title: Zinc monotherapy is effective in Wilson's disease patients with mild liver disease diagnosed in childhood: a retrospective study.
abstract: BACKGROUND
  Wilson's disease (WD) evolves rapidly and is fatal if untreated. The treatment of WD patients with mild liver disease is not clearly defined. To address this issue, we evaluated long-term outcomes of three treatment regimens (D-penicillamine, zinc or both) in patients diagnosed in childhood.
  
  
  METHODS
  We retrospectively evaluated efficacy, compliance and reasons for treatment discontinuation in 42 WD patients (median age at diagnosis: 6 years; median follow-up: 12 years) with mild liver disease. Treatment duration for each treatment block until a medication change or completion of follow-up was analyzed. Events of change of treatment were evaluated using Kaplan-Meier analysis.
  
  
  RESULTS
  Total discontinuations due to treatment failure or adverse events were more frequent in patients receiving D-penicillamine (45%) or combination (36%) therapy than in patients receiving zinc (12%) (P = .001 and P = .02, respectively). Treatment failure was more frequent on D-penicillamine (28%) and combination therapy (36%) than on zinc (12%); the difference was statistically significant only between zinc and combination therapy (P = .03). First-line zinc monotherapy controlled WD-related liver disease in 13/15 patients (87%); the two subjects that failed on zinc were poor adherent. Zinc was effective in 3/5 (60%) patients that failed on D-penicillamine and combination regimens. All 15 D-penicillamine responders that switched to zinc had good control of liver disease at a median follow-up of 13.1 years. Among 6 D-penicillamine non-responders that switched to zinc, 4 (67%) responded. At follow-up completion, only 5/42 (12%) patients failed. Adverse event-induced discontinuation was significantly more frequent in patients on D-penicillamine than in patients receiving zinc (P = .03).
  
  
  CONCLUSIONS
  Zinc monotherapy is effective in controlling WD-related liver disease both as first-line and as maintenance treatment in patients with mild liver disease diagnosed in childhood.
authors.forename: Giusy
authors.initials: G
authors.lastname: Ranucci
authors.forename: Fabiola
authors.initials: F
authors.lastname: Di Dato
authors.forename: Maria Immacolata
authors.initials: MI
authors.lastname: Spagnuolo
authors.forename: Pietro
authors.initials: P
authors.lastname: Vajro
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Via Pansini 5, 80131 Naples, Italy. riorio@unina.it.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Iorio
mesh_terms: D000251:Adenosine Triphosphatases; D027682:Cation Transport Proteins; D000073840:Copper-Transporting ATPases; D005260:Female; D006527:Hepatolenticular Degeneration / Q000188:drug therapy*; D006801:Humans; D008107:Liver Diseases / Q000188:drug therapy*; D008297:Male; D012189:Retrospective Studies; D015032:Zinc / Q000627:therapeutic use*
chemical_list: D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases; D015032:Zinc