Differences in the Time Course of Recovery from Brain and Liver Dysfunction in Conventional Long-Term Treatment of Wilson Disease
Background: The aim of this study was to demonstrate that both neurological and hepatic symptoms respond to copper chelation therapy in Wilson disease (WD). However, the time course of their recovery is different. Methods: Eighteen patients with neurological WD from a single specialized center who h...
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MDPI AG
2023-07-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/12/14/4861 |
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| author | Harald Hefter Theodor S. Kruschel Max Novak Dietmar Rosenthal Tom Luedde Sven G. Meuth Philipp Albrecht Christian J. Hartmann Sara Samadzadeh |
| author_facet | Harald Hefter Theodor S. Kruschel Max Novak Dietmar Rosenthal Tom Luedde Sven G. Meuth Philipp Albrecht Christian J. Hartmann Sara Samadzadeh |
| author_sort | Harald Hefter |
| collection | DOAJ |
| description | Background: The aim of this study was to demonstrate that both neurological and hepatic symptoms respond to copper chelation therapy in Wilson disease (WD). However, the time course of their recovery is different. Methods: Eighteen patients with neurological WD from a single specialized center who had been listed for liver transplantation during the last ten years and two newly diagnosed homozygous twins were recruited for this retrospective study. The mean duration of conventional treatment was 7.3 years (range: 0.25 to 36.2 years). A custom Wilson disease score with seven motor items, three non-motor items, and 33 biochemical parameters of the blood and urine, as well as the MELD score, was determined at various checkup visits during treatment. These data were extracted from the charts of the patients. Results: Treatment was initiated with severity-dependent doses (≥900 mg) of D-penicillamine (DPA) or triethylene-tetramin-dihydrochloride (TRIEN). The motor score improved in 10 and remained constant in 8 patients. Worsening of neurological symptoms was observed only in two patients who developed comorbidities (myasthenia gravis or hemispheric stroke). The neurological symptoms continuously improved over the years until the majority of patients became only mildly affected. In contrast to this slow recovery of the neurological symptoms, the MELD score and liver enzymes had already started to improve after 1 month and rapidly improved over the next 6 months in 19 patients. The cholinesterase levels continued to increase significantly (<i>p</i> < 0.0074) even further. One patient whose MELD score indicated further progression of liver disease received an orthotopic liver transplantation 3 months after the diagnosis of WD and the onset of DPA treatment. Conclusions: Neurological and hepatic symptoms both respond to copper chelation therapy. For patients with acute liver failure, the first 4 months are critical. This is the time span in which patients have to wait either for a donor organ or until significant improvement has occurred under conventional therapy. For patients with severe neurological symptoms, it is important that they are treated with fairly high doses over several years. |
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| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-11T00:57:18Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
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| spelling | doaj.art-05bcabc7b7924e548d60326ce7b978dc2023-11-18T19:55:05ZengMDPI AGJournal of Clinical Medicine2077-03832023-07-011214486110.3390/jcm12144861Differences in the Time Course of Recovery from Brain and Liver Dysfunction in Conventional Long-Term Treatment of Wilson DiseaseHarald Hefter0Theodor S. Kruschel1Max Novak2Dietmar Rosenthal3Tom Luedde4Sven G. Meuth5Philipp Albrecht6Christian J. Hartmann7Sara Samadzadeh8Departments of Neurology, University of Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, GermanyDepartments of Neurology, University of Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, GermanyDepartments of Neurology, University of Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, GermanyDepartments of Neurology, University of Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, GermanyDepartments of Gastroenterology, University of Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, GermanyDepartments of Neurology, University of Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, GermanyDepartments of Neurology, University of Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, GermanyDepartments of Neurology, University of Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, GermanyDepartments of Neurology, University of Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, GermanyBackground: The aim of this study was to demonstrate that both neurological and hepatic symptoms respond to copper chelation therapy in Wilson disease (WD). However, the time course of their recovery is different. Methods: Eighteen patients with neurological WD from a single specialized center who had been listed for liver transplantation during the last ten years and two newly diagnosed homozygous twins were recruited for this retrospective study. The mean duration of conventional treatment was 7.3 years (range: 0.25 to 36.2 years). A custom Wilson disease score with seven motor items, three non-motor items, and 33 biochemical parameters of the blood and urine, as well as the MELD score, was determined at various checkup visits during treatment. These data were extracted from the charts of the patients. Results: Treatment was initiated with severity-dependent doses (≥900 mg) of D-penicillamine (DPA) or triethylene-tetramin-dihydrochloride (TRIEN). The motor score improved in 10 and remained constant in 8 patients. Worsening of neurological symptoms was observed only in two patients who developed comorbidities (myasthenia gravis or hemispheric stroke). The neurological symptoms continuously improved over the years until the majority of patients became only mildly affected. In contrast to this slow recovery of the neurological symptoms, the MELD score and liver enzymes had already started to improve after 1 month and rapidly improved over the next 6 months in 19 patients. The cholinesterase levels continued to increase significantly (<i>p</i> < 0.0074) even further. One patient whose MELD score indicated further progression of liver disease received an orthotopic liver transplantation 3 months after the diagnosis of WD and the onset of DPA treatment. Conclusions: Neurological and hepatic symptoms both respond to copper chelation therapy. For patients with acute liver failure, the first 4 months are critical. This is the time span in which patients have to wait either for a donor organ or until significant improvement has occurred under conventional therapy. For patients with severe neurological symptoms, it is important that they are treated with fairly high doses over several years.https://www.mdpi.com/2077-0383/12/14/4861Wilson diseasespectrum of symptomsrecoverycholinesterasebiomarkerorthotopic liver transplantation |
| spellingShingle | Harald Hefter Theodor S. Kruschel Max Novak Dietmar Rosenthal Tom Luedde Sven G. Meuth Philipp Albrecht Christian J. Hartmann Sara Samadzadeh Differences in the Time Course of Recovery from Brain and Liver Dysfunction in Conventional Long-Term Treatment of Wilson Disease Journal of Clinical Medicine Wilson disease spectrum of symptoms recovery cholinesterase biomarker orthotopic liver transplantation |
| title | Differences in the Time Course of Recovery from Brain and Liver Dysfunction in Conventional Long-Term Treatment of Wilson Disease |
| title_full | Differences in the Time Course of Recovery from Brain and Liver Dysfunction in Conventional Long-Term Treatment of Wilson Disease |
| title_fullStr | Differences in the Time Course of Recovery from Brain and Liver Dysfunction in Conventional Long-Term Treatment of Wilson Disease |
| title_full_unstemmed | Differences in the Time Course of Recovery from Brain and Liver Dysfunction in Conventional Long-Term Treatment of Wilson Disease |
| title_short | Differences in the Time Course of Recovery from Brain and Liver Dysfunction in Conventional Long-Term Treatment of Wilson Disease |
| title_sort | differences in the time course of recovery from brain and liver dysfunction in conventional long term treatment of wilson disease |
| topic | Wilson disease spectrum of symptoms recovery cholinesterase biomarker orthotopic liver transplantation |
| url | https://www.mdpi.com/2077-0383/12/14/4861 |
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