Division of pediatric hepatology, mount sinai school of medicine, new york, ny, usa. The condition affects the liver, hindering or stopping the. Progressive familial intrahepatic cholestasis is a heterogeneous group of autosomal recessive liver disorders characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and endstage liver disease before adulthood. Cholestasis is a condition where bile cannot flow from the liver to the duodenum. Progressive familial intrahepatic cholestasis pfic, which is also referred to as bylers disease, bylers syndrome, or greenlandeskimo familial cholestasis, is an autosomal recessive inherited disease that disrupts the genes encoding protein transporters responsible for bile formation. Progressive familial intrahepatic cholestasis symptoms. Three types of progressive familial intrahepatic cholestasis pfic have been identified, but their etiologies include unknown mechanisms.
Progressive familial intrahepatic cholestasis type 3. Progressive familial intrahepatic cholestasis is a heterogeneous group of autosomal recessive liver disorders characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and endstage liver disease before adulthood alonso et al. Hyperbilirubinemia may be of prehepatic, intrahepatic, or posthepatic origin. In a general sense, pfic is an inherited disorder of childhood in which cholestasis of hepatocellular origin often presents in the neonatal period or the first year of life. Cholestasis, a term coined by hans pooper anatomic pathologist in 1956, is a. The clinical and biochemical findings are discussed and a clinical approach to determining the underlying etiology of cirrhosis is outlined. The mutations were identified by a combination of wholeexome sequencing and targeted sequencing of. Pfic4 in 12 patients from 8 families with progressive familial intrahepatic cholestasis4, sambrotta et al.
Pfic is an autosomal recessive liver disorder characterized by an intrahepatic cholestasis due to bile canalicular transport defects. It results from elevated bilirubin, starting at levels 2 mgdl. One of these is the progressive familial intrahepatic cholestasis pfic group of diseases. By convention, cholestasis is considered chronic if it lasts 6 months. Bile acid pool dynamics in progressive familial intrahepatic cholestasis with partial external bile diversion. Cholestasis, intrahepatic synonyms, cholestasis, intrahepatic pronunciation, cholestasis, intrahepatic translation, english dictionary definition of cholestasis, intrahepatic. Pdf colestasis intrahepatica familiar progresiva tipo 3. Colestasis intrahepatica familiar progresiva tipo 3.
Progressive familial intrahepatic cholestasis pfic is a rare inherited condition. Cholestasis, intrahepatic definition of cholestasis. Abcb4, cholestasis, progressive familial intrahepatic cholestasis. Hepatic cirrhosis is an important cause of morbidity and mortality. Cholestasis definition of cholestasis by the free dictionary. Progressive familial intrahepatic cholestasis type 2. Due to specific genetic mutations patients with pfic cannot properly transport bile out of their liver cells, leading to liver damage.
Jaundice and cholestasis knowledge for medical students. Extrahepatic cholestasis obstructive jaundice mechanical extrahepatic bile duct obstruction posthepatic jaundice etiology bile duct tumors cysts narrowing of the bile. Progressive familial intrahepatic cholestasis childrens. Extrahepatic cholestasis extrahepatic biliary obstruction. Liver transplantation and the management of progressive. Salih pekmezci iu cerrahpasa medical faculty department of general surgery definition. Disease cholestasis, progressive familial intrahepatic, 4 map to. Progressive familial intrahepatic cholestasis wikipedia.
Progressive familial intrahepatic cholestasis treatment. Cholestasis of pregnancy icp symptoms, causes, and. Jaundice, or icterus, refers to the yellowish discoloration of tissue caused by accumulated deposits of bilirubin. Progressive familial intrahepatic cholestasis pfic is a class of chronic cholestasis disorders that begin in infancy and usually progress to cirrhosis within the first decade of life. Cholestasis in children is caused by many different entities. The average age at onset is 3 months, although some patients do not develop jaundice until later, even as late as adolescence. Progressive familial intrahepatic cholestasis pfic is a heterogeneous group of liver disorders of autosomal recessive inheritance, characterized by an early onset of cholestasis usually during infancy with pruritus and malabsorption, which rapidly progresses and ends up as liver failure. Progressive familial intrahepatic cholestasis pfic, originally known as bylers disease, was first described in an amish kindred.
A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and endstage liver disease before adulthood. Whereas there is some overlap, the differential diagnosis is difrent from that of neonatal cholestasis and includes entitles such as choledochal cyst, sarcoma botryoides of the extrahepatic bile ducts,2 hypoplasia of the bile ducts,3 drugs e. Pfic3 progressive familial intrahepatic cholestasis type 3 is an inherited cholestatic disorder caused by mutations in the abcb4 gene encoding the multidrug resistance protein 3 mdr3 protein. Description cholestasis is caused by obstruction within the liver. Progressive familial intrahepatic cholestasis type 2 pfic2 is a rare condition that affects the liver. Progressive familial intrahepatic cholestasis pfic is a group of inherited cholestatic conditions that develop as a result of impaired bile secretion. The two basic distinctions are an obstructive type of cholestasis where there is a mechanical blockage in the duct system that can occur from a gallstone or malignancy, and metabolic types of cholestasis which are disturbances in bile formation that can occur because of genetic defects or acquired.
Colestasis intrahepatica familiar progresiva orphanet. Colestasis intrahepatica familiar progresiva tipo 2 orphanet. Jericho hs, kaurs e, boverhof r, knisely a, shneider bl, verkade hj, whitington pf j pediatr gastroenterol nutr 2015 mar. Pressure on the bile ducts due to a nearby mass or tumor. Bilirubin deposition most commonly occurs in the skin and the sclerae. Progressive familial intrahepatic cholestasis genetics. At least three different genetic defects cause varieties of the disease. This usually leads to failure to thrive, cirrhosis, and the need for liver transplantation.
Progressive familial intrahepatic cholestasis pfic is a group of familial cholestatic conditions caused by defects in biliary epithelial transporters. An unusual case of cirrhosis and portal hypertension in an 18yearold patient secondary to progressive intrahepatic cholestasis is discussed. Progressive familial intrahepatic cholestasis intechopen. Cholestasis, progressive familial intrahepatic, 2 concept. The condition has an early onset and usually leads to endstage liver disease by the end of the second decade. It is subdivided into three types with slightly different clinical, biochemical and histological features.
Cholestasis, progressive familial intrahepatic 3 symptoms. The term is taken from the greek chole, bile, and stasis, standing still. Progressive familial intrahepatic cholestasis pfic is a rare genetic disorder that affects the liver. Progressive familial intrahepatic cholestasis pfic is a disorder that causes progressive liver disease, which typically leads to liver failure. Being fed exclusively through a vein iv primary biliary cirrhosis. Canalicular cholestasis can be produced by drugschemicals that damage the bile canalicular structures. Disorders of the liver, bile duct, or pancreas can cause cholestasis. Progressive familial intrahepatic cholestasis pfic is a heterogeneous group of rare, autosomal recessive disorders resulting from defects in the atp8b1 pfic1, abcb11 pfic2, abcb4 pfic3, or tjp2 pfic4 genes that lead to abnormal bile formation and elevated serum bile acids. Cholestasis is any condition in which the flow of bile from the liver is blocked. This leads to a buildup of bile inside the liver cell, known as cholestasis. Cholestasis may be transient or chronic treinenmoslen, 2001 and may be subdivided into canalicular cholestasis and cholangiodestructive cholestasis.
It manifests in infancy or childhood and can progress to failure to thrive or even advanced liver disease. Epidemiology the incidence of icp is higher in south america and scandinavia, but the highest rate was detecting in chile 16%. Progressive familial intrahepatic cholestasis web group. In people with pfic, liver cells are less able to secrete a digestive fluid called bile. People with this condition generally develop signs and symptoms during infancy, which may include severe itching, jaundice, failure to thrive, portal hypertension high blood pressure in the vein that provides blood to the liver and hepatosplenomegaly. In recent years it was found that patients with pfic have mutations in three genes, atp8b1, abcb11 and abcb4. A4250 for progressive familial intrahepatic cholestasis nihrio hsric id. A4250 for progressive familial intrahepatic cholestasis. Mutations in the atp8b1 gene cause two autosomal recessive disorders affecting liver. Definition cholestasis is a condition caused by rapidly developing acute or longterm chronic interruption in the excretion of bile a digestive fluid that helps the body process fat. Cholestasis may also be related to mixed mechanisms in diseases such as lymphoma 1.
Progressive familial intrahepatic cholestasis pfic is a group of rare disorders which are caused by defect in bile secretion and present with intrahepatic cholestasis, usually in infancy and. The skin and whites of the eyes look yellow, the skin itches, urine is dark, and stools may become lightcolored and smell foul. Progressive familial intrahepatic cholestasis pfic. Progressive familial intrahepatic cholestasis mayo clinic. Combines pdf files, views them in a browser and downloads. Progressive familial intrahepatic cholestasis definition. The buildup of bile in liver cells causes liver disease in affected individuals. Intrahepatic cholestasis of pregnancy is a condition in which the normal flow of bile is affected by the increased amounts of pregnancy hormones cholestasis is more common in the last trimester of pregnancy when hormones are at their peak cholestasis occurs in about 1 out of 1,000 pregnancies but is more common in swedish and chilean ethnic groups. Intrahepatic cholestasis may result from hepatocellular functional defects or from obstructive lesions of the intrahepatic biliary tract distal from bile canaliculi.
Progressive familial intrahepatic cholestasis pfic is the name given to a group of conditions in which liver cells do not release a digestive fluid, called bile, properly. Pfic is an autosomal recessive liver disorder characterized by an intrahepatic cholestasis due to bile. A rare inherited condition where bile is unable to drain from the liver where it builds up and causes progressive liver damage. Extrahepatic cholestasis accounts for 70% of all cholestasis cases. The clinical presentation usually occurs first in childhood with progressive cholestasis. The differential diagnosis of intra and extrahepatic. Genetic heterogeneity of progressive familial intrahepatic cholestasis. Ramaiah, atrayee banerjee, in handbook of toxicology of chemical warfare agents, 2009.
1231 1322 1129 890 642 1018 981 1199 1460 1490 264 697 1528 880 1408 688 252 1338 889 1155 688 817 1069 556 1439 1123 611 256 1371 864 1538 981 1346 1158 891 845 940 303 368 209 1294 1076 1072