Primary Sclerosing Cholangitis – Symptoms and Treatment

Definition and Causes:

Primary sclerosing cholangitis (PSC) is a chronic inflammation of the large and medium bile ducts inside and outside the liver, leading to narrowing of these ducts, disruption of bile flow, and liver damage.

PSC can be:

  • Primary – occurs for unknown reasons.
  • Secondary – developing against a background of acquired (in adults) or congenital (in children) immune impairment, often associated with an exaggerated response to infection, accumulation of histiocytic cells, or medication use. Both types (primary and secondary) result in inflammatory and tissue changes with the formation of fibrotic tissue affecting bile duct passage.

Bile duct narrowing (strictures) can result not only from inflammation but also from other causes such as surgical procedures, ischemic injury to the bile ducts (during liver transplantation), developmental anomalies, bile duct cancer, or parasitic infections.

Often, PSC is discovered during the diagnosis and treatment of the primary condition. In such cases, the focus is on treating the causes leading to bile duct narrowing.

PSC may persist for a long time without symptoms or may manifest as skin itching and fatigue. Due to this progression, patients seek medical care when they are in the advanced stage, followed by liver cirrhosis. Therefore, this article will focus more on primary sclerosing cholangitis.

Causes of Primary Sclerosing Cholangitis:
The exact cause of primary sclerosing cholangitis is unknown. Genetic and environmental factors play a significant role in the disease’s occurrence. Microorganisms in the intestines are also believed to influence disease development, as around 70% of primary sclerosing cholangitis patients have accompanying inflammatory bowel diseases.

Prevalence of Primary Sclerosing Cholangitis:
Primary sclerosing cholangitis is considered a rare disease, with an incidence rate of up to 16 cases per 100,000 people. The highest prevalence rates are recorded in Northern Europe, with the lowest rates in South America, Africa, and Asia.

  • The disease often occurs more frequently in males (65-70%) and is usually diagnosed between the ages of 30 and 40.
    The disease progresses slowly. In a study conducted in the Netherlands, it was found that patients lived, on average, for 21.3 years after diagnosis until undergoing liver transplantation or experiencing death related to primary sclerosing cholangitis.

Symptoms of Primary Sclerosing Cholangitis:

Symptoms of the disease gradually appear as it progresses, causing damage to the bile ducts and the formation of scar tissue, leading to narrowing, bile retention, and gradual liver fibrosis.

  • The disease can persist for a long time without symptoms. As the disease progresses, symptoms such as fatigue, itching, and pain in the lower right side may appear.
  • Fatigue is often less common in primary sclerosing cholangitis compared to primary biliary cirrhosis (inflammation and destruction of small bile ducts within the liver).
  • Itching may appear separately or accompany jaundice, which is a sign of advanced bile duct narrowing (usually outside the liver). In addition to yellowing of the skin, changes in urine color and pale stools may be observed. A rapid increase in jaundice indicates the possibility of bile duct cancer development, necessitating urgent diagnosis and treatment.
  • Prolonged bile retention can lead to deficiency in fat-soluble vitamins: A, D, E, and K. These vitamins are essential for the function of normal cells, proteins, fats, carbohydrates, ketones, and many enzyme systems in the body, as well as oxidation-reduction processes and blood clotting.

Classification and Stages of Primary Sclerosing Cholangitis:

There are no universally accepted classifications for primary sclerosing cholangitis, although many attempts have been made to develop them. In recent years, a distinction has been made between large and small bile duct primary sclerosing cholangitis. In small bile duct involvement, typical laboratory signs of bile obstruction and histological features of the disease are present, but no distinct changes in large bile ducts are seen on cholangiography.
Some authors distinguish between primary sclerosing cholangitis associated with inflammatory bowel diseases and those not associated with them.

Complications of Primary Sclerosing Cholangitis:

Complications of primary sclerosing cholangitis can be roughly divided into five groups:

  1. Those resulting from bile duct narrowing: exacerbation of bile obstruction and development of mechanical jaundice.
  2. Long-term complications of obstruction:
  • Steatorrhea (increased fat excretion with stool).
  • Deficiency of fat-soluble vitamins.
  • Osteoporosis: decreased bone strength and structure degradation.
  • Protein and energy deficiency.
  1. Emergence and complications of portal hypertension:
  • Hepatic encephalopathy, where patients develop a liver-like smell from the mouth, become slow and irritable, and behave differently than before.
  • Portal hypertension – high pressure in the portal vein. It usually develops due to liver dysfunction and cirrhosis, but if the veins in this system are compressed for any reason, portal hypertension can occur and be closer.
  • Due to portal hypertension, accumulation (ascites) of free fluid in the abdominal cavity, bleeding from dilated veins in the esophagus, and sudden bacterial peritonitis and others may occur.
  1. Specific complications resulting from infection, such as bacterial cholangitis. This complication usually occurs when strictures form, where the diameter of the common bile duct is less than 1.5 mm, and the right and left hepatic ducts are less than 1 mm. This complication is accompanied by fever and disturbance of consciousness.
  2. Malignant tumors: bile duct cancer and colon cancer.

Diagnosis of Primary Sclerosing Cholangitis:

  1. When alkaline phosphatase levels are elevated in the patient’s blood test, indicating liver injury due to bile flow disorder.
  2. When there are abnormal findings in instrumental examination results.

Laboratory Diagnosis:

  • Chemical blood analysis: Evaluates liver enzyme levels (AST and ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total bilirubin (direct and indirect), albumin, globulin, total cholesterol and fractions, thyroglobulin (TG), creatinine, urea, and glucose. These tests help assess liver function as well as lipid and carbohydrate metabolism.
  • Antibody blood tests: Some tests are conducted to detect antibodies specific to the disease. There are no specific antibodies for primary sclerosing cholangitis, but sometimes the following antibody tests are performed:
  • Anti-neutrophil cytoplasmic antibodies (pANCA), which appear in 26-94% of patients with this disease but may also appear in other conditions (such as autoimmune hepatitis), so a positive pANCA does not indicate a diagnosis of primary sclerosing cholangitis and does not reflect disease prognosis.
  • Immunoglobulin G4 (IgG4), where primary sclerosing cholangitis can be excluded, and a diagnosis of “IgG4-associated sclerosing cholangitis” can be made if the value exceeds four times the upper limit of normal.

Instrumental Diagnosis:

  • Abdominal ultrasound (ultrasound imaging): Helps detect stones in the bile ducts and can show increased portal vein pressure, splenomegaly, and gallbladder enlargement.
  • Computed tomography with contrast media: Can be used in cases suspected of having cholangiocarcinoma, but its sensitivity is low, so the disease may not always be detected.
  • Magnetic resonance cholangiopancreatography (MRCP): A validated examination used to diagnose primary sclerosing cholangitis. Short strictures in the bile ducts inside or outside the liver are shown in the images.

Although the overall diagnostic accuracy of ERCP is higher than magnetic resonance imaging (97% vs. 90%), this test is rarely used because it is considered invasive and carries the risk of complications such as bacterial cholangitis. ERCP is usually performed when a histological examination (biopsy) is needed, i.e., taking a liver tissue sample for histological analysis. In cases of suspected primary sclerosing cholangitis for diagnosis, magnetic resonance imaging is generally sufficient. To prevent bacterial cholangitis after the examination, the doctor may prescribe antibiotics.

(sclerosing cholangitis)
  • Elastography: A special ultrasound-based diagnostic method that allows for the evaluation of liver density. This data can be useful for diagnosing liver fibrosis.
  • Endoscopic retrograde cholangiopancreatography (ERCP): Performed when there is information about liver fibrosis or suspicion of portal vein hypertension. The examination allows for the detection of varices in the esophagus.
Treatment of Primary Sclerosing Cholangitis:
  • Liver transplantation: No medication or treatment can stop or slow down primary sclerosing cholangitis without liver transplantation. Therefore, all other treatment approaches aim to alleviate symptoms and manage complications.
  • Ursodeoxycholic acid: Its use remains controversial, as there is insufficient evidence of long-term benefit. However, ursodeoxycholic acid is considered the primary option in primary sclerosing cholangitis treatment, supported by studies confirming some of its effectiveness.
  • Combination of ursodeoxycholic acid and fibrates (which reduce cholesterol levels): It can be used to treat patients who do not respond to ursodeoxycholic acid alone.
  • Ursodeoxycholic acid with the antibiotic metronidazole: Improves biochemical indicators but does not halt disease progression.
  • Immunotherapy: Does not improve classical disease outcomes, so it is not recommended for use. There is some data on cortisol, prednisone, azathioprine, tacrolimus, methotrexate, mycophenolate mofetil, colchicine, penicillamine, and tumor necrosis factor inhibitors, but the results of these studies are unclear.
  • Traditional therapy: Some drugs, such as sirolimus, show anti-tumor and anti-fibrotic capabilities, but their effectiveness has not been proven.
Symptom and Complication Management:
  • It may be necessary to treat itching, bacterial infections, and vitamin deficiencies.

Outlook and Prevention:


  • There is no way to prevent or reverse the progression of primary sclerosing cholangitis.
  • Treatment focuses on symptom relief and preventing and managing complications, improving quality of life.


  • Currently, there are no specific means to prevent the onset of primary sclerosing cholangitis.
  • Early detection of the disease in its early stages is important for improving prognosis.
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