Genetic Liver Diseases

Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder affecting the lungs, liver and rarely, skin. In the lungs, AAT deficiency causes early onset emphysema. The liver disease due to AAT deficiency is caused by an accumulation of abnormal AAT protein, which leads to progressive liver injury.

Adults with liver involvement may have no symptoms until they develop advanced cirrhosis. The diagnosis is suggested by a low AAT level whereby further genetic testing can confirm the diagnosis. A liver biopsy can help confirm the diagnosis. Management focuses on supportive measures to prevent or reduce the complications of chronic liver disease. For adults with end-stage liver disease due to AAT deficiency, liver transplantation results in excellent five-year survival rates.

Hereditary Hemochromatosis

Hereditary hemochromatosis (HH) is caused by a genetic defect and leads to increased iron absorption in the small intestine. The clinical complications of HH are related to large amounts of iron deposition in the liver, heart, pancreas, and pituitary.

Most patients are identified by abnormal iron values on routine blood work. The symptoms associated with HH are typically nonspecific such as fatigue. More organ-specific symptoms are joint pain, symptoms related to complications of chronic liver disease, diabetes and congestive heart failure. The diagnosis is usually made through laboratory test results; however, a liver biopsy may sometimes be necessary.

The treatment of HH is phlebotomy (removing blood and therefore iron from the body). With adequate treatment, in general patients feel better, with less fatigue. In addition, in patients that have not developed cirrhosis, the associated liver injury can regress, the enlargement of the liver as well as the liver test elevation improve. The heart function may also improve.

The most common causes of death in HH are related to the complications of cirrhosis and liver cancer. Patients who are treated early should not develop these complications; therefore, early diagnosis is important. Once a patient is identified to have HH, all first-degree relatives should be offered screening with genetic testing.

Wilson Disease

Wilson disease is a rare genetic condition which leads to copper overload in the liver. The impaired copper removal from the bile ducts in the liver leads to accumulation of copper in several organs, most notably the liver, brain, and cornea. Over time, the liver is progressively damaged leading to cirrhosis. A small percent of patients develop acute liver failure, where the liver rapidly fails and those patients almost always require liver transplantation, which cures this disease.

Wilson disease typically affects young individuals. The symptoms of Wilson disease include rapid liver failure, sudden or chronic elevation of liver enzymes (indicating liver inflammation), cirrhosis, and fatty liver. Since the excess copper can also accumulate in the brain, patients with Wilson disease can have neurologic and psychiatric symptoms.

A liver biopsy is almost always needed to establish the diagnosis and determine the amount of liver damage. The mainstay of treatment has been copper-chelating (binding) therapies. Untreated, Wilson disease is universally fatal. Copper accumulation in the liver eventually leads to the development of cirrhosis with its associated complications. Patients with neurologic Wilson disease may progress until the patient becomes severely disabled. Genetic testing is used to identify the specific genetic mutation to screen siblings.

The prognosis for patients who receive and are adherent to treatment for Wilson disease is excellent, even in some who already have advanced liver disease. Among patients requiring liver transplantation, survival following transplantation is excellent and cures the disease.