Comparative effectiveness of common therapies for Wilson disease: A systematic review and meta-analysis of controlled studies

Liver Int. 2019 Nov;39(11):2136-2152. doi: 10.1111/liv.14179. Epub 2019 Jul 10.


Background & aims: Wilson disease (WD) is a rare disorder of copper metabolism. The objective of this systematic review was to determine the comparative effectiveness and safety of common treatments of WD.

Methods: We included WD patients of any age or stage and the study drugs D-penicillamine, zinc salts, trientine and tetrathiomolybdate. The control could be placebo, no treatment or any other treatment. We included prospective, retrospective, randomized and non-randomized studies. We searched Medline and Embase via Ovid, the Cochrane Central Register of Controlled Trials, and screened reference lists of included articles. Where possible, we applied random-effects meta-analyses.

Results: The 23 included studies reported on 2055 patients and mostly compared D-penicillamine to no treatment, zinc, trientine or succimer. One study compared tetrathiomolybdate and trientine. Post-decoppering maintenance therapy was addressed in one study only. Eleven of 23 studies were of low quality. When compared to no treatment, D-penicillamine was associated with a lower mortality (odds ratio 0.013; 95% CI 0.0010 to 0.17). When compared to zinc, there was no association with mortality (odds ratio 0.73; 95% CI 0.16 to 3.40) and prevention or amelioration of clinical symptoms (odds ratio 0.84; 95% CI 0.48 to 1.48). Conversely, D-penicillamine may have a greater impact on side effects and treatment discontinuations than zinc.

Conclusions: There are some indications that zinc is safer than D-penicillamine therapy while being similarly effective in preventing or reducing hepatic or neurological WD symptoms. Study quality was low warranting cautious interpretation of our findings.

Keywords: Wilson disease; hepatolenticular degeneration; meta-analysis; systematic review.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Chelating Agents / adverse effects*
  • Chelating Agents / therapeutic use*
  • Copper / metabolism
  • Hepatolenticular Degeneration / drug therapy*
  • Humans
  • Liver / metabolism
  • Molybdenum / adverse effects
  • Molybdenum / therapeutic use
  • Penicillamine / adverse effects
  • Penicillamine / therapeutic use
  • Randomized Controlled Trials as Topic
  • Trientine / adverse effects
  • Trientine / therapeutic use
  • Zinc / adverse effects
  • Zinc / therapeutic use*


  • Chelating Agents
  • Copper
  • Molybdenum
  • tetrathiomolybdate
  • Penicillamine
  • Zinc
  • Trientine