Introduction:
The liver is an essential organ that performs the most substantial functions. The liver controls the synthesis of proteins, other biochemical substances, glycogen storage, and hormone production. The liver is a complex organ, and it is also prone to many diseases. Many acquired as well as genetic conditions can affect the liver. The consequences of liver disease can be life-threatening. Diseases that affect the liver are hepatitis, alcoholic fatty liver, liver cancer, hemochromatosis, Wilson's disease, etc.
What Is a Metabolic Disease of the Liver?
A group of metabolic diseases can cause the liver to function abnormally. These disorders can affect the function of liver cells, and as a result, the metabolic pathways influencing absorption, transportation, and nutrition storage are hampered. This ultimately causes liver failure.
The Group of Diseases That Causes Metabolic Liver Disease Are:
1. Wilson’s disease.
2. Alpha-1 antitrypsin deficiency.
3. Hereditary hemochromatosis.
4. GALD (gestational alloimmune liver disease).
5. Glycogen storage deficiencies.
6. Galactosemia.
7. Tyrosinemia.
What Causes Metabolic Liver Disease?
As mentioned above, an array of conditions cause metabolic liver disease. Most of these are linked to genetic mutations.
The conditions are:
1. Wilson’s Disease - It is a rare genetic disorder that leads to the accumulation of copper in the liver, brain, and other organs. The elimination of copper does not occur, and it accumulates in excessive amounts, leading to life-threatening consequences. Wilson’s disease affects one in 30,000 individuals. Wilson’s disease is diagnosed around the age of 5 to 35 years, but it can also affect older people. The cause of Wilson’s disease is due to the mutation in the ATP7B gene that is responsible for copper transportation in the body. The mutations cause a functional defect in copper metabolism, eventually leading to copper accumulation.
2. Alpha-1 Antitrypsin Deficiency - It is also an inherited condition that increases the risk of lung disease and kidney disease. This condition affects one in 1,500 to 3,500 individuals of European origin. The mutations in the SERPINA1 gene cause alpha-1 antitrypsin deficiency. This gene is responsible for producing alpha-1 antitrypsin, a protein that protects the body from an enzyme called neutrophil elastase. The enzyme neutrophil elastase fights against pathogens, but it can also attack lung tissue. When the protective alpha-1 antitrypsin is deficient, neutrophil elastase damages the lungs. Alpha-1 antitrypsin deficiency causes liver disease in about 10 % of infants. Scar tissue formation in the liver causes liver damage in 15 % of adults with alpha-1 antitrypsin deficiency.
3. Hereditary Hemochromatosis - It is a hereditary disorder characterized by excessive absorption of iron from the diet. Humans cannot excrete excess iron, and therefore, the excess iron gets deposited in the heart, liver, skin, and pancreas. Hereditary hemochromatosis is also called iron overload disorder. There are several types of hemochromatosis (type 1, type 2, type 3, and type 4), and type 1 is the most common. The other types are comparatively rare. The mutations in the gene HFE are responsible for type 1 hemochromatosis. Type 1, 2, and 3 hereditary hemochromatosis are inherited as an autosomal recessive (the abnormal gene is inherited from both parents) pattern. Type 4 is inherited as an autosomal dominant pattern (the abnormal gene inherited from only one parent).
4. GALD (Gestational Alloimmune Liver Disease) - GALD is characterized by antibody production by the mother that attacks fetal liver cells. This condition affects four individuals per 1,00,000 live births. Some women develop specific anti-fetal liver IgG (immunoglobulin G) antibodies after sensitizing to fetal liver antigens. These antibodies trigger the terminal complement cascade (part of the immune system responsible for various inflammatory responses) in hepatocytes (liver cells) when they are delivered to the circulatory system of the fetus. GALD varies in severity and the survival rate of the fetus depends on the extent of the disease. Understanding the pathology of GALD has led to an increased survival rate in recent years.
5. Glycogen Storage Deficiencies (GSD) - It is a rare genetic disorder that affects the processing of glycogen (a type of sugar). Children with GSD lack enzymes that process glycogen. When glycogen is not broken down to glucose, it builds up in the liver, muscles, etc. The condition can affect children as well as adults.
6. Galactosemia - Galactosemia is a genetic disorder caused due to mutations in GALT, GALK1, and GALE genes. The enzymes responsible for the processing of galactose (a type of sugar) are produced under the instructions of these genes. The condition affects one in 30,000 to 60,000 births. If infants are not treated early, they develop several complications, including liver failure.
7. Tyrosinemia - It is a genetic disorder that causes disturbances in the breakdown of an amino acid called tyrosine. Tyrosine is the most important component of the body’s protein. As a result of this disruption, tyrosine builds up in the organs and leads to life-threatening complications. This condition is relatively rare and affects one in 1,00,000 infants. The fault lies in the mutated genes FAH, TAT, and HPD responsible for tyrosine metabolism.
What Are the Symptoms of Metabolic Liver Disease?
The symptoms of Metabolic liver disease vary depending on the type and severity of the affected condition. General presenting symptoms include:
1. Itching of the skin can be severe (pruritus).
2. The skin and sclera of the eye (whites of the eye) appear yellow.
3. Unexplained weight loss in infants and children.
4. Vitamin and nutritional deficiencies.
5. Scarring of the liver (cirrhosis).
6. Fatigue and generalized weakness.
7. Easy bruising and bleeding.
8. Pain, fullness, and swelling of the abdomen.
9. Low blood sugar levels (hypoglycemia).
What Is the Treatment for Metabolic Liver Disease?
The treatment of metabolic liver disease solely depends on identifying the underlying problem. Since several conditions can cause metabolic liver disease, targeting them would relieve the symptoms. The general management includes:
1. Changes in Diet - Avoiding food containing iron, copper, galactose, etc., can reduce the buildup of their byproducts in the liver and other organs.
2. Medications - Certain medications help transport the excess substances from the liver and other organs to the blood circulation. These products are then eliminated.
3. Phlebotomy - It is an intentional or therapeutic procedure where a surgical opening or puncture is made in the vein to remove the blood containing excess unprocessed substances.
4. Phototherapy - It is a type of treatment where a particular type of light is used to treat jaundice. The light changes the structure of bilirubin (a yellowish pigment produced as a result of red blood cell breakdown) into a more excretable form.
5. Liver Transplant - It is an effective option that improves the quality of life in children with hereditary errors of metabolism. Even after the transplant, children may require dietary restrictions and observation. Liver transplant surgery can also present several complications; therefore, strict preoperative and postoperative measures are necessary.
Conclusion:
Metabolic liver disease is a group of metabolic conditions that cause the liver to function abnormally. Most of these diseases are inherited, and their severity depends on the extent of the state. Commonly affecting disorders of metabolism include Wilson’s disease, hereditary hemochromatosis, alpha-1 antitrypsin deficiency, etc. The symptoms can vary from jaundice, fatigue, itchy skin, nutritional deficiencies, and liver and nutritional deficiencies to liver scarring (cirrhosis). Changes in diet, certain medications, phototherapy, etc., can give symptomatic relief. Identifying these conditions at the earliest improves the survival rate and quality of life to a greater extent.
