Primary Sclerosing Cholangitis: Causes, Risk Factors, Symptoms, Diagnosis, Treatment and Associated Diseases

It is the chronic inflammation of the bile ducts.

Scars and thickening of tissue in the ducts can narrow the channel through which bile flows, leading to cirrhosis and liver damage .

The bile ducts are important because they allow bile to drain out of the liver.

In primary sclerosing cholangitis, the bile ducts inside and outside the liver become inflamed and scarred.

The ducts become blocked as scarring increases, leading to cholestasis , or stopping of bile flow.

The formation of bile is one of the functions of the liver.

Bile is a liquid that contains water, certain minerals that carry an electrical charge (electrolytes), and other materials including bile salts, phospholipids, cholesterol, and a yellow-orange pigment, called bilirubin, which is a by-product of natural breakdown. of hemoglobin.

The flow of bile serves two important tasks within the body:

  • Helps with digestion and absorption of fats, vitamins, and other nutrients from the diet.
  • Helps remove excess cholesterol, bilirubin, waste, and toxins from the body.

Therefore, a problem with normal bile flow often results in poor absorption of vital nutrients and the accumulation of toxic materials in the body.

Bile trapped in the liver damages liver cells and eventually causes liver failure.

Causes of primary sclerosing cholangitis

Primary sclerosing cholangitis is a multifactorial disorder, which means that several different factors such as genetic, environmental, and immunological that occur in combination are necessary for the development of the disorder.

The specific factors involved in the development of primary sclerosing cholangitis have not been conclusively identified.

Researchers believe that the disorder is due to a nonspecific triggering event that causes an abnormal response of the immune system.

Specifically an abnormal inflammatory or allergic reaction (immune disorder) or because the immune system mistakenly attacks healthy tissue (autoimmunity) in people who are genetically susceptible to such a reaction.

This abnormal response eventually causes progressive damage to the bile ducts.

The triggering event is most likely an infectious or toxic agent.

Genetics play an important role in the development of primary sclerosing cholangitis, and the incidence of the disorder among first-degree relatives, especially siblings, is higher than might be expected.

Researchers have discovered sixteen different genetic regions that are associated with the disorder.

Certain genes in these genetic areas can predispose affected individuals to develop primary sclerosing cholangitis.

A genetic predisposition means that a person carries a gene or genes for a disease, but may not be expressed unless something in the environment triggers the disease.

Some, but not all, of these genetic regions involve a genetically determined human leukocyte antigen.

Human leukocyte antigens are proteins that play an important role in the body’s immune system.

Several of the genetic areas associated with primary sclerosing cholangitis are also associated with inflammatory bowel disease.

More research is needed to understand the underlying cause and the various mechanisms that ultimately result in the development of primary sclerosing cholangitis, and to create a classification system that defines specific subtypes of the disorder.

Risk factors for primary sclerosing cholangitis

Primary sclerosing cholangitis is a rare disorder that occurs in approximately 20 to 60 of every million people.

It affects both men and women, but is more common in men, at a ratio of 2: 1.

Although it can affect people of any age, the disorder occurs most often in middle-aged adults.

It is also increasingly recognized in children and babies.

Symptoms of primary sclerosing cholangitis

Primary sclerosing cholangitis is characterized by episodes of interrupted or obstructed bile flow from the liver (cholestasis), resulting from inflammation, thickening, and / or abnormal formation of fibrous tissue (fibrosis) within the bile ducts.

The specific symptoms, progression, and severity of primary sclerosing cholangitis can vary greatly from one individual to another.

Initially, many affected people may have no noticeable symptoms (asymptomatic) or only have mild symptoms.

Some people will only show mild symptoms for many years.

Common initial symptoms of primary sclerosing cholangitis are fatigue, abdominal discomfort, and itching ( pruritus ).

The itching can be potentially serious and can even be disabling.

When the flow of bile from the liver is blocked, the bile can be absorbed into the bloodstream, causing the skin, mucous membranes, and the whites of the eyes to turn yellow ( obstructive jaundice ).

Additional symptoms include a general ill feeling, abdominal pain especially in the upper right portion of the abdomen, nausea, dark urine, light colored stools involuntary weight loss, abnormal enlargement of the liver (hepatomegaly) and spleen ( splenomegaly ) .

Some people may develop deficiencies in certain vitamins, including vitamins A, D, E, and K.

These are fat soluble vitamins. Bile normally helps break down fat so these vitamins can be absorbed by the body.

Some people with chronic liver disease develop metabolic bone disease, which may be called hepatic osteodystrophy.

Affected people can eventually develop osteoporosis , a condition in which the bones become very brittle.

People with osteoporosis are prone to repeated fractures.

In severe cases, fractures can occur even from mild stress, such as coughing.

The bones in the wrist, hips, and spine are often affected.

In some cases, affected individuals may experience episodes of fever, chills, and night sweats as a result of bile duct infection (bacterial cholangitis).

Primary sclerosing cholangitis can progress and cause scarring and damage to the liver (cirrhosis) and increased blood pressure in the veins that carry blood from the gastrointestinal tract to the heart through the liver (portal hypertension).

Portal hypertension can lead to serious complications, such as:

  • Accumulation of fluid in the stomach ( ascites ).
  • Bleeding from the blood vessels within the esophagus, stomach, and rectum.
  • Hepatic encephalopathy, a brain disorder that ranges from a subtle condition with no external signs or symptoms to a serious condition that can cause serious complications, such as confusion and coma.

As people with primary sclerosing cholangitis age, they often develop life-threatening complications, such as liver failure.

People with primary sclerosing cholangitis are at higher risk than the general population of developing a form of cancer that affects the bile ducts (cholangiocarcinoma).

Approximately 8 to 15% of affected individuals eventually develop cholangiocarcinoma.

Affected people are also at risk of developing gallbladder cancer.

Individuals with primary sclerosing cholangitis also have ulcerative colitis, an inflammatory bowel disease of unknown cause characterized by chronic inflammation and ulceration of the lining of the main portion of the large intestine (colon).

Primary sclerosing cholangitis is also associated with Crohn’s disease , another form of inflammatory bowel disease.

These conditions can be mild or even “silent”, with no apparent symptoms (asymptomatic).

People with primary sclerosing cholangitis or Crohn’s disease have a higher risk of developing colon cancer compared to people with one of these conditions or the general population.

In addition to inflammatory bowel disease, numerous autoimmune or immune disorders have been reported to be associated with primary sclerosing cholangitis.

Such disorders include sarcoidosis, thyroid disease, Peyronie’s disease, retroperitoneal fibrosis, psoriasis, rheumatoid arthritis , celiac disease, Sjogren’s syndrome , chronic pancreatitis, diabetes mellitus, Wegener’s granulomatosis, pyoderma gangrenosum, Grave’s disease, Langerhans.

The exact relationship between these disorders and primary sclerosing cholangitis is as yet unknown.

Primary sclerosing cholangitis may develop as a secondary condition to some of these disorders.

Diagnosis of primary sclerosing cholangitis

The symptoms of primary sclerosing cholangitis can be due to other disorders, so an accurate diagnosis is essential to ensure that you receive the most effective care.

Diagnosis is made by blood tests and a special type of MRI of the liver that studies the bile ducts. This test is done without contrast agents.

The imaging tests recommended by the doctor are usually:

Endoscopic ultrasound

The use of a special high-energy sound wave endoscope (“echoendoscope”) to view the digestive tract and nearby organs.

Probe-based endomicroscopy

It is a highly specialized approach, involving the use of a small microscope to evaluate the narrowing of the bile ducts.

Narrowband images

With this endoscopic technique, a special system is used to capture high-resolution images of the bile ducts without the use of dyes.

It is based on the fact that light of different wavelengths penetrates the tissue at different depths and can be used to see the fine characteristics of the lining (mucosa) of the bile ducts.

Magnetic resonance cholangiopancreatography

MRI is used to produce detailed cross-sectional images of organs and other digestive tissues.

In approximately 10% of patients, the affected bile ducts are too small to be seen by MRI imaging and a liver biopsy is necessary to localize the disease.

Liver biopsy

The doctor takes a small sample of liver tissue to examine it for cirrhosis and other damage.

Endoscopic retrograde cholangiopancreatography

An endoscopist guides an endoscope through the mouth into the bile ducts, releases a dye that helps images and then X-rays.

If necessary, a smaller scope can be used to directly view the bile ducts and help provide biopsies.

Bile duct tissue can be tested to determine if a patient is at increased risk of developing cancer.

Treatment for primary sclerosing cholangitis

At this time, no medications have proven to be a successful cure for primary sclerosing cholangitis.

Treatment of primary sclerosing cholangitis focuses primarily on managing symptoms and slowing the progression of the disease.

Lost vitamins must be replaced when necessary to prevent complications related to these deficiencies.

Antibiotics can be helpful in controlling inflammation or infection.

People with primary sclerosing cholangitis are advised to eat a normal, healthy diet and avoid alcohol.

Some medications are used for early primary sclerosing cholangitis.

Doctors may prescribe cholestyramine (Questran) to relieve itching, which works by reducing the level of bile acids in the blood and skin.

Ursodeoxycholic acid, a naturally occurring bile acid drug, has been studied to increase bile flow and reduce bile duct inflammation in the early stages of the disease.

Ursodeoxycholic acid has no side effects and has also been used in the treatment of gallstones with a probable benefit.

In some cases, surgery is needed to open the blockages in the common bile duct.

An interventional endoscopist can insert a miniature balloon and stent (small tube) into a narrowed area to reopen a blocked bile duct, restore function, and reduce symptoms of the disease.

Endoscopic surgery to remove obstructions and enlarge narrowed bile ducts can be beneficial in helping to prevent deterioration of the liver in certain cases.

It is extremely important to carry out regular tests to monitor the progress of the disease and to verify that tumors are not forming.

If the treatment of primary sclerosing cholangitis is no longer effective and severe liver failure occurs, it is necessary to prepare the patient for a liver transplant.

The survival rate for this procedure in people with primary sclerosing cholangitis is usually 75 percent or more, and patients experience a good quality of life after recovery.

A variety of liver transplant approaches, including living donor liver transplantation, are used to push the boundaries of organ transplantation and provide as many transplants as possible.

Associated diseases

Associated diseases are extremely important, especially inflammatory bowel diseases that affect 80% of people with primary sclerosing cholangitis.

Inflammation of the intestine, which may not cause any discomfort, should always be looked for by endoscopic examinations.

In fact, if the intestine is inflamed, the liver will also be inflamed.

On the other hand, if the inflammation of the intestine is controlled by the various medications available, the inflammation of the liver is also reduced.