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The objective of this systematic review was to determine the comparative effectiveness and safety of common treatments of WD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We included WD patients of any age or stage and the study drugs D\u2010penicillamine, zinc salts, trientine and tetrathiomolybdate. The control could be placebo, no treatment or any other treatment. We included prospective, retrospective, randomized and non\u2010randomized 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\u2010effects meta\u2010analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The 23 included studies reported on 2055 patients and mostly compared D\u2010penicillamine to no treatment, zinc, trientine or succimer. One study compared tetrathiomolybdate and trientine. Post\u2010decoppering maintenance therapy was addressed in one study only. Eleven of 23 studies were of low quality. When compared to no treatment, D\u2010penicillamine 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\u2010penicillamine may have a greater impact on side effects and treatment discontinuations than zinc.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>There are some indications that zinc is safer than D\u2010penicillamine therapy while being similarly effective in preventing or reducing hepatic or neurological WD symptoms. Study quality was low warranting cautious interpretation of our findings.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14179","type":"journal-article","created":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T17:17:31Z","timestamp":1560791851000},"page":"2136-2152","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Comparative effectiveness of common therapies for Wilson disease: A systematic review and meta\u2010analysis of controlled studies"],"prefix":"10.1111","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7430-294X","authenticated-orcid":false,"given":"Christian","family":"Appenzeller\u2010Herzog","sequence":"first","affiliation":[{"name":"University Medical Library, University of Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Mathes","sequence":"additional","affiliation":[{"name":"Institute for Research in Operative Medicine, Faculty of Health, School of Medicine Witten\/Herdecke University Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlies L.S.","family":"Heeres","sequence":"additional","affiliation":[{"name":"Wilhelmina Children's Hospital University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl Heinz","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV Medical University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick H.J.","family":"Houwen","sequence":"additional","affiliation":[{"name":"Wilhelmina Children's Hospital University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5081-1093","authenticated-orcid":false,"given":"Hannah","family":"Ewald","sequence":"additional","affiliation":[{"name":"University Medical Library, University of Basel Basel Switzerland"},{"name":"Basel Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research University Hospital Basel and University of Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,10]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60196-2"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/34.4.295"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1293-327"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-63625-6.00009-4"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-63625-6.00010-0"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(56)90066-3"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(82)92201-2"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000115077"},{"key":"e_1_2_11_10_1","unstructured":"SchouwinkG.De hepato\u2010cerebrale degeneratie: met een onderzoek van de zinkstofwisseling. 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