Summary of one article: Diagnosis and treatment of hepatolenticular degeneration (Wilson disease) | Clinical Essentials

Introduction Hepatolenticular degeneration, also known as Wilson's disease (WD), is an autosomal recessive genetic disease caused by mutations in the ATP7B gene.

WD can cause excessive accumulation of copper in the patient's body, which mainly affects the basal ganglia of the liver and brain, as well as other organ systems.

According to the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) estimates, about 1/30000 people worldwide suffer from the disease.

my country currently lacks a large-sample multi-center WD incidence survey, but there is a literature analysis that the incidence of this disease is higher in China than in Western countries.

This article summarizes the clinical manifestations, diagnosis and treatment of WD in detail.

The clinical manifestations of WD Before the accumulation of copper in the body to an excessively high level, the patient may not show obvious symptoms.

Symptoms of WD may be widespread, affecting the liver, nervous system, brain, eyes, or other organs.

Patients with liver symptoms may have the following accompanying symptoms of liver disease: jaundice, liver pain, dark urine, white stools, fatigue, nausea, and vomiting.

Some patients may develop symptoms only when they develop complications of chronic liver disease and cirrhosis, including: weakness and fatigue, unexplained weight loss, ascites or abdominal distension due to fluid accumulation, lower extremity swelling, jaundice, and skin itching.

Patients with nervous system and mental health symptoms may also experience neurological symptoms due to high levels of copper in the body.

These symptoms are more common in adults, but can also affect children.

In about 40%-50% of WD patients, the first symptoms may be related to the central nervous system, including: tremor, muscle stiffness, physical coordination, speech and swallowing difficulties.

In addition, patients may also experience anxiety, psychosis, depression, behavioral and personality changes and other manifestations.

Ocular symptoms Copper deposits in the eyes can cause the Kayser-Fleischer ring to appear around the cornea, which may be green, gold or brown in color.

The Wilson's Disease Association pointed out that the Kayser-Fleischer ring will affect approximately 95% of patients with neurological symptoms and 65% of patients with liver symptoms.

The doctor who diagnoses WD can diagnose WD based on the patient's medical history and examination results.

Knowing that the patient has a family history of WD may help doctors make a diagnosis faster.

The examination includes the following items: Eye examination: Check the Kayser-Fleischer ring.

Physical examination: Check for skin changes, enlarged liver, swelling of the abdomen and lower limbs, and jaundice.

24-hour urine test: Check the copper content in the urine.

Liver biopsy: If the results of blood and urine tests are not clear, the doctor can perform a liver biopsy on the patient to check the degree of liver damage and determine the copper content in the tissue.

Imaging examination: If the patient has neurological symptoms, doctors can use MRI and CT examinations.

Blood tests: check ceruloplasmin levels, copper levels, liver enzymes (alanine aminotransferase and aspartate aminotransferase), red blood cells (check for anemia).

Treatment of WD WD is one of the few treatable genetic diseases.
The treatment methods mainly include diet control, medication and liver transplantation.

If the diagnosis can be made early and the low-copper diet and copper excretion treatment can be started early, the patient can achieve remission of the disease, and obtain a good quality of life and a survival period similar to that of normal people, without liver transplantation.

Once dietary control WD is diagnosed, life-long treatment is required, because stopping treatment means that copper will accumulate again.

During the initial treatment period, patients should avoid foods rich in copper, including: chocolate, liver, mushrooms, nuts, shellfish, dried beans, dried fruits, foods containing whole grains, etc.

In addition, the patient should also check whether the water supply in the home passes through the copper pipe to prevent it from affecting their drinking water.

When the copper content in the patient's body is at a safe level, you should consult a doctor to determine whether you can start to consume copper-rich foods.

Patients should also consult their doctor before taking any supplements, as these supplements may contain copper.

The British Liver Trust pointed out that WD patients should avoid drinking alcohol to avoid aggravating the condition.

Drug therapy The drugs currently used to treat WD include penicillamine, trientine, ammonium tetrathiomolybdate, and zinc.

In Western countries, trientine has been replaced by penicillamine as the preferred drug, but the drug has not yet been used in my country.

At present in my country, penicillamine, dimercaptosuccinic acid, and zinc are still the most commonly used copper excretion drugs.

Penicillamine is the first drug used to treat WD, and a large number of studies have confirmed its curative effect.

It can treat WD by promoting urinary copper excretion.
The usual dose is 750-1500 mg/d, administered in 2-3 times.

Take 1h before meals.

Most patients with liver disease as the main manifestation have significant improvement in liver function 2-6 months after treatment.
After maintenance treatment for more than 1 year, the condition tends to be stable.
When the condition is stable, the dose can be reduced or intermittent medication.

Dimercaptosuccinic acid is a broad-spectrum metal antidote and is a chelating agent.

After the drug enters the liver, it can complex the copper deposited in the liver, improve the liver's copper metabolism and increase the bile flow rate.

Studies have shown that its copper-removing effect is slightly lower than penicillamine, but its adverse reactions are very mild, with only a few digestive tract reactions and neutropenia.

In addition, the drug treatment of WD will not aggravate neurological symptoms, and is more suitable for neurological and mild WD.

Zinc can interfere with the intestinal uptake of copper.

The recommended dose is 150 mg/d of zinc.

Children weighing less than 50 kg are given zinc 75 mg/d, 3 times a day, 30 minutes before meals.

Whether combined with other chelating agents can improve the efficacy is not clear, but in order to avoid offsetting the effect of zinc, chelating agents should be administered at different times.

Acute liver failure or decompensated cirrhosis caused by liver transplantation WD usually requires liver transplantation.

Since biochemical abnormalities mainly exist in the liver, orthotopic liver transplantation can solve the fundamental problem.

The median survival time after orthotopic liver transplantation is 2.
5 years, and the longest survival time is 20 years.

However, liver transplantation cannot completely replace copper-expelling therapy.
Many patients still need a low-copper diet and copper-expelling therapy after liver transplantation.

References: [1] Chen Dawei, Zhang Min.
New progress in diagnosis and treatment of hepatolenticular degeneration[J].
Infectious Disease Information, 2019, 32(02):158-161.
[2] Hana Ames.
What is Wilson's disease , and how is it treated? MedicalNewsToday.
2021 Feb 25.
[3] Progress in the treatment of hepatolenticular degeneration (Wilson disease)[J].
China Medical Innovation, 2019, 16(04):6.
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