Liver transplantation as a treatment for Wilson\u2019s disease with neurological presentation: a systematic literature review

Agnieszka Antos,Jan Bembenek,Marta Skowrońska,Anna Członkowska,Tomasz Litwin,Adam Przybyłkowski,Iwona Kurkowska-Jastrzębska

doi:10.1007/s13760-022-01872-w

Agnieszka Antos, Jan Bembenek + Show 5 more

Open Access

https://doi.org/10.1007/s13760-022-01872-w

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Abstract

IntroductionWilson’s disease (WD) is a potentially treatable, genetic disorder of copper metabolism, with survival similar to healthy populations if controlled. However, in almost 50% of WD patients, neurological symptoms persist despite treatment, and in up to 10% of patients, neurological deterioration is irreversible. International guidelines on WD treatment do not recommend liver transplantation (LT) as a treatment for neurological symptoms in WD. However, such treatment has been assessed in retrospective analyses, case and series reports. We aimed to systematically assess all available evidence on the effectiveness and safety of LT in WD patients with neurological presentation.MethodsThis systematic literature review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were identified by searching the PubMed database (up to 6 April 2021) and by screening reference lists.ResultsBased on the systematic literature review, 48 articles were identified, showing outcomes of LT in 302 WD patients with neurological symptoms. Of these patients, major improvement was found in 215 cases (71.2%), with no difference in neurological status before and after LT in 21 cases (6.9%). There were 29 deaths (9.6%), neurological worsening in 24 cases (7.9%), and 13 cases (4.3%) were lost to follow-up.ConclusionsThe results suggest that LT is a promising method of WD management in patients with severe, neurological symptoms, particularly if the patient has not responded to pharmacological de-coppering treatment. Further studies of LT in these patients are warranted.

Highlights

Wilson’s disease (WD) is a potentially treatable, genetic disorder of copper metabolism, with survival similar to healthy populations if controlled
48 full-text articles of liver transplantation (LT) in 302 WD patients with neurological symptoms were included in the analysis
No prospective studies were identified, and there were 24 retrospective studies on patients with WD treated with LT; 23 of them were additional analyses of neurological symptoms in WD patients undergoing LT due to liver failure and only 1 was an analysis of neurological symptoms after LT in WD patients transplanted due to neurological deterioration (Table 1)

Summary

Introduction

Wilson’s disease (WD) is a potentially treatable, genetic disorder of copper metabolism, with survival similar to healthy populations if controlled. International guidelines on WD treatment do not recommend liver transplantation (LT) as a treatment for neurological symptoms in WD Such treatment has been assessed in retrospective analyses, case and series reports. Results Based on the systematic literature review, 48 articles were identified, showing outcomes of LT in 302 WD patients with neurological symptoms. Of these patients, major improvement was found in 215 cases (71.2%), with no difference in neurological status before and after LT in 21 cases (6.9%). Conclusions The results suggest that LT is a promising method of WD management in patients with severe, neurological symptoms, if the patient has not responded to pharmacological de-coppering treatment. Copper-induced lipid peroxidation leads to mitochondria membrane damage, subsequent disruption of respiratory chain enzymes, and hepatocyte necrosis, with release into the circulation of free non-ceruloplasminbound copper (NCC) [1,2,3,4,5].

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