Major Research Findings

Wilson disease (WD) is a potentially fatal genetic disorder caused by copper buildup in the body, particularly in the liver, which can lead to a variety of symptoms including liver damage, neurological problems, psychiatric disorders, and eye problems. 10 While the condition is caused by a dysfunction in the copper transporter ATP7B, the specific mutations and copper levels in the liver alone cannot fully explain the wide range of symptoms seen in WD patients. 10 Recent research has unveiled new insights into WD's progression and the metabolic signatures of its different presentations. 10 Studies have revealed that non-parenchymal liver cells and tissues outside the liver contribute to liver problems in WD patients. 10 Furthermore, disruptions in nuclear receptors, epigenetic modifications, and mitochondrial dysfunction have emerged as key factors in the development of WD. 10 This review summarizes the latest advancements in understanding WD's pathophysiology and discusses promising new targets for improving diagnosis and treatment. 10

The Gandou decoction (GDD), a traditional Chinese medicinal formula, has been used for decades to treat WD. 18 It is a combination of different decoctions and was first documented in ancient Chinese medical texts. 18 Liver damage is a serious complication of WD. 18 A recent study aimed to explore the liver-protective effects of GDD and its specific therapeutic targets, with a particular focus on oxidative stress and the Wnt/β-catenin pathway. 18

Treatment Summary

Currently available treatments for WD aim to prevent the long-term complications of copper buildup. 21 Anti-copper agents commonly used include zinc salts, penicillamine, and trientine. 21 Patients with WD may switch between these agents for a variety of reasons. 21 The different mechanisms of action between copper chelators and zinc salts mean that transitioning between treatments might require a period of overlap and increased monitoring. 21 Large studies on the best transition strategies are lacking. 21 This article reviews the treatments for WD and methods for monitoring treatment effectiveness. 21 One case study describes a patient who successfully transitioned from penicillamine to zinc and then to trientine over a period of 20 years, demonstrating the need for personalized treatment and ongoing monitoring. 21 The study concludes that anti-copper treatment for WD must be tailored to the medication's side effects profile, the patient's existing and emerging health conditions, and the cost of treatment. 21 Switching treatment regimens is often challenging and requires close monitoring, with no clear predictors of how a patient will respond. 21

Research has shown that both neurological and liver problems respond to copper chelation therapy in WD. 5 However, the time it takes for these symptoms to improve varies. 5

A systematic review and meta-analysis of controlled studies aimed to compare the effectiveness and safety of common treatments for WD. 2 The study concluded that both neurological and hepatic symptoms respond to copper chelation therapy in Wilson disease (WD). 5 However, the time it takes for these symptoms to improve varies. 5

In Japan, WD is considered for individuals with liver abnormalities (excluding infants), those over 13 years old with neurological or neuropsychiatric disorders (especially those with extrapyramidal signs) with or without liver disease, and siblings of WD patients. 23 Diagnosis typically involves a combination of low serum ceruloplasmin levels and high urinary copper content. 23 Other diagnostic tests include measuring hepatic copper content and analyzing the ATP7B gene. 23 The primary treatment strategy is to reduce copper levels in the liver and other tissues through copper-chelating agents like D-penicillamine or trientine, and/or zinc acetate. 23 The authors recommend zinc acetate monotherapy for mild to moderate hepatic disorders, trientine monotherapy for mild to moderate neurological disorders, and a combination of trientine and zinc acetate for severe hepatic or neurological disorders. 23

Benefits and Risks

Benefits Summary

Treatments for WD can help improve symptoms and slow the progression of the disease by reducing copper buildup in the body. 25 Early diagnosis and timely treatment are crucial for better outcomes. 25 Continued treatment helps prevent the worsening of the disease. 22 Zinc is considered a safer option compared to penicillamine due to a lower risk of side effects. 3 However, zinc can interfere with copper absorption, potentially leading to copper deficiency. 4 Trientine has also been found to have fewer side effects compared to penicillamine. 11 But, trientine's effectiveness for liver problems may be limited. 11

Risk Summary

WD treatments carry the risk of side effects. 10 Penicillamine has a higher risk of side effects, including potentially serious ones like pseudoxanthoma elasticum. 17 Zinc can interfere with copper absorption, potentially leading to copper deficiency. 4 Trientine, while effective for neurological problems, may not be as effective for liver problems. 11 Therefore, selecting the right treatment based on the individual patient's needs is crucial. 11 While treatment persistence is vital for managing WD, it can be challenging. 22 Some patients might discontinue treatment or experience resistance to treatment. 22 Patient understanding and cooperation are essential for continued treatment. 22

Comparison Across Studies

Similarities Across Studies

Many studies agree that copper chelating agents and zinc are effective treatments for WD. 10 Continued treatment is crucial for managing WD and preventing the worsening of the disease. 22 Furthermore, choosing the right treatment based on each patient's individual condition is essential. 11

Differences Across Studies

There are differences in the conclusions drawn from studies regarding the effectiveness and safety of penicillamine and zinc. 3 Additionally, since WD treatment varies depending on the individual patient's condition, the same treatment approach may not be effective for everyone. 25

Consistency and Contradictions in Findings

Research on WD treatment is still limited, and more studies are needed to fully assess the effectiveness and safety of different treatments. 25 The development of new treatment options remains a crucial area for further research. 25

Practical Implications and Considerations

WD treatment should be overseen by a specialist physician. 25 Before starting treatment, patients should discuss their treatment options and potential side effects thoroughly with their doctor. 25

Limitations of Current Research

Research on WD treatment is still limited, and more studies are needed to fully assess the effectiveness and safety of different treatments. 25 The development of new treatment options remains a crucial area for further research. 25

Future Research Directions

Research on WD treatment is still limited, and more studies are needed to fully assess the effectiveness and safety of different treatments. 25 The development of new treatment options remains a crucial area for further research. 25 Understanding the mechanisms underlying the development of WD could pave the way for more effective treatment strategies. 10

Conclusion

Early diagnosis and timely treatment are crucial for managing WD, improving symptoms, and slowing the progression of the disease. 25 Continued treatment is essential for preventing the worsening of the disease. 22 The right treatment needs to be selected based on the individual patient's condition. 11 Treatment should always be overseen by a specialist physician. 25

Treatment List

D-penicillamine, Trientine, Zinc, Copper Chelators, Copper Absorption Inhibitors, Ammonium Tetrathiomolybdate