Primary sclerosing cholangitis (PSC) is a long-term progressive disease of the
liver
The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
and
gallbladder
In vertebrates, the gallbladder, also known as the cholecyst, is a small hollow Organ (anatomy), organ where bile is stored and concentrated before it is released into the small intestine. In humans, the pear-shaped gallbladder lies beneath t ...
characterized by
inflammation
Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
and scarring of the
bile duct
A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates. The bile duct is separated into three main parts: the fundus (superior), the body (middle), and the neck (inferior).
Bile is requ ...
s, which normally allow
bile
Bile (from Latin ''bilis''), also known as gall, is a yellow-green/misty green fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is primarily composed of water, is pro ...
to drain from the gallbladder. Affected individuals may have no symptoms or may experience signs and symptoms of liver disease, such as
jaundice
Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...
,
itching
An itch (also known as pruritus) is a sensation that causes a strong desire or reflex to scratch. Itches have resisted many attempts to be classified as any one type of sensory experience. Itches have many similarities to pain, and while both ...
, and abdominal pain.
The bile duct scarring that occurs in PSC narrows the ducts of the
biliary tree
The biliary tract (also biliary tree or biliary system) refers to the liver, gallbladder and bile ducts, and how they work together to make, store and secrete bile. Bile consists of water, electrolytes, bile acids, cholesterol, phospholipids a ...
and impedes the flow of bile to the
duodenum
The duodenum is the first section of the small intestine in most vertebrates, including mammals, reptiles, and birds. In mammals, it may be the principal site for iron absorption.
The duodenum precedes the jejunum and ileum and is the shortest p ...
. Eventually, it can lead to
cirrhosis
Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...
of the liver and
liver failure
Liver failure is the inability of the liver to perform its normal synthetic and metabolic functions as part of normal physiology. Two forms are recognised, acute and chronic (cirrhosis). Recently, a third form of liver failure known as acute- ...
. PSC increases the risk of various cancers, including
liver cancer
Liver cancer, also known as hepatic cancer, primary hepatic cancer, or primary hepatic malignancy, is cancer that starts in the liver. Liver cancer can be primary in which the cancer starts in the liver, or it can be liver metastasis, or secondar ...
,
gallbladder carcinoma,
colorectal cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the Colon (anatomy), colon or rectum (parts of the large intestine). Signs and symptoms may include Lower gastrointestinal ...
, and
cholangiocarcinoma
Cholangiocarcinoma, also known as bile duct cancer, is a type of cancer that forms in the bile ducts. Symptoms of cholangiocarcinoma may include abdominal pain, yellowish skin, weight loss, generalized itching, and fever. Light colored stoo ...
.
The underlying cause of PSC is unknown. Genetic susceptibility,
immune system dysfunction, and
abnormal composition of the gut flora may play a role.
This is further suggested by the observation that around 75% of individuals with PSC also have
inflammatory bowel disease
Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, with Crohn's disease and ulcerative colitis (UC) being the principal types. Crohn's disease affects the small intestine and large intestine ...
(IBD), most often
ulcerative colitis
Ulcerative colitis (UC) is one of the two types of inflammatory bowel disease (IBD), with the other type being Crohn's disease. It is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary sympto ...
.
No effective medical treatment for primary sclerosing cholangitis is known. Its most definitive treatment is a
liver transplant
Liver transplantation or hepatic transplantation is the replacement of a Liver disease, diseased liver with the healthy liver from another person (allograft). Liver transplantation is a treatment option for Cirrhosis, end-stage liver disease and ...
,
but disease recurrence can occur in 25–30% of cases.
For patients unable or unwilling to receive a transplant, therapy primarily focuses on relieving symptoms, rather than stopping disease progression. If the sclerosing cholangitis is a ''secondary'' effect of a different disease, treatment is directed towards the underlying cause.
PSC is a rare disease and most commonly affects people with IBD.
About 3.0 to 7.5% of people with ulcerative colitis have PSC, and 80% of people with PSC have some form of IBD.
Diagnosis usually occurs in people in their 30s or 40s.
Individuals of Northern European ancestry are affected more often than people of Southern European or Asian descent.
Men are affected more often than women.
The disease was initially described in the mid-1800s, but was not fully characterized until the 1970s with the advent of improved medical-imaging techniques such as
endoscopic retrograde cholangiopancreatography
Endoscopic retrograde cholangiopancreatography (ERCP) is a technique that combines the use of endoscopy
An endoscopy is a procedure used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior ...
.
Signs and symptoms
Nearly half of people with PSC do not have symptoms, and are often incidentally discovered to have PSC due to abnormal
liver function tests
Liver function tests (LFTs or LFs), also referred to as a hepatic panel or liver panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial ...
;
however, a substantial proportion have debilitating signs and symptoms of the disease.
Signs and symptoms of PSC may include severe
itching
An itch (also known as pruritus) is a sensation that causes a strong desire or reflex to scratch. Itches have resisted many attempts to be classified as any one type of sensory experience. Itches have many similarities to pain, and while both ...
and nonspecific fatigue.
Jaundice
Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...
may also be seen. Enlargement of the
liver
The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
and
spleen
The spleen (, from Ancient Greek '' σπλήν'', splḗn) is an organ (biology), organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter.
The spleen plays important roles in reg ...
are seen in roughly 40% of affected individuals. Abdominal pain affects about 20% of people with PSC.
Multiple episodes of life-threatening acute
cholangitis (infection within the bile ducts) can be seen due to impaired drainage of the bile ducts, which increases the risk of infection.
* Dark urine due to excess
conjugated bilirubin
Bilirubin (BR) (adopted from German, originally bili—bile—plus ruber—red—from Latin) is a red-orange compound that occurs in the normcomponent of the straw-yellow color in urine. Another breakdown product, stercobilin, causes the brown ...
, which is water-soluble and excreted by the kidneys (i.e. choluria)
*
Malabsorption
Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a varie ...
, especially of
fat
In nutrition science, nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such chemical compound, compounds, most commonly those that occur in living beings or in food.
The term often refers specif ...
, and
steatorrhea
Steatorrhea (or steatorrhoea) is the presence of excess fat in Human feces, feces. Stools may be bulky and difficult to flush, have a pale and oily appearance, and can be especially foul-smelling. An oily anal leakage or some level of fecal incon ...
(fatty stool), due to an inadequate amount of bile reaching the small intestine, leading to decreased levels of the fat-soluble
vitamin
Vitamins are Organic compound, organic molecules (or a set of closely related molecules called vitamer, vitamers) that are essential to an organism in small quantities for proper metabolism, metabolic function. Nutrient#Essential nutrients, ...
s,
A,
D,
E, and
K.
*
Portal hypertension
Portal hypertension is defined as increased portal venous pressure, with a hepatic venous pressure gradient greater than 5 mmHg. Normal portal pressure is 1–4 mmHg; clinically insignificant portal hypertension is present at portal pressures 5� ...
, a complication of
cirrhosis
Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...
, which can manifest with
esophageal and parastomal varices as well as
hepatic encephalopathy
Hepatic encephalopathy (HE) is an altered level of consciousness as a result of liver failure. Its onset may be gradual or sudden. Other symptoms may include movement problems, changes in mood, or changes in personality. In the advanced stag ...
(mental status alteration/disturbance caused by liver dysfunction and shunting of blood away from the scarred liver; such that ammonia detoxification is reduced with concomitant encephalopathy) or
ascites
Ascites (; , meaning "bag" or "sac") is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdo ...
.
Cause
The exact cause of primary sclerosing cholangitis is unknown, and its pathogenesis is improperly understood.
Although PSC is thought to be caused by
autoimmune disease
An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It is estimated tha ...
, it does not demonstrate a clear response to immunosuppressants. Thus, many experts believe it to be a complex, multifactorial (including immune-mediated) disorder and perhaps one that encompasses several different hepatobiliary diseases.
Alternatively, some experts have suggested that the reason immunosuppressant medications are ineffective is because PSC almost always remains undiagnosed until a very advanced stage, at which point damage may be irreversible or require more aggressive treatment than other autoimmune diseases.
Data have provided novel insights suggesting:
# an important association between the intestinal
microbiota
Microbiota are the range of microorganisms that may be commensal, mutualistic, or pathogenic found in and on all multicellular organisms, including plants. Microbiota include bacteria, archaea, protists, fungi, and viruses, and have been found ...
and PSC and
# a process referred to as
cellular senescence
Cellular senescence is a phenomenon characterized by the cessation of cell division. In their experiments during the early 1960s, Leonard Hayflick and Paul Moorhead found that normal human fetal fibroblasts in culture reach a maximum of appro ...
and the senescence-associated secretory phenotype in the pathogenesis of PSC.
In addition, longstanding, well-recognized associations are seen between PSC and
human leukocyte antigen
The human leukocyte antigen (HLA) system is a complex of genes on chromosome 6 in humans that encode cell-surface proteins responsible for regulation of the immune system. The HLA system is also known as the human version of the major histo ...
alleles (A1, B8, and DR3).
[
]
Pathophysiology
PSC is characterized by inflammation of the bile ducts (cholangitis) with consequent stricturing (i.e., narrowing) and hardening ( sclerosis) of these ducts due to scar formation, be it inside and/or outside the liver. The resulting scarring of the bile ducts obstructs the flow of bile, which further perpetuates bile duct and liver injury. Chronic impairment of bile flow due to blockage and dysfunctional bile transport (cholestasis
Cholestasis is a condition where the flow of bile from the liver to the duodenum is impaired. The two basic distinctions are:
* obstructive type of cholestasis, where there is a mechanical blockage in the duct system that can occur from a gallston ...
) causes progressive biliary fibrosis and ultimately biliary cirrhosis and liver failure.
The primary physiological function of bile is to assist in the breakdown and absorption of fat in the intestinal tract; a relative deficiency of bile can lead to fat malabsorption and deficiencies of fat-soluble vitamins (A, D, E, K).
Liver enlargement is seen due to portal hypertension caused by compression of portal vein
The portal vein or hepatic portal vein (HPV) is a blood vessel that carries blood from the gastrointestinal tract, gallbladder, pancreas and spleen to the liver. This blood contains nutrients and toxins extracted from digested contents. Approxima ...
s by the proximate sclerosed intrahepatic bile ducts, and leads to right upper quadrant abdominal pain.
Diagnosis
PSC is generally diagnosed on the basis of having at least two of three clinical criteria after secondary causes of sclerosing cholangitis have been ruled out:
* serum alkaline phosphatase
The enzyme alkaline phosphatase (ALP, alkaline phenyl phosphatase, also abbreviated PhoA) is a phosphatase with the physiological role of dephosphorylating compounds. The enzyme is found across a multitude of organisms, prokaryotes and eukaryo ...
(ALP) > 1.5x the upper limit of normal for longer than 6 months
* cholangiography demonstrating biliary strictures or irregularity consistent with PSC
* liver biopsy consistent with PSC (if available)
Historically, a cholangiogram would be obtained via endoscopic retrograde cholangiopancreatography
Endoscopic retrograde cholangiopancreatography (ERCP) is a technique that combines the use of endoscopy
An endoscopy is a procedure used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior ...
(ERCP), which typically reveals "beading" (alternating strictures and dilation) of the bile ducts inside and/or outside the liver. Currently, the preferred option for diagnostic cholangiography, given its noninvasive yet highly accurate nature, is magnetic resonance cholangiopancreatography (MRCP), a magnetic resonance imaging
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and ...
technique. MRCP has unique strengths, including high spatial resolution, and can even be used to visualize the biliary tract
The biliary tract (also biliary tree or biliary system) refers to the liver, gallbladder and bile ducts, and how they work together to make, store and secrete bile. Bile consists of water, electrolytes, bile acids, cholesterol, phospholipids an ...
of small animal models of PSC.
Most people with PSC have evidence of autoantibodies
An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies.
Pr ...
and abnormal immunoglobulin levels. For example, approximately 80% of people with PSC have perinuclear antineutrophil cytoplasmic antibodies (P-ANCA); however, this and other immunoglobulin findings are not specific to those with PSC and are of unclear clinical significance/consequence. Antinuclear antibodies and anti-smooth muscle antibody are found in 20–50% of PSC patients, and likewise are not specific for the disease, but may identify a subgroup of PSC patients who also have autoimmune hepatitis (i.e. PSC-AIH overlap syndrome).[
The differential diagnosis can include primary biliary cholangitis (formerly referred to as ]primary biliary cirrhosis
Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune disease of the liver. It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to buil ...
), drug-induced cholestasis
Cholestasis is a condition where the flow of bile from the liver to the duodenum is impaired. The two basic distinctions are:
* obstructive type of cholestasis, where there is a mechanical blockage in the duct system that can occur from a gallston ...
, cholangiocarcinoma
Cholangiocarcinoma, also known as bile duct cancer, is a type of cancer that forms in the bile ducts. Symptoms of cholangiocarcinoma may include abdominal pain, yellowish skin, weight loss, generalized itching, and fever. Light colored stoo ...
, IgG4-related disease, post-liver transplantation nonanastomotic biliary strictures, and HIV
The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the im ...
-associated cholangiopathy. Primary sclerosing cholangitis and primary biliary cholangitis are distinct entities and exhibit important differences, including the site of tissue damage within the liver, associations with IBD, which includes ulcerative colitis and Crohn's disease, response to treatment, and risks of disease progression.
Classification
Primary sclerosing cholangitis is typically classified into three subgroups based on whether the small and/or large bile ducts are affected. The subgroups of PSC include:
* Classic PSC
* Small-duct PSC
* PSC associated with autoimmune hepatitis
Autoimmune hepatitis, formerly known as lupoid hepatitis, plasma cell hepatitis, or autoimmune chronic active hepatitis, is a chronic, autoimmune disease of the liver that occurs when the body's immune system attacks liver cells, causing the liv ...
Management
No pharmacologic treatment has been approved by the U.S. Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
for PSC. Some experts recommend a trial of ursodeoxycholic acid
Ursodeoxycholic acid (UDCA), also known as ursodiol, is a secondary bile acid, produced in humans and most other species from metabolism by intestinal bacteria. It is synthesized in the liver in some species, and was first identified in bile o ...
(UDCA), a bile acid occurring naturally in small quantities in humans, as it has been shown to lower elevated liver enzyme numbers in patients with PSC and has proven effective in other cholestatic liver diseases. However, UDCA has yet to be shown to clearly lead to improved liver histology and survival. Guidelines from the American Association for the Study of Liver Diseases and the American College of Gastroenterology
The American College of Gastroenterology (ACG) is a Bethesda, Maryland–based medical association of gastroenterologists.
The association was founded in 1932 and holds annual meetings and regional postgraduate continuing education courses, est ...
do not support the use of UDCA but guidelines from the European Association for the Study of the Liver do endorse the use of moderate doses (13–15 milligrams per kilogram) of UDCA for PSC.
Supportive treatment for PSC symptoms is the cornerstone of management. These therapies are aimed at relieving symptoms such as itching with antipruritic
Antipruritics, abirritants, or anti-itch drugs, are medications that inhibit itching (Latin: ''pruritus'').
Itching is often associated with sunburns, allergic reactions, eczema, psoriasis, chickenpox, Fungal infection in animals, fungal infections ...
s (e.g. bile acid sequestrant
The bile acid sequestrants are a group of resins used to bind certain components of bile in the gastrointestinal tract. They disrupt the enterohepatic circulation of bile acids by combining with bile constituents and preventing their reabsorption f ...
s such as cholestyramine
Colestyramine ( INN) or cholestyramine ( USAN) (trade names Questran, Questran Light, Cholybar, Olestyr, Quantalan, Vasosan) is a bile acid sequestrant, which binds bile in the gastrointestinal tract to prevent its reabsorption. It is a strong i ...
); antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
s to treat episodes of ascending cholangitis
Ascending cholangitis, also known as acute cholangitis or simply cholangitis, is inflammation of the bile duct, usually caused by bacteria ascending from Ampulla of Vater, its junction with the duodenum (first part of the small intestine). It ten ...
; and vitamin supplements, as people with PSC are often deficient in fat-soluble vitamins (A, D, E, and K).
ERCP and specialized techniques may also be needed to help distinguish between a benign PSC stricture and a bile-duct cancer (cholangiocarcinoma).
Liver transplantation is the only proven long-term treatment of PSC. Indications for transplantation include recurrent bacterial ascending cholangitis, decompensated cirrhosis, hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide.
HCC most common ...
, hilar cholangiocarcinoma, and complications of portal hypertension. Not all patients are candidates for liver transplantation, and some experience disease recurrence afterward. The reasons why some patients develop recurrent PSC remains largely obscure, but surprisingly, those without recurrence of disease (hence protected from recurrence) are characterized by an increased presence of the potentially pathogenic '' Shigella
''Shigella'' is a genus of bacteria that is Gram negative, facultatively anaerobic, non–spore-forming, nonmotile, rod shaped, and is genetically nested within ''Escherichia''. The genus is named after Kiyoshi Shiga, who discovered it in 1 ...
'' species.
Complications
Cholangiocarcinoma
Cholangiocarcinoma, also known as bile duct cancer, is a type of cancer that forms in the bile ducts. Symptoms of cholangiocarcinoma may include abdominal pain, yellowish skin, weight loss, generalized itching, and fever. Light colored stoo ...
(CCA) represents a major complication and the leading cause of death in patients with primary sclerosing cholangitis (PSC), with a lifetime prevalence ranging from 6-13%. Patients with PSC have a 400-600 fold higher risk of developing CCA compared to the general population, with an annual risk between 0.5-1.5%. Notably, 30-50% of PSC-associated CCAs are diagnosed within the first year after PSC diagnosis, and up to 80% of patients die within one year of CCA detection. Risk factors include advanced age, male sex, concomitant inflammatory bowel disease, and high-grade biliary strictures. The development of CCA follows a multistep carcinogenesis
Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cell (biology), cells are malignant transformation, transformed into cancer cells. The process is characterized by changes at the cellular, G ...
model involving chronic inflammation, which progresses from damaged biliary epithelium to dysplasia and eventually invasive cancer, with molecular mechanisms including inflammatory pathways, oxidative stress, genetic alterations (commonly affecting p53
p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...
), and epigenetic
In biology, epigenetics is the study of changes in gene expression that happen without changes to the DNA sequence. The Greek prefix ''epi-'' (ἐπι- "over, outside of, around") in ''epigenetics'' implies features that are "on top of" or "in ...
changes that create an aberrant phenotype in cholangiocytes.
Prognosis
There are no reliable prognostic models for PSC, owing to the highly variable disease course. Patients who are asymptomatic at the time of diagnosis are known to have better outcomes than those who have symptoms. However, many asymptomatic patients will develop symptoms later in time. Laboratory tests such as liver function tests
Liver function tests (LFTs or LFs), also referred to as a hepatic panel or liver panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial ...
are surprisingly unreliable when used as prognostic indicators for PSC.
Estimated median survival from diagnosis until liver transplant or PSC-related death is 21.3 years. Various models have been developed to help predict survival, but their use is generally best suited for research and not clinical purposes. A serum alkaline phosphatase
The enzyme alkaline phosphatase (ALP, alkaline phenyl phosphatase, also abbreviated PhoA) is a phosphatase with the physiological role of dephosphorylating compounds. The enzyme is found across a multitude of organisms, prokaryotes and eukaryo ...
less than 1.5 times the upper limit of normal has been associated with better outcomes, but its use in predicting long-term outcomes is unclear. An IgA IGA or IgA may refer to:
Businesses and organizations
* IGA (supermarkets) (initially Independent Grocers Alliance), a name used by many independent supermarkets throughout the world
** IGA (Australian supermarket group), the local Australian v ...
isotype autoantibody
An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies.
Pr ...
to the pancreatic GP2 protein (anti-GP2 IgA antibody) is the first verified prognostic biomarker in PSC. The role of anti-GP2 IgA in PSC was simultaneously investigated and reported by two research groups, and later confirmed by others. Association was demonstrated between anti-GP2 IgA and progressive liver fibrosis, cholangiocarcinoma
Cholangiocarcinoma, also known as bile duct cancer, is a type of cancer that forms in the bile ducts. Symptoms of cholangiocarcinoma may include abdominal pain, yellowish skin, weight loss, generalized itching, and fever. Light colored stoo ...
development and shorter transplantation free survival in PSC patients.
Other markers which may be measured and monitored are a complete blood count
A complete blood count (CBC), also known as a full blood count (FBC) or full haemogram (FHG), is a set of medical laboratory tests that provide cytometry, information about the cells in a person's blood. The CBC indicates the counts of white blo ...
, serum liver enzymes, bilirubin
Bilirubin (BR) (adopted from German, originally bili—bile—plus ruber—red—from Latin) is a red-orange compound that occurs in the normcomponent of the straw-yellow color in urine. Another breakdown product, stercobilin, causes the brown ...
levels (usually grossly elevated), kidney function
Assessment of kidney function occurs in different ways, using the presence of symptoms and medical sign, signs, as well as measurements using urine tests, blood tests, and medical imaging.
Renal physiology, Functions of a healthy kidney include ...
, and electrolyte
An electrolyte is a substance that conducts electricity through the movement of ions, but not through the movement of electrons. This includes most soluble Salt (chemistry), salts, acids, and Base (chemistry), bases, dissolved in a polar solven ...
s. However, none of these tests are reliable indicators of prognosis, as they are either specific to certain disease complications or have a tendency to fluctuate over time, irrespective of the actual disease progression. Fecal fat measurement is occasionally ordered when symptoms of malabsorption (e.g., gross steatorrhea
Steatorrhea (or steatorrhoea) is the presence of excess fat in Human feces, feces. Stools may be bulky and difficult to flush, have a pale and oily appearance, and can be especially foul-smelling. An oily anal leakage or some level of fecal incon ...
) are prominent.
Cancer
Cholangiocarcinoma
Cholangiocarcinoma, also known as bile duct cancer, is a type of cancer that forms in the bile ducts. Symptoms of cholangiocarcinoma may include abdominal pain, yellowish skin, weight loss, generalized itching, and fever. Light colored stoo ...
, a major complication of PSC, is associated with a very poor prognosis. Approximately 80% of patients diagnosed with PSC-associated cholangiocarcinoma die within 1 year.
The development of any of the cancers associated with PSC predicts a poor prognosis. Complications from PSC-associated cancers account for 40% of deaths from PSC. Primary sclerosing cholangitis is one of the major known risk factors for cholangiocarcinoma, a cancer of the biliary tree, for which the lifetime risk among patients with PSC is 10-15%. This represents a 400-fold greater risk of developing cholangiocarcinoma compared to the general population. Surveillance for cholangiocarcinoma in patients with PSC is encouraged, with some experts recommending annual surveillance with a specialized imaging study and serum markers, although consensus regarding the modality and interval has yet to be established. Similarly, a screening colonoscopy
Colonoscopy () or coloscopy () is a medical procedure involving the Endoscopy, endoscopic examination of the large bowel (colon) and the distal portion of the small bowel. This examination is performed using either a Charge-coupled device, CCD ...
is recommended in people who receive a new diagnosis of primary sclerosing cholangitis since their risk of colorectal cancer is 10 times higher than that of the general population.
Related diseases
PSC is strongly associated with IBD, in particular ulcerative colitis
Ulcerative colitis (UC) is one of the two types of inflammatory bowel disease (IBD), with the other type being Crohn's disease. It is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary sympto ...
(UC) and to a lesser extent Crohn's disease
Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea, fever, abdominal distension, and weight loss. Complications outside of the ...
. As many as 5% of patients with IBD are co-diagnosed with PSC, and approximately 70% of people with PSC have IBD.[ Of note, the presence of colitis appears to be associated with a greater risk of liver disease progression and bile duct cancer (cholangiocarcinoma) development, although this relationship remains poorly understood. Close monitoring of PSC patients is vital.
Various forms of gallbladder disease such as ]gallstone
A gallstone is a stone formed within the gallbladder from precipitated bile components. The term cholelithiasis may refer to the presence of gallstones or to any disease caused by gallstones, and choledocholithiasis refers to the presence of ...
s and gallbladder polyps are also common in those with PSC. Approximately 25% of people with PSC have gallstones. Ultrasound surveillance of the gallbladder every year is recommended for people with PSC. Any person with PSC who is found to have a mass in the gallbladder should undergo surgical removal of the gallbladder due to the high risk of cholangiocarcinoma. Osteoporosis
Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk.
It is the most common reason f ...
(hepatic osteodystrophy) and hypothyroidism
Hypothyroidism is an endocrine disease in which the thyroid gland does not produce enough thyroid hormones. It can cause a number of symptoms, such as cold intolerance, poor ability to tolerate cold, fatigue, extreme fatigue, muscle aches, co ...
are also associated with PSC.
A 2–3:1 male-to-female predilection occurs in primary sclerosing cholangitis.[ PSC can affect men and women at any age, although it is commonly diagnosed in the fourth decade of life, most often in the presence of IBD.] PSC progresses slowly and is often asymptomatic, so it can be present for years before it is diagnosed and before it causes clinically significant consequences. Relatively few data are available on the prevalence
In epidemiology, prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seatbelt use) at a specific time. It is derived by comparing the number o ...
and incidence of PSC, 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, the risk is likely higher in populations where UC is more common. In the United States, an estimated 29,000 individuals have PSC.
Research
Although no curative treatment is known, several clinical trials are underway that aim to slow progression of this liver disease. Obeticholic acid is being investigated as a possible treatment for PSC due to its antifibrotic effects. Simtuzumab is a monoclonal antibody
A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell.
Monoclonal antibodie ...
against the profibrotic enzyme LOXL2 that is being developed as a possible therapy for PSC.
Notable cases
* Chris Klug – professional snowboarder with PSC who had liver transplant
* Chris LeDoux
Christopher Lee LeDoux (October 2, 1948 – March 9, 2005) was an American country music singer-songwriter, bronze sculptor, and hall of fame rodeo champion. During his career, LeDoux recorded 36 albums (many self-released), which have sold mor ...
– professional rodeo rider and country musician with PSC who died of cholangiocarcinoma
* Elena Baltacha
Elena Sergeevna Baltacha (; 14 August 1983 – 4 May 2014) was a Ukrainian-born British professional tennis player. Being a four-time winner of the AEGON Awards, she was also a long-term British No. 1, a position she held intermittently ...
– British professional tennis player, diagnosed with PSC at age 19 and died five months after being diagnosed with PSC-associated liver cancer (specifically cholangiocarcinoma) at the age of 30
* Walter Payton
Walter Jerry Payton (July 25, 1953Although most sources at the time of his death gave Payton's birth year as 1954, reliable sources subsequently state he was born in 1953. – November 1, 1999) was an American professional American football, ...
– professional American Football player and humanitarian, died of complications of PSC
* Kieron Dyer – professional footballer
* James Redford – director and son of Robert Redford
Charles Robert Redford Jr. (born August 18, 1936) is an American actor and filmmaker. He has received numerous accolades such as an Academy Award, a BAFTA Award, and two Golden Globe Awards, as well as the Cecil B. DeMille Award in 1994, the ...
who underwent two liver transplants due to PSC
* Lars-Göran Petrov – Swedish death metal vocalist best known for his work with Entombed
References
External links
Patient support organizations:
www.pscpartners.org
��based in the US
www.pscpartners.ca
��based in Canada
www.pscsupport.org.au
��based in Australia
www.pscsupport.org.uk
��based in the UK
{{Gastroenterology
Articles containing video clips
Autoimmune diseases
Biliary tract disorders
Hepatology
Inflammations