What is hepatomegaly (Wilson’s disease) Wilson’s hepatomegaly (hepatolenticulardegeneration, HLD), also known as Wilson’s disease, is an autosomal recessive disorder of copper metabolism. First reported and described by Wilson, it is an inherited disorder of copper metabolism resulting in cirrhosis of the liver and a degenerative disease of the brain with a predominantly basal ganglia. Clinically, it presents with progressively worsening extrapyramidal symptoms, cirrhosis, psychiatric symptoms, renal impairment, and corneal pigment ring K-F ring. What causes hepatomegaly (Wilson’s disease) The specific manifestations of impaired copper metabolism in this disease include a decrease in total serum copper and copper cyanine and an increase in the amount of copper in the loosely bound fraction, a decrease in hepatic excretion of copper into the bile, an increase in urinary copper excretion, and excessive copper deposition in many organs and tissues, especially in the liver, brain, cornea, and kidney. Excessive copper deposition can damage the tissue structure and function of these organs and cause disease. Mechanisms of impaired copper metabolism in hepatomegaly Copper is involved in the synthesis of many important biological enzymes as a cofactor. In normal subjects, most of the copper absorbed into the blood from the intestine is first loosely bound to albumin and then enters the hepatocytes. In hepatocytes, copper is transported to Golgi bodies by P-type copper-transporting ATPase, which is then firmly bound to α2 globulin to form copper cyanobactin, which is then secreted into the blood. Circulating copper is 90-95% bound to copper cyanine. 70% of copper cyanine is present in plasma and the remainder is present in tissues. The excess copper is excreted from the body mainly as copper cyanine from the bile. Patients with this disease are unable to transport copper to Golgi bodies to synthesize copper cyanobacteria due to defective P-type copper-transporting ATPase. Excess copper accumulates in hepatocytes causing hepatocyte necrosis, and the copper it contains enters the bloodstream and is then deposited in extrahepatic tissues such as the brain, kidney, and cornea, causing the disease. What are the symptoms of hepatomegaly (Wilson’s disease)? Most of the symptoms of this disease appear between the ages of 10 and 25, with more men than women, and there are often patients with the same disease in their siblings. The main symptoms are: a. Neurological symptoms: The first symptom is often a subtle tremor, a slight slurred speech or slow movement, which is gradually aggravated and followed by new symptoms. The typical symptoms are mainly extrapyramidal symptoms, such as increased tonicity of the extremities, slow movement, mask-like face, muffled speech, salivation, chewing and swallowing difficulties. The most common involuntary movements are tremors, which are often evident during activities, and in severe cases, the head and trunk can be affected in addition to the limbs. Mental symptoms include emotional instability and mental retardation, and in severe cases, the face is expressionless, the mouth is often open, and the intelligence declines. A few may have tendon reflex hyperactivity and cone bundle signs, and some may have seizure-like epilepsy. Liver symptoms: Childhood patients often have liver disease as the first symptom, and adult patients can trace the history of “hepatitis”. The liver is enlarged, hard and painful to the touch, and liver damage may gradually increase with symptoms of cirrhosis, splenomegaly, hypersplenism, ascites, rupture of esophageal varices and hepatic coma. Corneal pigment ring: brownish-yellow or greenish-brown pigment ring about 2-3mm wide can be seen at the edge of the cornea, and fine pigment particles can be deposited by slit lamp examination, which is an important sign of the disease and is usually seen after the age of 7. Renal damage: proteinuria, glycosuria, amino aciduria, uric aciduria and nephrogenic rickets may occur due to damage to renal tubules, especially proximal tubular epithelial cells. V. Hemolysis. Hemolysis can occur simultaneously with other symptoms or alone, due to excessive release of copper into the bloodstream and damage to red blood cells. What tests are needed for hepatomegaly (Wilson’s disease) 1. Blood copper test. Total serum copper is reduced. 2.Urine examination. Urinary copper excretion is increased. Penicillamine load test is useful for diagnosis, especially for the detection of pre-symptomatic and early stage patients. 3.Abnormal liver function, anemia, reduced white blood cells and platelets. 4.Cranial CT examination, abnormal hypointense shadow can be seen in the bilateral nucleus accumbens area, and there can be hypointense area in the head of caudate nucleus, cerebellar dentate nucleus area and brainstem, and the cerebral cortex and cerebellum can show atrophic changes. 5.Electroencephalogram abnormalities. 6.Tissue micro-copper measurement. I. Serum copper blue protein can be examined by enzymatic or immunochemical methods, with normal values of 1.3-2.6 μmol/L (20-40 mg/dL). In patients showing only liver damage, 85% are below 1.3 μmol/L, but reduced copper cyanobalin is not a diagnostic indicator of Wilson’s disease per se. Heterozygotes have low serum copper blue protein levels, 25% of those with chronic active hepatitis have low serum copper blue protein, and 15% of those with Wilson’s disease with severe chronic active liver disease have normal serum copper blue protein. Second, non-copper blue protein serum copper normal people with albumin and amino acid binding of copper 15-20μg / L, untreated Wilson disease patients with serum copper levels of this type up to 500μg / L, but other liver and biliary lesions can also be elevated, and thus the diagnostic value is not large. Third, urinary copper is <40μg/24h in normal people, and up to 100μg/24h or more in Wilson's disease after stage I or with clinical manifestations; occasionally increased to >1000μg/24h in stage II patients. However, other cirrhosis, chronic active hepatitis, cholestasis including primary biliary cirrhosis can also be elevated, so the diagnostic value is not great, but it can be used as an indicator to follow the effect of D-penicillamine treatment. Fourth, the normal level of liver copper is 15-55μg/g dry weight, untreated Wilson disease up to 250-3000μg/g dry weight, <250μg/g dry weight can be excluded from Wilson disease. However, primary biliary cirrhosis, primary sclerosing cholangitis, extrahepatic bile duct obstruction, bile duct atresia, intrahepatic cholestasis or other biliary tract diseases can lead to increased hepatic copper, thus increased hepatic copper by itself is of little value for the diagnosis of Wilson's disease. E. Radionuclide copper infiltration test can be used in cases of diagnostic difficulties, such as Wilson's disease with normal copper cyanobacteria, heterozygotes with genetic defects, other diseases accompanied by K-F ring, increased hepatic and urinary copper, and when liver puncture biopsy is not allowed. In normal people, a high number of Cu2mg is observed 1~2h after oral administration, and then it decreases, followed by a slow rise within 48h when 64Cu is involved in copper cyanine synthesis and released into the blood. In Wilson's disease, there is a peak at the beginning of 1 to 2 h, but after the decline, 64Cu is rarely or not at all involved in the synthesis of copper blue protein, so the serum radioactivity no longer increases. How to treat The disease can be treated, but it cannot be cured The most common treatment methods used in most hospitals are as follows: a. Low copper, high protein diet. Avoid foods with high copper content such as crustaceans, nuts, beans, chocolate, kiwis, kullei pears, animal liver, blood, etc. Forbid the use of high copper drugs such as turtle plate, turtle nail, pearl, oyster, stiletto, and dilaudid. Second, the use of pharmaceutical drugs to repel copper: (a) D-penicillamine. Should be taken for a long time, 20-30mg/kg per day, divided into 3-4 times in half an hour before meals orally. (B) triethyltetramine. Adverse reactions to penicillamine can be changed to this drug, long-term application may cause iron deficiency. (C) Dimercaptopropanol. (iv) Zinc sulfate. It is less toxic and can be taken for a long time. Take 200mg half an hour before meal, 3/d. When combined with D penicillamine, take them at least 2h apart to prevent zinc ions from being complexed by D penicillamine in the intestinal tract. Three, symptomatic treatment: (a) liver protection therapy. Multivitamins, energy combination, etc. (B) for the extrapyramidal symptoms, can use antan or ranuncine. (C) such as hemolytic episodes, available adrenocorticotropic hormone or plasma replacement therapy. (D) surgical treatment of liver transplantation, although not a complete treatment of the disease. Because the disease is not a problem with the liver itself, but chromosomes, a genetic disease. However, severe loss of liver function or severe cirrhosis can be considered for liver transplantation to prolong its life. Except for gene therapy, which is still under research, there is no treatment that can completely cure this disease. Moreover, if a patient has a liver transplant, copper repellent therapy is not available. Therefore some patients with early to mid-stage liver transplantation often have shorter lives than other early to mid-stage non-surgical treatments and have to take a lot of rejection drugs. Therefore, liver transplantation is not promoted unless there is loss of liver function and severe sclerosis! The disease needs to be diagnosed and treated early, and copper is artificially induced to be excreted from the patient's body. If the copper is not excreted over time, it will accumulate in the patient's body and cause chemical reactions in the surrounding organs, causing organic changes in the organs. At that time, the treatment with the help of copper excretion can only prevent the organ from continuing to be diseased, but the damage caused by the previous copper deposition can no longer be repaired, and the patient will be left with lifelong symptoms and can only rely on continuous treatment and medication to maintain normal movement. The main drugs used to promote copper excretion in the patient's body are chemical drugs such as penicillamine, dimercaptopropanol, and sodium dimercaptosuccinate. The most effective treatment is the long-term oral administration of penicillamine tablets, which should be kept within the range of 0.6 to 1.5 grams per day for adults and 0.3 to 0.8 grams per day for children. In addition, patients need to pay attention to their diet and try to avoid foods with high copper content (hard-shelled fruits, shellfish, mushrooms, legumes, and blood or liver of animals). Research in recent years has revealed that hepatomegaly is caused by a mutation in a gene called ATP7B located on the thirteenth chromosome pair. The product of this gene is thought to be a protein associated with the transport of copper, which is abundant in the liver, and its deficiency leads to a decrease in copper excretion from the bile, which in turn accumulates in the liver leading to copper toxicity and death of liver cells. The large amount of copper released from the liver is then circulated to other organs of the body through the bloodstream, and large amounts of copper accumulate in each organ. Current medications are designed to speed up the elimination of copper from the body, but avoiding copper-containing foods such as beans, shelled seafood, chocolate, nuts, brown rice, and vitamin B6 supplements can also help slow the disease. The current treatment is the use of ChelationTherapy to remove copper from the patient's body. Zinc intake can help reduce the absorption of copper in the small intestine. Although treatments are available, only 0.4% of patients respond effectively to treatment. Liver transplantation is arguably the most effective radical cure, as the vast majority of protein deficiencies caused by genetic defects occur in the liver, so transplanting a liver usually cures Willebrand's disease. Patients with Reye's disease require long-term treatment and can have a mortality rate of 99.96% without any treatment.