Primary sclerosing cholangitis
This article was last reviewed and updated on October 3, 2018
by Stephanie Reid, MD FRCPC
Primary sclerosing cholangitis is a liver disease caused by cells from the immune system attacking and damaging the cells that line small channels in the liver called ducts.
This damage prevents the liver from functioning normally.
Long standing primary sclerosing cholangitis can lead to a condition called cirrhosis.
The liver is an organ found in the right upper part of your abdominal cavity. It is responsible for removing toxins, processing medications, and producing substances such as bile that are essential for breaking down and using food.
The liver can be affected by diseases other than tumours. These are broadly referred to as ‘medical liver disease’. In these diseases, there is damage to specific cell types or areas of the liver. The liver contains multiple types of cells which make up its structure and contribute to function. The main type of cell in the liver is called a hepatocyte. The liver also has biliary cells which line the inside of long channels called bile ducts, and endothelial cells which line the inside of blood vessels. There are also a variety of background cells and materials that support and hold all these other parts of the liver together. In medical liver disease, any of these structures may be affected or damaged.
Some medical liver diseases belong to a category called “autoimmune disease”. In these diseases, your liver is damaged by cells from your immune system (the cells that normally help you fight off viruses and other types of infections). These diseases are classified by which cells or parts of the liver are damaged by the immune cells. The causes of autoimmune liver disease are not fully understood although some are associated with other medical conditions.
Primary sclerosing cholangitis (PSC) is a type of medical liver disease that damages the bile ducts inside and draining the liver. It is frequently associated with a condition called inflammatory bowel disease (particularly ulcerative colitis). PSC occurs most commonly in young and middle-aged men. Most patients have no symptoms when diagnosed but blood work may reveal elevated levels in a blood test called alkaline phosphatase in over 90% of patients. Other nonspecific symptoms that can occur include fatigue, itchy skin, abdominal pain, yellow skin, and weight loss.
There are several complications of primary sclerosing cholangitis. A major one is liver cirrhosis, which usually occurs 10-15 years after diagnosis. When this occurs, patients may require a liver transplant. PSC also increases the risk of cholangiocarcinoma (cancer of the bile ducts).
If primary sclerosing cholangitis is suspected, your doctor will order a radiologic test called a magnetic resonance cholangiopancreatography (MRCP) or cholangiography. Classic findings of PSC in these tests include bile ducts that have a beaded appearance caused by multiple areas of narrowing.
Pathologic features of primary sclerosing cholangitis
A liver biopsy is performed in primary sclerosing cholangitis mainly to determine the amount of ducts that have disappeared due to damage, and also the amount of scarring (fibrosis) within the liver. When examining your tissue sample under the microscope, your pathologist will look for several important microscopic features:
Bile duct damage: The liver produces a substance called bile which is used to remove toxins from the body and digest food. The bile produced in the liver drains through channels called bile ducts into the small bowel. Each portal tract contains one bile duct. Your pathologist will look for bile duct damage or active inflammation around the bile ducts.
Bile duct loss: If damage or inflammation continues for a prolonged period of time, bile ducts may be scarred and lost. This will result in portal tracts that only have blood vessels. Your pathologist may record the amount of bile duct loss in multiple ways including stating the actual number lost, the percentage lost, or the degree of loss (mild, moderate, or severe). Some pathologists use the word ductopenia to describe a decreased number of bile ducts.
Concentric fibrosis: Concentric fibrous describes a type of reaction where fibrous cells surround the bile ducts and cause an injury that looks like an “onion skin” when viewed through a microscope. While this type of injury is not seen in all biopsies, when found it is highly supportive of the diagnosis of PSC.
Cholestasis: Cholestasis is a word pathologists use to describe bile trapped in the liver. Trapped bile is important because it can cause liver injury. If cholestasis is seen, your pathologist will describe its location within the liver and the amount of trapped bile will be described as mild, moderate, or severe. Because primary sclerosing cholangitis damages the bile ducts, there is often cholestasis present in the liver biopsy.
Fibrosis: Fibrosis is a type of scar tissue that forms in the liver after damage. Because PSC damages the liver, there is a risk of developing fibrosis. Most pathology reports comment on the amount of fibrosis and will give it a ‘stage’. The stage is dependent on multiple factors including extent of initial injury, the length of time injury was occurring, and which parts of the liver were damaged. Too much fibrosis disrupts the architecture of the liver and prevents it from functioning properly.
There are several different classifications systems used to stage fibrosis but all of them include the type and amount of fibrosis seen. Cirrhosis is the last stage of fibrosis and it is characterized by large fibrous bands in the liver. In diseases that affect the bile ducts (such as PSC), the fibrosis may be patchy and irregular. It prevents the liver from carrying out its normal functions and may lead to a medical condition called ‘liver failure’.
The liver is divided into ‘zones’ and at the center of each zone is a structure called a ‘portal tract’. Portal tracts are important because they contain blood vessels and channels that move other substances such as bile in and out of the liver.
When examining a liver biopsy, your pathologist must first determine if the sample contains the minimum amount of portal tracts required to make an accurate diagnosis. The adequacy of the biopsy may be reported simply as “yes” or “no”, or the number of portal tracts seen may be stated.
The condition of the liver biopsy when viewed under the microscope is usually described. If the liver biopsy is brittle and has broken apart this will be described, as it may be a clue to specific liver conditions.
Steatosis is the term used to describe the presence of fat droplets within the hepatocytes. In steatosis, the hepatocytes contain clear areas of fat droplets when viewed under a microscope.
Pathologists use a scale to describe the amount of fat in a liver with steatosis. The scale is based on the percentage of liver cells that contain fat droplets:
The scale used by most pathologists includes:
Mild - fat droplets are seen within less than 33% of the hepatocytes in the biopsy
Moderate - fat droplets are seen within 33 - 66 % of hepatocytes in the biopsy
Severe - fat droplets are seen within greater than 66 % of hepatocytes in the biopsy.
Ballooning hepatocytes are liver cells which are damaged or dying. The hepatocyte swells to several times its normal size and becomes clear in areas. Ballooning hepatocytes are required for the diagnosis of several medical liver diseases. The amount of hepatocyte ballooning present is reported as mild, moderate, or severe.
Mallory bodies form because of damage to hepatocytes. Under the microscope they look like dark pink material inside of the cells. Mallory bodies are present in specific forms of liver disease and their presence or absence helps guide pathologists to a diagnosis.
Iron can build up within the liver as a result of abnormal breakdown of iron, increased iron in the body (such as after multiple blood transfusions), or when the liver is not functioning properly (as in liver cirrhosis). This excess iron can be seen within the hepatocytes or within immune cells called macrophages. If iron is present in your tissue, your pathologist will report its location and severity.