Liver

Non-alcoholic fatty liver disease (NAFLD) is a buildup of excessive fat in the liver that can lead to liver damage resembling the damage caused by alcohol abuse, but that occurs in people who do not drink heavily. The liver is a part of the digestive system that helps break down food, store energy, and remove waste products, including toxins. The liver normally contains some fat; an individual is considered to have a fatty liver (hepatic steatosis) if the liver contains more than 5 to 10 percent fat.

The fat deposits in the liver associated with NAFLD usually cause no symptoms, although they may cause increased levels of liver enzymes that are detected in routine blood tests. Some affected individuals have abdominal pain or fatigue. During a physical examination, the liver may be found to be slightly enlarged.

Between 7 and 30 percent of people with NAFLD develop inflammation of the liver (non-alcoholic steatohepatitis, also known as NASH), leading to liver damage.

NAFLD is a very common disorder, occurring in about 25 percent of the global population. Its prevalence is increasing along with the rising prevalence of obesity in industrialized societies, and it is now the most common chronic liver disorder in world.

The specific causes of NAFLD are unclear. Genetic variations and environmental factors contribute to the development of this complex disorder.

many genetic changes that may be associated with the development of NAFLD and NASH. Among these is a particular variation in the PNPLA3 gene. This gene provides instructions for making a protein called adiponutrin, which is found in fat cells (adipocytes) and liver cells (hepatocytes).

An increased risk of developing NAFLD can be passed through generations in families, but the inheritance pattern is unknown. Variations in several genes as well as lifestyle and environmental factors contribute to the risk of developing this complex disorder.

Congenital hepatic fibrosis is a disease of the liver that is present from birth. The liver has many important functions, including producing various substances needed by the body and breaking down other substances into smaller parts to be used or eliminated.

Congenital hepatic fibrosis is characterized by malformation of the bile ducts and the blood vessels of the hepatic portal system.

People with congenital hepatic fibrosis have an enlarged liver and spleen.

Congenital hepatic fibrosis may occur alone, in which case it is called isolated congenital hepatic fibrosis.

The total prevalence of syndromes that include congenital hepatic fibrosis as a feature is estimated to be 1 in 10,000 to 20,000 individuals.

Syndromes that include congenital hepatic fibrosis may be caused by changes in many different genes.

The various syndromes that include congenital hepatic fibrosis can have different inheritance patterns. Most of these disorders are inherited in an autosomal recessive pattern, which means both copies of the associated gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Rare syndromes involving congenital hepatic fibrosis may be inherited in an X-linked recessive pattern, in which the gene associated with the syndrome is located on the X chromosome, which is one of the two sex chromosomes.

Alagille syndrome is a genetic disorder that can affect the liver, heart, and other parts of the body.

One of the major features of Alagille syndrome is liver damage caused by abnormalities in the bile ducts. These ducts carry bile (which helps to digest fats) from the liver to the gallbladder and small intestine.

The estimated prevalence of Alagille syndrome is 1 in 70,000 newborns. This figure is based on diagnoses of liver disease in infants.

In more than 90 percent of cases, mutations in the JAG1 gene cause Alagille syndrome. Another 7 percent of individuals with Alagille syndrome have small deletions of genetic material on chromosome 20 that include the JAG1 gene.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered or deleted gene in each cell is sufficient to cause the disorder.

In approximately 30 to 50 percent of cases, an affected person inherits the mutation or deletion from one affected parent. Other cases result from new mutations in the gene or new deletions of genetic material on chromosome 20 that occur as random events during the formation of reproductive cells (eggs or sperm) or in early fetal development. These cases occur in people with no history of the disorder in their family.