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Cryptogenic liver disease

Cryptogenic liver disease (also referred to as cryptogenic cirrhosis) is the name doctors give to liver disease in which the cause is unknown. Doctors are usually able to say what causes liver disease, whether it’s genetic, due to alcohol dependency or because of a viral infection such as hepatitis B or C. A diagnosis of cryptogenic liver disease is usually given when all other causes have been ruled out.

There is some evidence to show that cryptogenic liver disease is linked to a condition called non-alcohol related fatty liver disease (NAFLD), in which a build-up of fat in the liver stops it from working properly. When NAFLD progresses to the more serious form of the condition, non-alcohol related steatohepatitis (NASH), it can lead to the formation of scar tissue and cirrhosis. The theory that around 50% of cryptogenic cirrhosis is probably due to NASH is based on the presence of risk factors such as obesity (past or present). The remaining 50% of cases is probably due to a range of disorders where the liver suffers chronic injury with no symptoms, for no obvious cause. Some of the underlying causes of cryptogenic liver disease may be environmental toxins, autoimmune conditions, drugs or damage to the blood supply of the liver.

Like other disorders of the liver, cryptogenic liver disease causes damage to the liver which stops it working properly. As more damage occurs and the liver becomes increasingly inflamed, scar tissue (fibrosis) starts to form, gradually replacing the healthy tissue. It can spread throughout the liver, changing its shape and affecting how well it works. This is known as compensated cirrhosis.

If the damage continues, the liver will become unable to work properly (decompensated cirrhosis) and start to fail, leading to symptoms such as jaundice, weight loss, loss of appetite and build-up of fluid in the abdomen (ascites). Confusion may also occur.

People with cryptogenic liver disease may develop high blood pressure in the vein that supplies blood to the liver. This is known as portal hypertension. It can also lead to type 2 diabetes and increase the risk of liver cancer (hepatocellular carcinoma, or HCC).  Doctors assessing people will look for a cause or for conditions which could relapse in the future.

Reviewed by Dr Stephen Ryder, consultant hepatologist, Nottingham University Hospitals NHS Trust