What Is Primary Sclerosing Cholangitis?

Overview

Primary sclerosing cholangitis (PSC) is a chronic condition affecting the bile ducts, the tube-like vessels that carry bile from the liver to the small intestine. It is a rare disease, but those affected by the disease may develop liver failure and other gastrointestinal complications.

Read on to learn more about this condition and the symptoms to look out for.

Causes of primary sclerosing cholangitis

First, let’s break down the name to understand the disease.

‘Primary’ indicates that there is no trigger or other preceding event for the disease.

‘Sclerosing’ indicates the narrowing and hardening of the bile ducts that occurs as part of primary sclerosing cholangitis.

‘Cholangitis’ is an inflammation of the bile ducts.

Therefore, primary sclerosing cholangitis occurs when the bile ducts of the biliary system become inflamed and then harden and become narrow.

What is the biliary system?

The biliary system is a subsystem of the digestive system that relates to the production, storage, and transportation of bile, a substance produced by the liver to aid in fat digestion.

The biliary system consists of the liver, the bile ducts, and the gallbladder. Bile is produced in the liver and travels through bile ducts to be stored in the gallbladder. During digestion, bile travels in the bile ducts to the first part of the small intestine.

What happens in PSC?

In primary sclerosing cholangitis, sclerosis (narrowing and hardening) of the bile ducts causes the bile ducts to become blocked in multiple areas. Bile builds up behind these blockages in the bile ducts and flows back into the liver, irritating it. The back pressure of bile in the system serves to further damage the liver. This process worsens over time, causing the liver to become chronically inflamed.

If unmanaged, chronic inflammation of the liver can progress into reversible scarring (fibrosis), and then cirrhosis, which is irreversible, permanent scarring of the liver, demonstrates a degree of end-stage liver failure. 

Why do the bile ducts become sclerosed?

It is thought that the bile ducts become sclerosed as part of an immune-mediated process, but there is no consensus yet.

Risk factors

Most people with primary sclerosing cholangitis are diagnosed between the ages of 30 and 40, with twice as many men diagnosed with the condition as women.¹

There is an increased risk of developing primary sclerosing cholangitis if any of your relatives have the disease.³

There is a well-established link between PSC and inflammatory bowel disease (IBD). Studies demonstrate that between 60-70% of PSC patients also have inflammatory bowel disease.^2,3,4 However, having an inflammatory bowel disease doesn’t mean that someone will develop PSC—they just have a higher risk. Only 2.2% of IBD patients had PSC in a study conducted to demonstrate the incidence of PSC in IBD patients.⁵

Signs and symptoms of primary sclerosing cholangitis

The signs and symptoms associated with primary sclerosing cholangitis are usually progressive, which reflects the nature of the disease. Initially, symptoms begin mildly and gradually worsen over time.

Patients experience few or no symptoms during the early stages of the disease. Unfortunately, by the time patients do experience symptoms, it can indicate that the condition has progressed further or that they have developed complications as a consequence of the disease. It is important to attend any screening appointments as this can facilitate an early diagnosis of the disease.

Common symptoms in primary sclerosing cholangitis include:

•  Fatigue (persistent excessive tiredness)
• Jaundice (skin and eyes appearing yellow)
• Right upper abdominal pain
• Pruritis (itching)
• Fever
• Weight loss

Diagnosis of primary sclerosing cholangitis

Patients will undergo blood tests which seek to assess the liver’s function. These tests are called liver function tests (LFTs). 75% of PSC patients have abnormal LFTs.⁶

The best way of determining whether a person has primary sclerosing cholangitis is a type of imaging scan called a magnetic resonance cholangiopancreatography (MRCP), which is an MRI scan that allows doctors to visualise the structures of the biliary system. To make a diagnosis of primary sclerosing cholangitis, narrowing of the bile ducts inside and outside of the liver should be seen.

A liver biopsy can help to differentiate between primary sclerosing cholangitis and other similarly presenting liver diseases, such as primary biliary cholangitis (also known as primary biliary cirrhosis) or autoimmune hepatitis.

Management and treatment for primary sclerosing cholangitis

Once sclerosis has begun, no treatments can reverse or halt the process. However, some treatments can manage the symptoms associated with primary sclerosing cholangitis and promote the movement of bile.^7,8 There is also a focus on preventing complications, such as cirrhosis.

These include:

Medications 

• Ursodeoxycholic acid (UDCA)–UDCA is found to reduce certain LFTs, but has demonstrated limited or no effects on slowing disease progression
• Colestyramine May be used to manage symptoms like itching of the condition

Procedures

•  Endoscopic retrograde cholangiopancreatography (ERCP): Doctors can insert hollow tubes (stents) or small balloons (ballooning) into narrowed bile ducts to open them up and promote bile movement during this procedure
• Liver transplantation can be an option in severe or advanced cases of primary sclerosing cholangitis. A liver transplant can eliminate the condition, but there is a chance of recurrence.⁹ Liver transplants are also associated with several risks, including:
  • Liver rejection
  • Use of immunosuppressive agents for life to prevent body immunity from harming the transplanted cells
  • Consequent increased susceptibility to infections
  • Risk of developing cancers from the use of immunosuppressive agents

As always, the best treatment for the disease is dependent on individual circumstances, and a gastroenterologist (a doctor who manages the digestive system and liver) will discuss the appropriate treatments with the patient.

Complications

Primary sclerosing cholangitis has been associated with the development of:

• Cirrhosis and liver failure
• Acute bacterial cholangitis (bacterial infection of the bile ducts)
• Inflammatory bowel diseases (ulcerative colitis and/or Crohn’s disease)
• Fat-soluble vitamin deficiencies (A, D, E, K)
• Colorectal cancers
• Cholangiocarcinoma (cancer of the bile ducts)

See our article on cholangiocarcinoma here!

FAQs

How common is primary sclerosing cholangitis?

• 5 to 16 people per 100,000 are estimated to have PSC
• There are questions about how accurate these values are. Several cases of primary sclerosing cholangitis go undiagnosed since a large proportion of PSC patients experience no symptoms and therefore never receive a diagnosis

How can I prevent primary sclerosing cholangitis?

• Primary sclerosing cholangitis cannot be prevented since a specific cause has not been identified yet
• However, it is important to take note of your general health and speak to a healthcare professional if you notice any changes, especially if you have any positive risk factors (family history of PSC, diagnosis of inflammatory bowel disease, male sex, 30-40 years old)

When should I see a doctor?

 If you are experiencing persistent and progressively worsening symptoms such as fatigue, jaundice, weight loss, or itching, you should make an appointment with a healthcare professional.

Summary

In summary, primary sclerosing cholangitis is an immune-mediated progressive disease of the bile ducts associated with an increased risk of cancer. Early diagnosis is key to mitigating the risk of developing any severe complications, such as liver cirrhosis or failure.

See your healthcare provider as soon as possible if you notice yellow discolouration of the eyes or skin, especially if it is accompanied by abdominal pain, weight loss, excessive fatigue, or itching.

Attend all screening or routine health evaluation appointments, even if you feel well. Early diagnosis can be key in the management of the condition and in reducing the chances of severe complications.