Primary sclerosing cholangitis
Encyclopedia
Primary sclerosing cholangitis (PSC) is a chronic liver disease
caused by progressive inflammation
and scarring of the bile duct
s of the liver. The inflammation impedes the flow of bile
to the gut, which can ultimately lead to liver cirrhosis
, liver failure
and liver cancer
. The underlying cause of the inflammation is believed to be autoimmunity
; and more than 80% of those with PSC have ulcerative colitis. The definitive treatment is liver transplantation
.
of the bile duct, usually in the setting of endoscopic retrograde cholangiopancreatography
(ERCP, endoscopy
of the bile duct and pancreas
), which shows "beading" (both strictures and dilation) of the intrahepatic and extrahepatic bile ducts. Another option is magnetic resonance cholangiopancreatography
(MRCP), where magnetic resonance imaging
is used to visualise the biliary tract.
Most patients with PSC have evidence of autoantibodies. Approximately 80% of patients have perinuclear anti-neutrophil cytoplasmic antibodies, also called p-ANCA; however, this finding is not specific for PSC. Antinuclear antibodies and anti-smooth muscle antibody
are found in 20%-50% of PSC patients and, likewise, are not specific for the disease.
Other tests often done are a full blood count, liver enzymes, bilirubin
levels (usually grossly elevated), renal function
, electrolyte
s. Fecal fat
determination is occasionally ordered when the symptoms of malabsorption are prominent.
The differential diagnosis can include primary biliary cirrhosis
, drug induced cholestasis
, cholangiocarcinoma
, and HIV
-associated cholangiopathy.
. There is an increased prevalence of HLA
alleles A1, B8, and DR3 in primary sclerosing cholangitis.
. Bile stasis and back-pressure induces proliferation of epithelial cells and focal destruction of the liver parenchyma, forming bile lakes. Chronic biliary obstruction causes portal tract fibrosis and ultimately biliary cirrhosis and liver failure.
Bile assists in the enteric breakdown and absorption of fat; the absence of bile leads to fat malabsorption and deficiencies of fat-soluble vitamins (A, D, E, K).
can be active for a long time before it is noticed or diagnosed. There is relatively little data on the prevalence and incidence of primary sclerosing cholangitis, with studies in different countries showing annual incidence of 0.068–1.3 per 100,000 people and prevalence 0.22–8.5 per 100,000; given that PSC is closely linked with ulcerative colitis, it is likely that the risk is higher in populations where UC is more common.
, a cancer of the biliary tree, and the lifetime risk for PSC sufferers is 10-15%. Screening for cholangiocarcinoma in patients with primary sclerosing cholangitis is encouraged, but there is no general consensus on the modality and interval of choice.
Colon cancer is also associated with PSC.
PSC has a significant association with ulcerative colitis
, an inflammatory bowel disease
primarily affecting the large intestine. As many as 5% of patients with ulcerative colitis may progress to develop primary sclerosing cholangitis and approximately 70% of people with primary sclerosing cholangitis have ulcerative colitis.
, a bile acid naturally produced by the liver, which has been shown to lower elevated liver enzyme numbers in people with PSC, but has not improved liver- or overall survival. Treatment also includes medication to relieve itching (antipruritic
s), bile acid sequestrant
s (cholestyramine
), antibiotic
s to treat infections, and vitamin
supplements, as people with PSC are often deficient in vitamin A
, vitamin D
, vitamin E
and vitamin K
.
In some cases, ERCP, which may involve stenting of the common bile duct, may be necessary in order to open major blockages (dominant strictures).
Liver transplantation
is the only proven long-term treatment of PSC. Indications for transplantation include recurrent bacterial cholangitis, jaundice refractory to medical and endoscopic treatment, decompensated cirrhosis and complications of portal hypertension
. In one series, 1, 2, and 5 year survival following liver transplantation for PSC was 90%, 86% and 85% respectively.
Liver disease
Liver disease is a broad term describing any single number of diseases affecting the liver.-Diseases:* Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons , autoimmunity or hereditary conditions...
caused by progressive inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
and scarring of the bile duct
Bile duct
A bile duct is any of a number of long tube-like structures that carry bile.Bile, required for the digestion of food, is excreted by the liver into passages that carry bile toward the hepatic duct, which joins with the cystic duct to form the common bile duct, which opens into the intestine.The...
s of the liver. The inflammation impedes the flow of bile
Bile
Bile or gall is a bitter-tasting, dark green to yellowish brown fluid, produced by the liver of most vertebrates, that aids the process of digestion of lipids in the small intestine. In many species, bile is stored in the gallbladder and upon eating is discharged into the duodenum...
to the gut, which can ultimately lead to liver cirrhosis
Cirrhosis
Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...
, liver failure
Liver failure
Acute liver failure is the appearance of severe complications rapidly after the first signs of liver disease , and indicates that the liver has sustained severe damage . The complications are hepatic encephalopathy and impaired protein synthesis...
and liver cancer
Liver cancer
Liver tumors or hepatic tumors are tumors or growths on or in the liver . Several distinct types of tumors can develop in the liver because the liver is made up of various cell types. These growths can be benign or malignant...
. The underlying cause of the inflammation is believed to be autoimmunity
Autoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...
; and more than 80% of those with PSC have ulcerative colitis. The definitive treatment is liver transplantation
Liver transplantation
Liver transplantation or hepatic transplantation is the replacement of a diseased liver with a healthy liver allograft. The most commonly used technique is orthotopic transplantation, in which the native liver is removed and replaced by the donor organ in the same anatomic location as the original...
.
Signs and symptoms
PSC is characterized by recurrent episodes of cholangitis, with progressive biliary scarring and obstruction.- Chronic fatigue (a non-specific symptom often present in liver disease)
- Severe jaundiceJaundiceJaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
with intense itchItchItch is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to classify it as any one type of sensory experience. Modern science has shown that itch has many similarities to pain, and while both are unpleasant sensory experiences, their behavioral response...
ing - MalabsorptionMalabsorptionMalabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...
(especially of fatFatFats consist of a wide group of compounds that are generally soluble in organic solvents and generally insoluble in water. Chemically, fats are triglycerides, triesters of glycerol and any of several fatty acids. Fats may be either solid or liquid at room temperature, depending on their structure...
) and steatorrheaSteatorrheaSteatorrhea is the presence of excess fat in feces. Stools may also float due to excess lipid, have an oily appearance and be especially foul-smelling. An oily anal leakage or some level of fecal incontinence may occur. There is increased fat excretion, which can be measured by determining the...
(fatty stool) due to biliary obstruction, leading to decreased levels of the fat-soluble vitaminVitaminA vitamin is an organic compound required as a nutrient in tiny amounts by an organism. In other words, an organic chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on...
s, AVitamin AVitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
, DVitamin DVitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
, EVitamin EVitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet. γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings...
and KVitamin KVitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
. - Signs of cirrhosisCirrhosisCirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...
- HepatomegalyHepatomegalyHepatomegaly is the condition of having an enlarged liver. It is a nonspecific medical sign having many causes, which can broadly be broken down into infection, direct toxicity, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdominal mass...
- Portal hypertension
- Ascending cholangitisAscending cholangitisAscending cholangitis or acute cholangitis is an infection of the bile duct , usually caused by bacteria ascending from its junction with the duodenum...
, or infectionInfectionAn infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
of the bile duct. - Dark urine due to excess conjugated bilirubin, which is water soluble, being excreted by the kidneys
- Hepatic encephalopathy
Diagnosis
The diagnosis is by imagingMedical imaging
Medical imaging is the technique and process used to create images of the human body for clinical purposes or medical science...
of the bile duct, usually in the setting of endoscopic retrograde cholangiopancreatography
Endoscopic retrograde cholangiopancreatography
Endoscopic retrograde cholangiopancreatography is a technique that combines the use of endoscopy and fluoroscopy to diagnose and treat certain problems of the biliary or pancreatic ductal systems...
(ERCP, endoscopy
Endoscopy
Endoscopy means looking inside and typically refers to looking inside the body for medical reasons using an endoscope , an instrument used to examine the interior of a hollow organ or cavity of the body. Unlike most other medical imaging devices, endoscopes are inserted directly into the organ...
of the bile duct and pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
), which shows "beading" (both strictures and dilation) of the intrahepatic and extrahepatic bile ducts. Another option is magnetic resonance cholangiopancreatography
Magnetic resonance cholangiopancreatography
Magnetic resonance cholangiopancreatography is a medical imaging technique that uses magnetic resonance imaging to visualise the biliary and pancreatic ducts in a non-invasive manner...
(MRCP), where magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
is used to visualise the biliary tract.
Most patients with PSC have evidence of autoantibodies. Approximately 80% of patients have perinuclear anti-neutrophil cytoplasmic antibodies, also called p-ANCA; however, this finding is not specific for PSC. Antinuclear antibodies and anti-smooth muscle antibody
Anti-smooth muscle antibody
Anti-smooth muscle antibodies are antibodies formed against smooth muscle. These antibodies are typically associated with autoimmune hepatitis.These antibodies can be directed against actin, troponin, and tropomyosin....
are found in 20%-50% of PSC patients and, likewise, are not specific for the disease.
Other tests often done are a full blood count, liver enzymes, bilirubin
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
levels (usually grossly elevated), renal function
Renal function
Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...
, electrolyte
Electrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....
s. Fecal fat
Fecal fat
In medicine, the fecal fat test is a diagnostic test for fat malabsorption conditions, which lead to excess fat in the feces .-Background:...
determination is occasionally ordered when the symptoms of malabsorption are prominent.
The differential diagnosis can include primary biliary cirrhosis
Primary biliary cirrhosis
Primary biliary cirrhosis, often abbreviated PBC, is an autoimmune disease of the liver marked by the slow progressive destruction of the small bile ducts within the liver. When these ducts are damaged, bile builds up in the liver and over time damages the tissue. This can lead to scarring,...
, drug induced cholestasis
Cholestasis
In medicine, cholestasis is a condition where bile cannot flow from the liver to the duodenum. The two basic distinctions are an obstructive type of cholestasis where there is a mechanical blockage in the duct system such as can occur from a gallstone or malignancy and metabolic types of...
, cholangiocarcinoma
Cholangiocarcinoma
Cholangiocarcinoma is a cancer of the bile ducts which drain bile from the liver into the small intestine. Other biliary tract cancers include pancreatic cancer, gallbladder cancer, and cancer of the ampulla of Vater...
, and HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
-associated cholangiopathy.
Etiology
The cause of PSC is unknown, although it is thought to be an autoimmune disorderAutoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...
. There is an increased prevalence of HLA
Human leukocyte antigen
The human leukocyte antigen system is the name of the major histocompatibility complex in humans. The super locus contains a large number of genes related to immune system function in humans. This group of genes resides on chromosome 6, and encodes cell-surface antigen-presenting proteins and...
alleles A1, B8, and DR3 in primary sclerosing cholangitis.
Pathophysiology
Inflammation damages bile ducts both inside and outside of the liver. The resulting scarring of the bile ducts blocks the flow of bile, causing cholestasisCholestasis
In medicine, cholestasis is a condition where bile cannot flow from the liver to the duodenum. The two basic distinctions are an obstructive type of cholestasis where there is a mechanical blockage in the duct system such as can occur from a gallstone or malignancy and metabolic types of...
. Bile stasis and back-pressure induces proliferation of epithelial cells and focal destruction of the liver parenchyma, forming bile lakes. Chronic biliary obstruction causes portal tract fibrosis and ultimately biliary cirrhosis and liver failure.
Bile assists in the enteric breakdown and absorption of fat; the absence of bile leads to fat malabsorption and deficiencies of fat-soluble vitamins (A, D, E, K).
Epidemiology
There is a 2:1 male-to-female predilection of primary sclerosing cholangitis. The disease normally starts from age 20 to 30, though may begin in childhood. PSC progresses slowly, so the diseaseDisease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
can be active for a long time before it is noticed or diagnosed. There is relatively little data on the prevalence and incidence of primary sclerosing cholangitis, with studies in different countries showing annual incidence of 0.068–1.3 per 100,000 people and prevalence 0.22–8.5 per 100,000; given that PSC is closely linked with ulcerative colitis, it is likely that the risk is higher in populations where UC is more common.
Related diseases
Primary sclerosing cholangitis is associated with cholangiocarcinomaCholangiocarcinoma
Cholangiocarcinoma is a cancer of the bile ducts which drain bile from the liver into the small intestine. Other biliary tract cancers include pancreatic cancer, gallbladder cancer, and cancer of the ampulla of Vater...
, a cancer of the biliary tree, and the lifetime risk for PSC sufferers is 10-15%. Screening for cholangiocarcinoma in patients with primary sclerosing cholangitis is encouraged, but there is no general consensus on the modality and interval of choice.
Colon cancer is also associated with PSC.
PSC has a significant association with ulcerative colitis
Ulcerative colitis
Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...
, an inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
primarily affecting the large intestine. As many as 5% of patients with ulcerative colitis may progress to develop primary sclerosing cholangitis and approximately 70% of people with primary sclerosing cholangitis have ulcerative colitis.
Therapy
Standard treatment includes ursodiolUrsodiol
Ursodiol, also known as ursodeoxycholic acid and the abbreviation UDCA, is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria.-Endogenous effects:...
, a bile acid naturally produced by the liver, which has been shown to lower elevated liver enzyme numbers in people with PSC, but has not improved liver- or overall survival. Treatment also includes medication to relieve itching (antipruritic
Antipruritic
Antipruritics, also known as anti-itch drugs, are medications that inhibit the itching that is often associated with sunburns, allergic reactions, eczema, psoriasis, chickenpox, fungal infections, insect bites and stings like those from mosquitoes, fleas, and mites, and contact dermatitis and...
s), bile acid sequestrant
Bile acid sequestrant
The bile acid sequestrants are a group of medications used to bind certain components of bile in the gastrointestinal tract. They disrupt the enterohepatic circulation of bile acids by sequestering them and preventing their reabsorption from the gut. In general, they are classified as hypolipidemic...
s (cholestyramine
Cholestyramine
Cholestyramine or colestyramine is a bile acid sequestrant, which binds bile in the gastrointestinal tract to prevent its reabsorption. It is a strong ion exchange resin, which means that it can exchange its chloride anions with anionic bile acids in the gastrointestinal tract and bind them...
), antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s to treat infections, and vitamin
Vitamin
A vitamin is an organic compound required as a nutrient in tiny amounts by an organism. In other words, an organic chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on...
supplements, as people with PSC are often deficient in vitamin A
Vitamin A
Vitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
, vitamin D
Vitamin D
Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
, vitamin E
Vitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet. γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings...
and vitamin K
Vitamin K
Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
.
In some cases, ERCP, which may involve stenting of the common bile duct, may be necessary in order to open major blockages (dominant strictures).
Liver transplantation
Liver transplantation
Liver transplantation or hepatic transplantation is the replacement of a diseased liver with a healthy liver allograft. The most commonly used technique is orthotopic transplantation, in which the native liver is removed and replaced by the donor organ in the same anatomic location as the original...
is the only proven long-term treatment of PSC. Indications for transplantation include recurrent bacterial cholangitis, jaundice refractory to medical and endoscopic treatment, decompensated cirrhosis and complications of portal hypertension
Portal hypertension
In medicine, portal hypertension is hypertension in the portal vein and its tributaries.It is often defined as a portal pressure gradient of 10 mmHg or greater.-Causes:Causes can be divided into prehepatic, intrahepatic, and posthepatic...
. In one series, 1, 2, and 5 year survival following liver transplantation for PSC was 90%, 86% and 85% respectively.
Prognosis
A German study in 2007 estimated the average survival time from time of diagnosis to be approximately 25 years, and the median time until either death or liver transplantation to be approximately 10 years.See also
- BilirubinBilirubinBilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
- Child-Pugh scoreChild-Pugh scoreIn medicine , the Child-Pugh score is used to assess the prognosis of chronic liver disease, mainly cirrhosis...
- CholangiocarcinomaCholangiocarcinomaCholangiocarcinoma is a cancer of the bile ducts which drain bile from the liver into the small intestine. Other biliary tract cancers include pancreatic cancer, gallbladder cancer, and cancer of the ampulla of Vater...
- Liver function testsLiver function testsLiver function tests , are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver. The parameters measured include PT/INR, aPTT, albumin, billirubin and others...
- Primary biliary cirrhosisPrimary biliary cirrhosisPrimary biliary cirrhosis, often abbreviated PBC, is an autoimmune disease of the liver marked by the slow progressive destruction of the small bile ducts within the liver. When these ducts are damaged, bile builds up in the liver and over time damages the tissue. This can lead to scarring,...
- Alagille syndromeAlagille syndromeAlagille syndrome is a genetic disorder that affects the liver, heart, kidney, and other systems of the body. Problems associated with the disorder generally become evident in infancy or early childhood...
- Progressive familial intrahepatic cholestasisProgressive familial intrahepatic cholestasisProgressive familial intrahepatic cholestasis refers to a group of familial cholestatic conditions caused by defects in biliary epithelial transporters. The clinical presentation usually occurs first in childhood with progressive cholestasis...
- Walter PaytonWalter PaytonWalter Jerry Payton was an American football running back who played for the Chicago Bears of the National Football League for thirteen seasons. Walter Payton was known around the NFL as "Sweetness". He is remembered as one of the most prolific running backs in the history of American football...
(died of primary sclerosing cholangitis) - Chris LeDouxChris LeDouxChris Ledoux was an American country music singer-songwriter, bronze sculptor and rodeo champion.During his career LeDoux recorded 36 albums which have sold more than six million units in the United States as of January 2007...
(professional rodeo rider and country musician with PSC who died of cholangiocarcinomaCholangiocarcinomaCholangiocarcinoma is a cancer of the bile ducts which drain bile from the liver into the small intestine. Other biliary tract cancers include pancreatic cancer, gallbladder cancer, and cancer of the ampulla of Vater...
) - Chris KlugChris KlugChris Klug is a professional alpine snowboarder. After receiving a liver transplant in 2000 to treat Primary sclerosing cholangitis, he went on to compete in the 2002 Winter Olympics in Salt Lake City. This was the first and so far only time a transplantee had competed in the Olympics, either...
(professional snowboarder with PSC who had liver transplant)
External links
- PSC Partners: Patient organization with additional information
- PSC Support : UK based Patient organization with additional information and discussion forum
- Additional Literature about PSC
- Information from The Morgan Foundation for the Study of PSC