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From neonatal jaundice to cirrhosis, how does A1AD affect your liver?
In many people's minds, liver health is often seen as directly related to diet and lifestyle habits. However, the reasons behind many liver diseases may be genetic. For example, Alpha-1 Antitrypsin Deficiency (A1AD), a genetic disease caused by mutations in the SERPINA1 gene, can have profound effects on a patient's liver health.
Effects of alpha-1 antitrypsin deficiencyThe main lung and liver problems in A1AD usually appear between the ages of 20 and 50, with symptoms including difficulty breathing, wheezing and an increased risk of lung infections. More serious cases may be associated with chronic obstructive pulmonary disease (COPD), cirrhosis of the liver, and neonatal jaundice. For newborns, A1AD may cause early jaundice, which may then lead to persistent jaundice, posing a threat to the health of the sick baby.
Among newborns, approximately 3% to 5% of children with the ZZ mutation develop life-threatening liver disease, including liver failure.
The impact of A1AD on the liver is mainly due to the abnormal accumulation of mutated α1 antitrypsin (A1AT) in the liver, leading to liver cell damage. Usually, this abnormal protein secreted incorrectly from glandular cells causes liver fibrosis or cirrhosis, and severe cases require a liver transplant. The main cause of this condition is the difference in genotype, especially the PiZZ genotype has the most significant impact in this regard.
Genetics and Pathophysiology
Alpha-1 antitrypsin deficiency is caused by mutations in the SERPINA1 gene, which is located on chromosome 14. Mutations in this gene may lead to insufficient production of A1AT, which in turn affects lung and liver function. Under normal circumstances, A1AT can inhibit neutrophil elastase and protect the lungs from its damage. However, when A1AT is deficient, these enzymes destroy the elastic tissue in the lungs, leading to the development of lung-related diseases.
85% of the mutated Z-type A1AT cannot be secreted normally and eventually accumulates in liver cells, causing liver damage.
Diagnosis and treatment
The diagnosis of A1AD is usually based on a blood test that assesses the level of A1AT, or further genotyping. For patients with liver disease, liver biopsy remains the gold standard for evaluating liver fibrosis and cirrhosis. Despite this, many patients are misdiagnosed with COPD without receiving a correct diagnosis.
Once diagnosed, treatment strategies may include the use of bronchodilators, inhaled steroids and antibiotics. In addition, IV infusion of A1AT protein or lung transplantation in severe cases are also treatment options. For patients with liver disease, they need to control their diet, avoid drinking alcohol and have regular checkups to prevent their condition from worsening.
EpidemiologyReducing smoking and getting vaccinated against influenza, pneumonia, and hepatitis are especially important for people with A1AD.
The incidence of A1AD is higher in Northern European and Iberian populations, with approximately 4% of people carrying the PiZ allele. It is estimated that more than 1.1 million people are affected by the disease worldwide, with the most frequent PiZZ variant being more pronounced in northern and western European countries.
Postscript and Research Prospects
Since A1AD was first described in 1963, scientists have continued to work to understand the deeper mechanisms behind the disease. As research deepens, treatment for recombinant and inhaled A1AT is ongoing, and future treatment options may significantly change the quality of life of patients. Has your understanding of liver disease changed today because of this knowledge?
