 (0.8–12) years on chelation (83% D‐penicillamine monotherapy, 17% D‐penicillamine and zinc) were analyzed. 81% had severe disease at presentation. Favorable outcome (complete and or partial remission), progression of disease and drug toxicity were seen in 71%, 29% and 10.8%, respectively. Two‐thirds had esophageal varices which did not show progression. Large esophageal varices (16%) were effectively downgraded in 3 (2–6) therapeutic endoscopic sessions. Nazar score and PELD score at baseline were independent predictors of outcome with favorable correlation with each other (r = .864, P < .001). PELD cutoff 9.45 (AUC: 71%, sensitivity: 87%, specificity: 50%; P = .009) and Nazar score cut off 3.5 (AUC: 68%, sensitivity: 83%, specificity: 50%; P = .02) were associated with poor prognosis. Conclusions Despite severe liver disease, the majority of hepatic WD can be managed on D‐penicillamine monotherapy. PELD score and Nazar score effectively determine the outcome.

Wilson Disease in Children; Chelation Therapy or Liver Transplantation? A 10-Year Experience from Pakistan

“…Only 2 (5.88%) of them were started on trientine because of bone marrow suppression. To date, over a mean period of 10 years, none of the patients in the present study who underwent chelation therapy have required LT. Our results are supported by studies from neighboring countries like India, where chelation therapy with penicillamine has shown good results, even in patients with severe hepatic disease [ 19 ]. Another study from India reported the adjunctive role of zinc therapy in pediatric WD, with good outcomes [ 20 ].…”

Early Diagnosis of Wilson’s Disease in Children in Southern China by Using Common Parameters

“…Its fundamental purpose is to restore the function of ATP7B -mediated hepatic and bile duct excretion of copper ( Murillo et al, 2016 ), and it may be the most promising treatment in the future. The incidence of acute liver failure in WD has previously been reported to be 15–47% ( Das et al, 2021 ; Devarbhavi et al, 2014 ; Rukunuzzaman, 2015 ). Among the successful follow-up cases in this group, except for one case (3.3%) with liver failure, the liver function recovered well after the application of penicillamine, oral zinc preparations, B vitamins, and low-copper diet, etc.…”

Chelation therapy in liver diseases of childhood: Current status and response

“…Biochemical parameters like serum albumin, total bilirubin and prothrombin time normalizes by 6 mo but liver enzymes might take longer[ 12 ]. In the author’s experience it takes 9-12 mo for complete normalization of Liver function tests in majority of the cases[ 50 ]. In patients who have additional neurological involvement, neurological response is monitored by indices such as Global assessment scale (GAS)[ 51 ].…”

“…77% of children responded to DPA monotherapy even when the disease is severe at presentation and 50% responded when DPA and zinc combination was started. The overall response to oral chelation is 71%[ 50 ]. Hence, DPA should be the first line of therapy for any hepatic WD and zinc is added in those who failed to show optimal response with DPA in desperate circumstances with the hope of rapid synergistic chelation and quicker liver recuperation[ 50 ].…”

“…The overall response to oral chelation is 71%[ 50 ]. Hence, DPA should be the first line of therapy for any hepatic WD and zinc is added in those who failed to show optimal response with DPA in desperate circumstances with the hope of rapid synergistic chelation and quicker liver recuperation[ 50 ]. Though there are no comparative trials of dual or single chelation therapy, there are limited case series that have used DPA or trientine with zinc for WD presenting with ascites, coagulopathy and encephalopathy[ 59 - 61 ].…”