Primary Sclerosing Cholangitis (PSC)

Although the cause is unknown, primary sclerosing cholangitis (PSC) is associated with inflammatory bowel disease Overview of Inflammatory Bowel Disease Inflammatory bowel disease (IBD), which includes Crohn disease and ulcerative colitis, is a relapsing and remitting condition characterized by chronic inflammation at various sites in the gastrointestinal... read more , which is present in 80% of patients. About 5% of patients with ulcerative colitis Ulcerative Colitis Ulcerative colitis is a chronic inflammatory and ulcerative disease arising in the colonic mucosa, characterized most often by bloody diarrhea. Extraintestinal symptoms, particularly arthritis... read more and about 1% with Crohn disease Crohn Disease Crohn disease is a chronic transmural inflammatory bowel disease that usually affects the distal ileum and colon but may occur in any part of the gastrointestinal tract. Symptoms include diarrhea... read more develop primary sclerosing cholangitis (PSC). This association and the presence of several autoantibodies (eg, anti-nuclear antibodies [ANA] and perinuclear antineutrophilic antibodies [pANCA]) suggest immune-mediated mechanisms. T cells appear to be involved in the destruction of the bile ducts, implying disordered cellular immunity. A genetic predisposition is suggested by a tendency for the disorder to develop in multiple family members and a higher frequency in people with HLAB8 and HLADR3, which are often correlated with autoimmune disorders. An unknown trigger (eg, bacterial infection, ischemic duct injury) probably causes PSC to develop in genetically predisposed people.

Onset is usually insidious, with progressive fatigue and then pruritus. Jaundice Jaundice Jaundice is a yellowish discoloration of the skin and mucous membranes caused by hyperbilirubinemia. Jaundice becomes visible when the bilirubin level is about 2 to 3 mg/dL (34 to 51 micromol/L)... read more tends to develop later. About 10 to 15% of patients present with repeated episodes of right upper quadrant pain and fever, possibly due to ascending bacterial cholangitis. Steatorrhea and deficiencies of fat-soluble vitamins can develop. Persistent jaundice harbingers advanced disease. Symptomatic gallstones Cholelithiasis Cholelithiasis is the presence of one or more calculi (gallstones) in the gallbladder. In developed countries, about 10% of adults and 20% of people > 65 years have gallstones. Gallstones... read more and choledocholithiasis Choledocholithiasis and Cholangitis Choledocholithiasis is the presence of stones in bile ducts; the stones can form in the gallbladder or in the ducts themselves. These stones cause biliary colic, biliary obstruction, gallstone... read more tend to develop in about 75% of patients.

Some patients, asymptomatic until late in the course, first present with hepatosplenomegaly or cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic fibrosis that has resulted in widespread distortion of normal hepatic architecture. Cirrhosis is characterized by regenerative nodules surrounded by dense... read more . Primary sclerosing cholangitis (PSC) tends to slowly and inexorably progress. The terminal phase involves decompensated cirrhosis, portal hypertension Portal Hypertension Portal hypertension is elevated pressure in the portal vein. It is caused most often by cirrhosis (in North America), schistosomiasis (in endemic areas), or hepatic vascular abnormalities. Consequences... read more , ascites Ascites Ascites is free fluid in the peritoneal cavity. The most common cause is portal hypertension. Symptoms usually result from abdominal distention. Diagnosis is based on physical examination and... read more , and liver failure Acute Liver Failure Acute liver failure is caused most often by drugs and hepatitis viruses. Cardinal manifestations are jaundice, coagulopathy, and encephalopathy. Diagnosis is clinical. Treatment is mainly supportive... read more . The time from diagnosis to liver failure is about 12 years.

Despite the association between PSC and inflammatory bowel disease Overview of Inflammatory Bowel Disease Inflammatory bowel disease (IBD), which includes Crohn disease and ulcerative colitis, is a relapsing and remitting condition characterized by chronic inflammation at various sites in the gastrointestinal... read more , the two diseases tend to run separate courses. Ulcerative colitis Ulcerative Colitis Ulcerative colitis is a chronic inflammatory and ulcerative disease arising in the colonic mucosa, characterized most often by bloody diarrhea. Extraintestinal symptoms, particularly arthritis... read more may appear years before PSC and tends to have a milder course when associated with PSC. Similarly, total colectomy does not change the course of PSC.

The presence of both PSC and inflammatory bowel disease increases the risk of colorectal carcinoma, regardless of whether a liver transplantation Liver Transplantation Liver transplantation is the 2nd most common type of solid organ transplantation. (See also Overview of Transplantation.) Indications for liver transplantation include Cirrhosis (70% of transplantations... read more has been done for PSC. Cholangiocarcinoma develops in 10 to 15% of patients.

Primary sclerosing cholangitis (PSC) is suspected in patients with unexplained abnormalities in liver tests Laboratory Tests of the Liver and Gallbladder Laboratory tests are generally effective for the following: Detecting hepatic dysfunction Assessing the severity of liver injury Monitoring the course of liver diseases and the response to treatment... read more , particularly in those with inflammatory bowel disease Overview of Inflammatory Bowel Disease Inflammatory bowel disease (IBD), which includes Crohn disease and ulcerative colitis, is a relapsing and remitting condition characterized by chronic inflammation at various sites in the gastrointestinal... read more . A cholestatic pattern is typical: elevated alkaline phosphatase and gamma-glutamyltransferase (GGT) rather than aminotransferases. Gamma globulin and IgM levels tend to be increased. Anti-nuclear antibodies and pANCA are usually positive. Antimitochondrial antibody, positive in primary biliary cholangitis Primary Biliary Cholangitis (PBC) Primary biliary cholangitis (PBC; formerly known as primary biliary cirrhosis) is an autoimmune liver disorder characterized by the progressive destruction of intrahepatic bile ducts, leading... read more , is characteristically negative.

Imaging of the hepatobiliary system begins with ultrasonography to exclude extrahepatic biliary obstruction. Although ultrasonography or CT can show ductal dilation, diagnosis requires cholangiography to show multiple strictures and dilations in the intrahepatic and extrahepatic bile ducts. Cholangiography should begin with magnetic resonance cholangiopancreatography Magnetic resonance imaging (MRI) (MRCP). Endoscopic retrograde cholangiopancreatography Endoscopic retrograde cholangiopancreatography (ERCP) Imaging is essential for accurately diagnosing biliary tract disorders and is important for detecting focal liver lesions (eg, abscess, tumor). It is limited in detecting and diagnosing diffuse... read more (ERCP) is usually a 2nd choice because it is invasive. Liver biopsy Liver Biopsy Liver biopsy provides histologic information about liver structure and evidence of liver injury (type and degree, any fibrosis); this information can be essential not only to diagnosis but also... read more is usually not required for diagnosis; when done, it shows bile duct proliferation, periductal fibrosis, inflammation, and loss of bile ducts. With disease progression, periductal fibrosis extends from the portal regions and eventually leads to secondary biliary cirrhosis.

Adults with PSC should undergo abdominal imaging Imaging Tests of the Liver and Gallbladder Imaging is essential for accurately diagnosing biliary tract disorders and is important for detecting focal liver lesions (eg, abscess, tumor). It is limited in detecting and diagnosing diffuse... read more (ultrasound, abdominal computed tomography, or magnetic resonance imaging/magnetic resonance cholangiopancreatography) every 6 to 12 months to screen for gallbladder cancer and cholangiocarcinoma Tumors of the Gallbladder and Bile Ducts Gallbladder and bile duct tumors can cause extrahepatic biliary obstruction. Symptoms may be absent but often are constitutional or reflect biliary obstruction. Diagnosis is based on ultrasonography... read more . Serum levels of carbohydrate antigen (CA) 19-9 should be monitored regularly (1 Diagnosis reference Primary sclerosing cholangitis (PSC) is patchy inflammation, fibrosis, and strictures of the bile ducts that has no known cause. However, 80% of patients also have inflammatory bowel disease... read more ).

Colonoscopy Screening tests Colorectal cancer is extremely common. Symptoms include blood in the stool and change in bowel habits. Screening using one of several methods is recommended for appropriate populations. Diagnosis... read more with biopsies Liver Biopsy Liver biopsy provides histologic information about liver structure and evidence of liver injury (type and degree, any fibrosis); this information can be essential not only to diagnosis but also... read more should be done in patients without pre-existing inflammatory bowel disease Overview of Inflammatory Bowel Disease Inflammatory bowel disease (IBD), which includes Crohn disease and ulcerative colitis, is a relapsing and remitting condition characterized by chronic inflammation at various sites in the gastrointestinal... read more (IBD) at the time of diagnosis of PSC and should be carried out annually in PSC patients with IBD from the time of diagnosis of PSC due to the increased risk of colorectal adenocarcinoma.

Asymptomatic patients usually require only monitoring (eg, physical examination and liver tests twice/year) and, if adults, periodic imaging and measurement of CA 19-9 for gallbladder cancer and cholangiocarcinoma screening. Ursodeoxycholic acid (up to 20 mg/kg/day) reduces itching and improves biochemical markers but not survival. Chronic cholestasis and cirrhosis require supportive treatment. Episodes of bacterial cholangitis warrant antibiotics and therapeutic ERCP Endoscopic retrograde cholangiopancreatography (ERCP) Imaging is essential for accurately diagnosing biliary tract disorders and is important for detecting focal liver lesions (eg, abscess, tumor). It is limited in detecting and diagnosing diffuse... read more as needed (1 Treatment reference Primary sclerosing cholangitis (PSC) is patchy inflammation, fibrosis, and strictures of the bile ducts that has no known cause. However, 80% of patients also have inflammatory bowel disease... read more ). If a single stricture appears to be the major cause of obstruction (a dominant stricture, found in about 20% of patients), ERCP dilation (with brush cytology and fluorescence in situ hybridization [FISH] to screen for cholangiocarcinoma) and stenting can relieve symptoms.

Liver transplantation Liver Transplantation Liver transplantation is the 2nd most common type of solid organ transplantation. (See also Overview of Transplantation.) Indications for liver transplantation include Cirrhosis (70% of transplantations... read more is the only treatment that improves life expectancy in patients with primary sclerosing cholangitis and that offers a cure. Recurrent bacterial cholangitis or complications of end-stage liver disease (eg, intractable ascites Ascites Ascites is free fluid in the peritoneal cavity. The most common cause is portal hypertension. Symptoms usually result from abdominal distention. Diagnosis is based on physical examination and... read more , portosystemic encephalopathy Portosystemic Encephalopathy Portosystemic encephalopathy is a neuropsychiatric syndrome that can develop in patients with liver disease. It most often results from high gut protein or acute metabolic stress (eg, gastrointestinal... read more , bleeding esophageal varices Varices Varices are dilated veins in the distal esophagus or proximal stomach caused by elevated pressure in the portal venous system, typically from cirrhosis. They may bleed massively but cause no... read more ) are indications for liver transplantation.