Therefore, it is hypothesized that a reduction in secondary bile acid production, as a result of dysbiosis, could lead to bile duct damage via decreased activation of FXR and TGR5. Indeed, lower levels of secondary bile acids were found in PSC patients, but a causal relationship is yet to be confirmed. Familial intrahepatic cholestasis
Familial intrahepatic cholestasis (FIH) is a group of disorders that lead to intrahepatic cholestasis in children. Most often, FIH occurs during the first year of life, with an incidence rate of 1/50,000 to 1/100,000. There are three different versions of FIH, with each causing a different severity of jaundice. Typically, children exhibit recurrent jaundice episodes, which eventually become permanent. Diagnosis usually occurs by analyzing laboratory features, liver biopsy results, DNA/RNA sequences, and biliary lipid analysis. The definitive treatment for FIH is liver transplant which usually results in a high recovery rate. Each type of FIH is a result of a different mutation. The three genes thought to be involved include APT8B1, which encodes for the FIC1 protein. The ABCB11 gene encodes for the bile salt export pump (BSEP) protein, and the ABCB4 gene encodes for the multidrug resistance 3 (MDR3) protein. BSEP and MDR3 are respectively responsible for transporting bile salt and phospholipid, two major constituents of bile, across the apical membrane of hepatocytes. Alagille syndrome
Alagille syndrome is an autosomal dominant disorder that impacts five systems, including the liver, heart, skeleton, face, and eyes.
An exostosis, also known as bone spur, is the formation of new bone on the surface of a bone. Exostoses can cause chronic pain ranging from mild to debilitatingly severe, depending on the shape, size, and location of the lesion. It is most commonly found in places like the ribs, where small bone growths form, but sometimes larger growths can grow on places like the ankles, knees, shoulders, elbows and hips. Very rarely are they on the skull. Exostoses are sometimes shaped like spurs, such as calcaneal spurs. Osteomyelitis, a bone infection, may leave the adjacent bone with exostosis formation. Charcot foot, the neuropathic breakdown of the feet seen primarily in diabetics, can also leave bone spurs that may then become symptomatic. They normally form on the bones of joints, and can grow upwards. For example, if an extra bone formed on the ankle, it might grow up to the shin. When used in the phrases "cartilaginous exostosis" or "osteocartilaginous exostosis", the term is considered synonymous with osteochondroma. Some sources consider the two terms to mean the same thing even without qualifiers, but this interpretation is not universal. Osteophytes
Osteophytes are bone spurs that develop on the margins of joints secondary to external stimuli such as osteoarthritis. However, these are not always distinguished from exostoses in any definite way. Fossil record
Evidence for exostosis found in the fossil record is studied by paleopathologists, specialists in ancient disease and injury.