Primary Sclerosing Cholangitis (PSC)

What is primary sclerosing cholangitis?

Primary sclerosing cholangitis (PSC) is a chronic disease of the bile ducts that can cause long-standing inflammation, narrowing and scarring (fibrosis) in the bile ducts within and/or outside the liver.

Narrowings and dilatations may form in different parts of the bile ducts over time. The flow of bile may be disturbed, and as the disease advances the liver may also be damaged.

The course of PSC varies considerably from person to person. Some people have no significant trouble for many years, while in others the disease may progress over time.

Why does PSC occur?

The exact cause of PSC is not fully known.

The immune system, genetic susceptibility, the bowel microbiota and environmental factors are thought to play a part together.

But describing PSC simply as “an autoimmune disease” is not entirely accurate either.

The disease is not contagious.

In whom does PSC occur?

PSC is an uncommon disease.

Although it can appear at any age, it is diagnosed more often in young and middle-aged adults, and is seen more often in men than in women.

One of the most striking features of PSC is its strong association with inflammatory bowel disease (IBD).

What is the relationship between PSC and ulcerative colitis?

A substantial proportion of patients with PSC have inflammatory bowel disease — ulcerative colitis, or less often Crohn’s disease.

Sometimes the bowel disease is found before the PSC, sometimes after.

Interestingly, inflammation may be found in the colon even in a patient with PSC whose bowel complaints are mild or who has none at all.

For this reason it is important to assess whether inflammatory bowel disease is present in patients newly diagnosed with PSC.

What are the symptoms of PSC?

Some patients may have no symptoms at all, and the disease may come to light only while raised liver enzymes on routine blood tests are being investigated.

Where symptoms do develop, there may be:

• Weakness,
• Itching,
• Discomfort or pain in the right upper abdomen,
• Jaundice,
• Dark urine,
• Pale stools.

In advanced disease, other findings of chronic liver disease may appear.

How is PSC recognised on blood tests?

In PSC, because of the disturbance in the bile ducts, a rise in alkaline phosphatase (ALP) and GGT in particular may be seen.

AST and ALT may also be raised.

Where the flow of bile is markedly disturbed, bilirubin may rise.

But blood tests do not on their own establish a diagnosis of PSC.

Nor do the levels of the blood values always show exactly how extensive the disease is within the bile ducts.

How is PSC diagnosed?

The diagnosis is made by assessing together:

the clinical findings + blood tests + imaging of the bile ducts.

Today one of the most important methods for assessing the bile ducts is MRCP.

Why does MRCP matter?

Magnetic resonance cholangiopancreatography (MRCP) can image the bile ducts in detail without any procedure.

In PSC, an irregular appearance may emerge in different parts of the bile ducts:

narrowing → dilatation → narrowing again.

One of the advantages of MRCP is that it needs no endoscopic procedure.

For this reason MRCP is generally preferred to ERCP in diagnosing PSC.

Is an ERCP done in every patient with PSC?

No.

Because ERCP is an interventional procedure, it is not done routinely merely to make a diagnosis of PSC.

But it can be very valuable in certain situations.

An ERCP may be needed, for instance:

• Where a significant biliary stricture is suspected,
• Where jaundice becomes marked,
• Where recurrent cholangitis develops,
• Where a stricture suspicious for bile duct cancer appears.

During ERCP a stricture can be treated where needed, and samples such as brush cytology or a biopsy can be taken.

Is there a place for EUS?

Yes.

Endoscopic ultrasound (EUS) can be useful particularly where there is a stricture of unexplained cause, a mass around the bile duct, or suspicious lymph nodes.

EUS can assess the pancreas and the region around the bile ducts at high resolution, and allows a tissue sample to be taken in selected situations.

Is a liver biopsy needed?

A liver biopsy is not needed in every patient with PSC.

In patients with typical MRCP findings a biopsy is mostly not required.

But a biopsy may be needed in situations such as small-duct PSC, where PSC is suspected although imaging of the bile ducts is normal, or where another liver disease is suspected alongside it.

What is small-duct PSC?

In some patients there are clinical and laboratory findings resembling PSC, but the typical changes are not seen in the large bile ducts on MRCP.

This is called small-duct PSC.

A liver biopsy may be important in making the diagnosis.

In some patients, classical PSC affecting the large bile ducts may develop over time.

Why does a biliary stricture matter in PSC?

PSC can already cause a large number of strictures in the bile ducts.

But in some patients a more significant stricture may appear in a particular area, seriously obstructing the flow of bile.

In that situation:

the jaundice may increase → the itching may increase → cholangitis may develop.

In a new or progressing stricture, cholangiocarcinoma may also need to be excluded.

What is cholangitis?

Bacterial infection can develop in narrowed bile ducts. This is called acute cholangitis.

The combination of:

fever + jaundice + abdominal pain

matters in particular.

The development of shivering, low blood pressure or a change in consciousness may suggest a more serious infection.

Acute cholangitis may require antibiotic treatment and, in some patients, urgent opening of the obstructed bile duct.

Is there a treatment for PSC?

Treatment of PSC is planned according to the patient’s situation.

At present there is no single drug treatment that has been shown definitely to stop the progression of the disease in all patients with PSC.

The main aims of treatment can be summarised as:

• Reducing the patient’s symptoms,
• Treating obstructions of the bile ducts,
• Treating and preventing cholangitis,
• Assessing nutrition and bone health,
• Detecting complications early,
• Managing advanced liver disease.

Is ursodeoxycholic acid used?

Ursodeoxycholic acid (UDCA) is a drug that has been investigated in PSC for many years.

It can improve the liver tests in some patients. But it has not been shown definitely to prevent the long-term course of the disease or its complications.

Its use and dose should therefore be assessed individually by a gastroenterologist or hepatologist.

It is known in particular that high-dose UDCA is not beneficial and may be harmful.

How are biliary strictures treated?

Where a patient has a clinically significant biliary stricture, balloon dilatation may be carried out during ERCP in suitable patients.

In some selected situations a short-term stent may be needed.

Not every stricture in PSC needs a stent.

Treatment is decided according to the site of the stricture, the patient’s symptoms and the risk of infection.

Can PSC cause cirrhosis?

Yes.

Long-standing damage in the bile ducts can progress over time to fibrosis in the liver and, in some patients, to cirrhosis.

In advanced disease, complications such as:

• Portal hypertension,
• Fluid collecting in the abdomen (ascites),
• Oesophageal varices,
• Enlargement of the spleen,
• Deterioration of liver function

may develop.

But the rate at which the disease progresses differs greatly from person to person.

Does PSC increase the risk of bile duct cancer?

Yes.

PSC is one of the important risk factors for cholangiocarcinoma (bile duct cancer).

Detailed assessment is therefore needed particularly where there is:

• New or rapidly increasing jaundice,
• A marked new biliary stricture,
• Unexplained weight loss,
• An unexpected deterioration in the liver tests.

But it needs stressing again:

not every biliary stricture seen in PSC is cancer.

Does PSC increase the risk of bowel cancer?

In people who have PSC together with inflammatory bowel disease in particular, the risk of colorectal cancer is higher than in people with inflammatory bowel disease alone.

For this reason colonoscopic follow-up matters especially where PSC and IBD occur together, and it may be done more often than in the general population.

The follow-up programme is decided according to the patient’s situation.

Is the gallbladder followed up too?

Polyps or mass-like changes may be seen in the gallbladder in patients with PSC.

The gallbladder is therefore also assessed during imaging.

The management of gallbladder polyps found in these patients may require a different assessment from polyps in the general population.

Why does bone health matter in PSC?

A fall in bone mineral density can develop in chronic cholestatic liver diseases.

For this reason the vitamin D level, calcium metabolism and bone density may need to be assessed in suitable patients.

In long-standing, severe cholestasis the absorption of the fat-soluble vitamins A, D, E and K may also be affected.

Is a liver transplant needed?

In advanced PSC, liver transplantation is an important treatment option.

Transplantation may be considered in selected patients with:

• Advanced liver failure,
• Complications of cirrhosis,
• Recurrent severe cholangitis despite treatment,
• Certain serious symptoms that cannot be controlled.

In some very particular and selected patients with perihilar cholangiocarcinoma, different transplantation protocols can also be used at specialist centres.

How are patients with PSC followed up?

PSC is a chronic disease requiring long-term follow-up.

Depending on the patient’s situation, follow-up may involve:

• Liver tests,
• Clinical assessment,
• MR/MRCP and other imaging,
• Assessment of the gallbladder,
• Assessment for cholangiocarcinoma,
• Regular colonoscopy where there is accompanying IBD,
• Assessment of bone health.

The frequency of follow-up is not the same in all patients.

When is emergency assessment needed?

In a patient with PSC, if there develops:

• Fever and shivering,
• New or rapidly increasing jaundice,
• Severe right upper abdominal pain,
• Low blood pressure,
• A change in consciousness,
• A marked deterioration in general condition,

acute cholangitis or serious obstruction of the bile duct may be present.

Medical assessment is then needed without delay.

Remember

Primary sclerosing cholangitis is a disease that can cause chronic inflammation, strictures and fibrosis in the bile ducts.

PSC has a strong association with inflammatory bowel disease, and with ulcerative colitis in particular.

MRCP is one of the main imaging methods in making the diagnosis, because it can show the bile ducts without any procedure. ERCP, rather than being a routine diagnostic test, is used to treat significant strictures and to take samples where needed.

PSC can increase the long-term risk of cirrhosis, recurrent cholangitis and cholangiocarcinoma. In people who have PSC together with inflammatory bowel disease, regular follow-up for bowel cancer also matters.

For this reason the disease needs to be followed not only in terms of the liver enzymes but in terms of the bile ducts, the bowels and the long-term complications together.