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

  • Appenzeller-Herzog, Christian1
  • Mathes, Tim2
  • Heeres, Marlies L S3
  • Weiss, Karl Heinz4
  • Houwen, Roderick H J3
  • Ewald, Hannah1, 5
  • 1 University Medical Library, University of Basel, Basel, Switzerland. , (Switzerland)
  • 2 Institute for Research in Operative Medicine, Faculty of Health, School of Medicine, Witten/Herdecke University, Cologne, Germany. , (Germany)
  • 3 Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands. , (Netherlands)
  • 4 Department of Internal Medicine IV, Medical University of Heidelberg, Heidelberg, Germany. , (Germany)
  • 5 Basel Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland. , (Switzerland)
Published Article
Liver international : official journal of the International Association for the Study of the Liver
Publication Date
Nov 01, 2019
DOI: 10.1111/liv.14179
PMID: 31206982


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. 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. 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. 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. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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