Cryptogenic cirrhosis (Cryptogenic cirrhosis) - Genes KRT18 and KRT8

Cryptogenic cirrhosis is a disease that affects liver function. Affected individuals develop irreversible liver disease due to cirrhosis, usually in mid to late adulthood. Often in the early stages of cryptogenic cirrhosis, affected individuals have no symptoms because the liver has enough normal functioning tissue. The signs and symptoms are evident as the liver parenchyma is replaced by scar tissue. Affected individuals may experience fatigue, weakness, loss of appetite, weight loss, nausea, edema, dilation of blood vessels and jaundice. In addition, these individuals may develop portal hypertension. Cryptogenic cirrhosis can lead to type 2 diabetes and the development of hepatocellular cancer. It is estimated that cryptogenic cirrhosis accounts for between 5 and 30% of cases of cirrhosis.

Unlike most cases of cirrhosis, cryptogenic cirrhosis is not a consequence of previous viral infections (hepatitis C or B) or chronic alcohol consumption. Generally, cryptogenic cirrhosis is diagnosed when all other causes have been ruled cirrhosis. Many cases of cryptogenic cirrhosis are probably due to disease nonalcoholic fatty liver disease (NAFLD). In NAFLD, fat accumulates in the liver, altering its function. If fat accumulation causes inflammation and tissue damage of the liver, NAFLD progresses to nonalcoholic hepatic steatosis (NASH). The long - term inflammation in patients with NASH can result in the formation of scar tissue and a decrease in fat accumulation. As a result, individuals with NASH progresses to cirrhosis. Cryptogenic cirrhosis may also develop from autoimmune hepatitis, a situation that occurs when the malfunction of the body 's immune system attacks the liver, causing inflammation and liver damage.

In very rare cases, cryptogenic cirrhosis has been associated with mutations in genes KRT18 and KRT8, both located on the long arm of chromosome 12 (12q13), encoding certain keratins. Keratins are a group of tough fibrous proteins that form the structural framework of certain cells, particularly of cells that make up the skin, hair, nails, and the like tissues. People with these keratin gene mutations are more likely to have fibrous deposits in their livers than people without the mutations. These deposits alter the function of the liver, leading to cirrhosis. Mutations in these genes have also been found in people with other liver diseases. In many cases, the reason for cryptogenic cirrhosis is unknown.

Most cases of cryptogenic cirrhosis are not inherited. However, people with a family history of liver disease or autoimmune disease are at increased risk of developing these diseases and possibly cirrhosis. In individuals with a genetic mutation associated with keratin, the risk of cryptogenic cirrhosis appears to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that a copy of an altered gene in each cell is sufficient to increase the risk of developing cryptogenic cirrhosis. In these families, people inherit an increased risk of cryptogenic cirrhosis, not the disease itself.

Tests performed in IVAMI: in IVAMI perform detection of mutations associated with cryptogenic cirrhosis, by complete PCR amplification of the exons of KRT18 and KRT8 genes, respectively, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).