Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoimmune diseases of the liver are chronic inflammatory diseases leading to an etiologically undefined immune-mediated attack aimed at the hepatocyte, small microscopic bile ducts, and the entire biliary system detectable by cholangiography, respectively. From the standpoint of clinical disease three entities can be distinguished: autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). These are not only different regarding their clinical profile but also differ in diagnostic strategy, therapeutic regimen and probability of remission, as well as their association with other immune-mediated diseases and cancer. PBC and PSC are cholestatic diseases. PBC is most often diagnosed in women. The diagnosis is readily reached by the detection of specific antimitochondrial autoantibodies directed against pyruvate dehydrogenase (PDH-E2), is associated with an array of rheumatological extrahepatic syndromes and responds unsatisfactorily to immunosuppressive drugs. Ursodeoxycholic acid leads to biochemical and possibly histological benefits. In contrast, PSC affects younger men who suffer from inflammatory bowel disease in 75% of cases. PSC is not characterized by specific serum autoantibodies. The diagnosis is reached by histology and typical findings upon cholangiography. In 10-20% PSC is associated with cholangiocarcinoma and also with colon cancer. PSC also does not respond well to immunosuppression. Therapeutic interventions include mechanical endoscopic manipulation of the bile ducts, treatment of cholangitis and ursodeoxycholic acid. AIH is a classical autoimmune disease with a female predisposition, circulating autoantibodies, elevated immunoglobulins, the association of other extrahepatic autoimmune diseases, and a dramatic response to immunosuppression with normalization of the patient's prognosis upon remission and prevention of cirrhosis. However, the diagnosis is only reached by the exclusion of other liver diseases also characterized by biochemical, histological and clinical features of chronic hepatitis. In this light, the precise diagnosis is essential. In spite of the clear distinctions of the three diseases overlapping syndromes do exist. These can be characterized as the coexistence of serological parameters of PBC and AIH, of cholestasis and hepatitis, of autoantibodies and viral markers, or the consecutive manifestation of PBC and AIH, or AIH and PSC. However, the overlap of genuine autoimmune diseases is rare. This is relevant regarding therapy and must lead to the precise clinical and diagnostic discrimination of serological autoimmunity (autoantibodies) and genuine autoimmune disease (i.e. AIH) for the initiation of efficatious therapeutic measures. AIH, PBC and PSC are well established indications for liver transplantation with good results. Transplantation is required when cirrhosis is progressive despite therapy and is likely to lead to liver failure.
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PMID:[Autoimmune liver diseases and their overlap syndromes]. 1698 80

Chronic liver diseases that inevitably lead to hepatic fibrosis, cirrhosis and/or hepatocellular carcinoma have become a major cause of illness and death worldwide. Among them, cholangiopathies or cholestatic liver diseases comprise a large group of conditions in which injury is primarily focused on the biliary system. These include congenital diseases (such as biliary atresia and cystic fibrosis), acquired diseases (such as primary sclerosing cholangitis and primary biliary cirrhosis), and those that arise from secondary damage to the biliary tree from obstruction, cholangitis or ischaemia. These conditions are associated with a specific pattern of chronic liver injury centered on damaged bile ducts that drive the development of peribiliary fibrosis and, ultimately, biliary cirrhosis and liver failure. For most, there is no established medical therapy and, hence, these diseases remain one of the most important indications for liver transplantation. As a result, there is a major need to develop new therapies that can prevent the development of chronic biliary injury and fibrosis. This mini-review briefly discusses the pathophysiology of liver fibrosis and its progression to cirrhosis. We make a special emphasis on biliary fibrosis and current therapeutic options, such as angiotensin converting enzyme-2 (known as ACE2) over-expression in the diseased liver as a novel potential therapy to treat this condition.
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PMID:Current therapies and novel approaches for biliary diseases. 3062 32