Primary sclerosing cholangitis (PSC): Chronically inflamed bile ducts

What is primary sclerosing cholangitis (PSC)?

Primary sclerosing cholangitis is a rare chronic disease. It causes your bile ducts to become permanently inflamed. At the same time, the connective tissue (fibrosis) surrounding the bile ducts increases abnormally, causing them to narrow and harden (sclerosis). Bile can no longer flow unhindered from the liver into the intestine, but accumulates in front of the constrictions. This accumulation of bile is also called cholestasis.

As a consequence, too little bile reaches your small intestine, so that it cannot support fat digestion there. In addition, components of the accumulated bile have a poisonous (toxic) effect on the liver cells, which can damage the organ. Primary sclerosing cholangitis usually develops slowly and leads to liver cirrhosis in the final stage.

PSC is a relatively rare disease. The frequency of the disease varies, but it is estimated that between four and 16 in 100,000 people are affected. Men fall ill two to three times as often as women. Primary sclerosing cholangitis often remains undetected for a long time. The diagnosis is usually made between the ages of 30 and 50.

Primary sclerosing cholangitis (PSC): causes and risk factors

It is still unclear why primary sclerosing cholangitis develops. However, there are probably several causes. It is certain that genetic factors play a role. They may lead to the disease in combination with other influences. Experts are still discussing what these influences are. Some believe that PSC is caused by a misdirected immune reaction to the mucous membrane of the bile ducts. The microorganisms in the digestive tract may also play a role in this.

Risk factors for inflammatory bowel disease

It is striking that up to 70 out of 100 people with PSC also suffer from chronic inflammatory bowel disease, primarily ulcerative colitis, and less frequently Crohn’s disease. Conversely, around five percent of all ulcerative colitis sufferers develop PSC. In addition, the rare disease often occurs together with various autoimmune diseases such as autoimmune hepatitis or Sjögren’s syndrome.

Symptoms: PSC often remains undetected for a long time

If you suffer from PSC, you will usually not show any symptoms at the beginning of the disease. This is why it is either discovered as an incidental finding or only at an advanced stage.

Typical signs of advanced primary sclerosing cholangitis occur when the bile ducts are damaged to such an extent that the liver no longer works properly. Symptoms such as:

• Tiredness, fatigue
• Weight loss
• Itching
• Tenderness and/or pain in the right upper abdomen
• Jaundice: Yellowing of the skin and mucous membranes (so-called jaundice)

Primary sclerosing cholangitis: diagnosis with us

If the inflammation of the bile ducts is already advanced, symptoms such as jaundice of the skin and mucous membranes or itching all over the body can be the first signs of primary sclerosing cholangitis.

If you seek medical advice with symptoms that indicate the disease, you will first be asked a medical history, i.e. questions about your medical history including any previous illnesses. Among other things, it is important to know whether you may be suffering from a chronic inflammatory bowel disease. The background to this is that 70 percent of people with PSC have a corresponding bowel disease, in particular ulcerative colitis, and possibly also Crohn’s disease.

Blood test

If the bile ducts are inflamed and the bile can no longer drain away properly, bile stasis (cholestasis) occurs. In most cases, certain blood values are then elevated, the so-called cholestasis parameters (such as gamma-GT, alkaline phosphatase and bilirubin).

However, there is no specific liver value that clearly indicates primary sclerosing cholangitis. Although elevated liver values can indicate PSC, they are not sufficient for a definitive diagnosis – as many other diseases also cause elevated liver values.

Ultrasound

We can use ultrasound to inspect the liver and bile ducts. This can make it possible to differentiate a possible PSC from other conditions. If the suspicion is confirmed, the bile ducts must be examined more closely for a precise diagnosis. There are two main methods available to us: ERCP and MRCP.

MRCP (magnetic resonance cholangiopancreatography)

MRCP (magnetic resonance cholangiopancreatography) is an MRI scan of the liver and bile ducts. If primary sclerosing cholangitis is present, pearl-like irregularities of the imaged bile ducts can often be seen. Changes in the bile ducts reminiscent of a string of pearls are typical of PSC: the sections narrowed by the inflammation alternate with sac-shaped dilatations. They occur when bile builds up in front of the constrictions.

If the MRCP reveals unclear findings or if constrictions are detected that should be treated, we sometimes carry out an ERCP afterwards.

ERCP (endoscopic retrograde cholangiopancreatography)

ERCP makes it possible to visualize the bile ducts and gallbladder in great detail. ERCP not only helps with diagnosis. It can also be used for therapy by stretching existing constrictions in a bile duct during the procedure.

You will be given a sleeping pill or sedative before the ERC, so you will not be aware of the scan. We insert a flexible tube, the endoscope, through your mouth and push it through the stomach into the duodenum to the so-called Vater’s papilla, where the common bile duct and pancreatic duct meet. The endoscope is equipped with a light source and an optical system. A contrast medium is now injected into the bile duct system. We then take an X-ray of the area. This enables us to detect the scarring and narrowing of the bile ducts typical of PSC and also to detect tumors.

A liver puncture can also be helpful. We use a puncture syringe to remove some liver tissue and have this examined in the laboratory.

Primary sclerosing cholangitis: prevention, early detection, prognosis

It is not possible to prevent primary sclerosing cholangitis. However, the earlier the disease is detected, the better the late effects of the disease can be recognized and treated.

Early detection of the disease is also difficult, as it is not noticeable at first. However, a chronic inflammatory bowel disease, especially ulcerative colitis, less frequently Crohn’s disease, increases the risk of developing PSC. If you are affected by this, have your liver values checked regularly and, if suspected, have your bile ducts examined. Unexplained itching or jaundice of the skin and mucous membranes indicate liver disease or advanced primary sclerosing cholangitis. Always seek medical advice if you have symptoms so that the cause can be identified.

Course and prognosis

Primary sclerosing cholangitis usually develops slowly and varies greatly depending on the person affected. The chronic inflammation causes connective tissue around the bile ducts to proliferate pathologically. In the final stage, complete scarring of the liver can occur, leading to liver cirrhosis. As a result, the organ can no longer fulfill its functions

Impending consequential damage

Various secondary damage and complications can occur – but they do not affect everyone with PSC. The possible consequences include

• a deficiency of fat-soluble vitamins (A, D, E, K)
• rheumatic complaints
• Osteoporosis (bone loss)
• Acute biliary tract infections (acute cholangitis)
• Stones in the gallbladder and bile duct
• Cirrhosis of the liver
• Tumors of the bile ducts, colon, pancreas, liver

If you suffer from PSC, this results in an increased risk of certain types of cancer. This is why you should have regular screening examinations:

• An annual colonoscopy in the case of coexisting colitis
• An ultrasound examination of the liver every six months, alternating with MR imaging of the liver and bile ducts. In addition, a six-monthly determination of the tumor marker CA 19-9.

Prognosis of the PSC

According to studies, the average survival time after a diagnosis of PSC is around ten to 20 years if no liver transplant is performed. However, many patients can live significantly longer with a liver transplant.

As the course of primary sclerosing cholangitis can vary greatly, the prognosis also varies from case to case. In addition, it is not yet possible to assess with certainty what effects the long-term administration of ursodeoxycholic acid has on the prognosis. Regular examinations for the early detection of malignant tumors in the intestines and bile ducts can significantly improve the prospects.

Researchers are currently testing whether the active substance nor-ursodeoxycholic acid (norUDCA), a chemical modification of ursodeoxycholic acid, leads to a better prognosis. Without a liver transplant, life expectancy is lower, although these are average values that can vary considerably in individual cases.

Small duct PSC, in which only the small bile ducts are initially affected, usually has a more favorable prognosis. Women appear to be more frequently affected by this disease. However, it can also develop into classic PSC. The frequency of this variant of the disease is still being investigated.

Primary sclerosing cholangitis: treatment prevents late effects

To date, there is no treatment concept that could cure primary sclerosing cholangitis. The aim of treatment is to positively influence the course of the disease, improve quality of life and prevent long-term consequences.

The focus is on the active ingredient ursodeoxycholic acid and endoscopic dilatation (widening) of the narrowed bile ducts. If PSC has already severely damaged your liver or a malignant tumor has developed in the bile ducts, a liver transplant is usually necessary.