Primary sclerosing cholangitis is a condition that affects the bile ducts. These ducts carry bile (a fluid that helps to digest fats) from the liver, where bile is produced, to the gallbladder, where it is stored, and to the small intestine, where it aids in digestion. Primary sclerosing cholangitis occurs because of inflammation in the bile ducts (cholangitis) that leads to scarring (sclerosis) and narrowing of the ducts. As a result, bile cannot be released to the gallbladder and small intestine, and it builds up in the liver.

Primary sclerosing cholangitis is usually diagnosed around age 40, and for unknown reasons, it affects men twice as often as women. Many people have no signs or symptoms of the condition when they are diagnosed, but routine blood tests reveal liver problems. When apparent, the earliest signs and symptoms of primary sclerosing cholangitis include extreme tiredness (fatigue), discomfort in the abdomen, and severe itchiness (pruritus). As the condition worsens, affected individuals may develop yellowing of the skin and whites of the eyes (jaundice) and an enlarged spleen (splenomegaly). Eventually, the buildup of bile damages the liver cells, causing chronic liver disease (cirrhosis) and liver failure. Without bile available to digest them, fats pass through the body. As a result, weight loss and shortages of vitamins that are absorbed with and stored in fats (fat-soluble vitamins) can occur. A fat-soluble vitamin called vitamin D helps absorb calcium and helps bones harden, and lack of this vitamin can cause thinning of the bones (osteoporosis) in people with primary sclerosing cholangitis.

Primary sclerosing cholangitis is often associated with another condition called inflammatory bowel disease, which is characterized by inflammation of the intestines that causes open sores (ulcers) in the intestines and abdominal pain. However, the reason for this link is unclear. Approximately 70 percent of people with primary sclerosing cholangitis have inflammatory bowel disease, most commonly a form of the condition known as ulcerative colitis. In addition, people with primary sclerosing cholangitis are more likely to have an autoimmune disorder, such as type 1 diabetes, celiac disease, or thyroid disease, than people without the condition. Autoimmune disorders occur when the immune system malfunctions and attacks the body's tissues and organs. People with primary sclerosing cholangitis also have an increased risk of developing cancer, particularly cancer of the bile ducts (cholangiocarcinoma).

Primary sclerosing cholangitis (PSC) is a chronic liver disease in which the bile ducts inside and outside the liver become inflamed and scarred, and are eventually narrowed or blocked. When the bile ducts are narrowed or blocked, bile builds up in the liver and causes further liver damage. This damage can lead to cirrhosis and, eventually, liver failure. Medical experts believe PSC is an autoimmune disease, in which the immune system attacks normal, healthy bile duct cells.

An estimated 1 in 10,000 people have primary sclerosing cholangitis, and the condition is diagnosed in approximately 1 in 100,000 people per year worldwide.

People with PSC may have other health problems, including

• IBD
• gallstones
• autoimmune hepatitis
• other autoimmune diseases, such as type 1 diabetes, celiac disease, and thyroid diseases

About 7 out of 10 people who have PSC also have IBD.

PSC is more commonly diagnosed in people who

• are between the ages of 30 and 40, although PSC may occur at any age.
• are male. PSC affects twice as many males as females.
• have inflammatory bowel disease (IBD), most commonly ulcerative colitis.

Primary sclerosing cholangitis is thought to arise from a combination of genetic and environmental factors. Researchers believe that genetic changes play a role in this condition because it often occurs in several members of a family and because immediate family members of someone with primary sclerosing cholangitis have an increased risk of developing the condition. It is likely that specific genetic variations increase a person's risk of developing primary sclerosing cholangitis, and then exposure to certain environmental factors triggers the disorder. However, the genetic changes that increase susceptibility and the environmental triggers remain unclear.

There is evidence that variations in certain genes involved in immune function influence the risk of developing primary sclerosing cholangitis. The most commonly associated genes belong to a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Each HLA gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. Specific variations of several HLA genes seem to be present more often in people with primary sclerosing cholangitis than in people who do not have the disorder. These variations may dysregulate the body's immune response, leading to the inflammation of the bile ducts in people with primary sclerosing cholangitis. However, the mechanism is not well understood. Researchers are also studying variations in other genes related to the body's immune function to understand how they contribute to the risk of developing this condition.

The inheritance pattern of primary sclerosing cholangitis is unknown because many genetic and environmental factors are likely to be involved. This condition tends to cluster in families, however, and having an affected family member is a risk factor for developing the disease.

Symptoms of primary sclerosing cholangitis (PSC) may include

• pain in the abdomen, or belly
• itchy skin
• diarrhea
• yellowish color of the whites of the eyes and skin, called jaundice
• feeling tired or weak
• fever

PSC may lead to a bile duct infection. Symptoms of a bile duct infection include

• chills
• fever
• new or worsening jaundice
• pain in the upper right side of the abdomen

As the disease gets worse, you may develop cirrhosis. Symptoms of cirrhosis may include

• swelling of the abdomen from a buildup of fluid, called ascites
• confusion or difficulty thinking caused by a buildup of toxins in the brain, called hepatic encephalopathy
• gastrointestinal bleeding caused when enlarged veins—called varices—burst in the esophagus, stomach, or intestines
• other symptoms of cirrhosis, such as edema, jaundice, and weight loss

Because PSC gets worse slowly, you can have the disease for years before you have any symptoms. Many people have no symptoms when they are first diagnosed with PSC.

PSC can lead to liver complications such as cirrhosis, cancers, and bile duct infection.

Liver complications

PSC can damage the liver, leading to cirrhosis and its complications.

Cirrhosis

In cirrhosis, scar tissue replaces healthy liver tissue and prevents your liver from working normally. As cirrhosis gets worse, the liver begins to fail.

Portal hypertension

Portal hypertension most often occurs when scar tissue in the liver slows the normal flow of blood, which causes high blood pressure in the portal vein. The portal vein is the large blood vessel that carries blood from your stomach, intestines, spleen, gallbladder, and pancreas to the liver.

When portal hypertension reaches a certain level, it can cause additional complications, such as

• swelling in the legs, ankles, or feet, called edema
• buildup of fluid in the abdomen, called ascites
• enlarged veins—called varices—in the esophagus, stomach, or intestines, which can lead to gastrointestinal bleeding if the veins burst
• confusion or difficulty thinking caused by a buildup of toxins in the brain, called hepatic encephalopathy

Liver failure

Cirrhosis may eventually lead to liver failure, also called end-stage liver disease. With liver failure, your liver is badly damaged and stops working. People with liver failure may require a liver transplant.

Cancer

PSC can increase the chance of developing certain cancers.

• Bile duct cancer is the most common type of cancer in people who have PSC. People with PSC have a 10% to 20% chance of developing bile duct cancer at some point in their lives.
• People with PSC have an increased chance of getting gallbladder cancer.
• People with cirrhosis due to PSC have an increased chance of getting liver cancer.
• People with PSC and IBD have an increased chance of getting colorectal cancer.

Bile duct infection

People with PSC may develop a bacterial infection in narrowed or blocked bile ducts. Medical procedures that affect the bile ducts, such as endoscopic retrograde cholangiopancreatography, increase the chance of bile duct infection.

Other complications

Other complications of PSC may include

• low levels of fat-soluble vitamins A, D, E, and K
• osteoporosis, or loss of calcium from the bones

Doctors diagnose primary sclerosing cholangitis (PSC) based on medical and family history, a physical exam, and the results of medical tests.

Medical and family history

The doctor will ask about your symptoms. He or she may also ask whether you have

• a history of inflammatory bowel disease (IBD), particularly ulcerative colitis
• a parent or sibling who has PSC or IBD
• a personal or family history of autoimmune diseases, such as autoimmune hepatitis, type 1 diabetes, celiac disease, and thyroid diseases

Physical exam

Your doctor will examine your body, including your abdomen. He or she will check for

• signs of cirrhosis and liver failure, such as jaundice, which can make the whites of the eyes and skin look yellow
• scratch marks from scratching itchy skin
• signs that the liver and spleen are larger than they should be
• tenderness or pain in the abdomen

Blood tests

A health care professional will take a blood sample from you and send the sample to a lab.

Liver tests can show abnormal levels of liver enzymes and other substances in your blood. Abnormal levels of certain liver enzymes may be a sign your liver or bile ducts are damaged.

Imaging tests

To diagnose PSC, doctors typically order a special imaging test to examine the bile ducts, such as

• magnetic resonance cholangiopancreatography (MRCP), which uses a magnetic resonance imaging (MRI) machine to create pictures of the bile ducts. MRCP is the most common test that doctors use to diagnose PSC.
• endoscopic retrograde cholangiopancreatography (ERCP), which combines upper gastrointestinal (GI) endoscopy and x-rays to examine the bile and pancreatic ducts. Doctors may also use ERCP to treat narrowed bile ducts.
• percutaneous transhepatic cholangiography (PTC), which is an x-ray of the bile ducts. A health care professional inserts a needle through the skin and into the liver to inject a special dye into the bile ducts. The special dye lets a doctor see the bile ducts on the x-ray.

Doctors may also order other imaging tests to check for signs of PSC, other bile duct or liver problems, or complications. These tests include

• ultrasound, which uses a hand-held device, called a transducer, that bounces safe, painless sound waves off organs to create an image of their structure.
• computed tomography (CT) scans, which uses a combination of x-rays and computer technology to create images of the liver.
• elastography, a special test that measures the stiffness of the liver. Increased liver stiffness may be a sign of fibrosis, or scarring.

Liver biopsy

A liver biopsy is generally not needed to diagnose PSC. However, in some cases, doctors may order a liver biopsy to check for signs of other liver diseases, such as autoimmune hepatitis.

During a liver biopsy, a doctor will take small pieces of tissue from the liver. A pathologist will examine the tissue under a microscope.

Colonoscopy

For people who have PSC and haven’t already been diagnosed with IBD, doctors may recommend a colonoscopy to check for IBD. Many people with PSC have mild IBD and don’t have IBD symptoms.

Currently, no cure or effective treatments for primary sclerosing cholangitis (PSC) exist. However, doctors can treat narrowed or blocked bile ducts and symptoms of PSC.

Narrowed or blocked bile ducts

If bile ducts are narrowed or blocked, doctors may use endoscopic retrograde cholangiopancreatography (ERCP) to open them and help keep them open. To help keep ducts open, doctors sometimes place stents. Stents are tiny tubes that a doctor leaves in narrowed ducts for a short time to hold them open.

In some cases, doctors may use percutaneous transhepatic cholangiography to open narrowed or blocked bile ducts.

Itchy skin

Doctors may recommend over-the-counter medicines or prescribe medicines to treat itchy skin caused by PSC.

Liver complications

Doctors may recommend treatments for liver complications of PSC.

Cirrhosis or portal hypertension

If PSC leads to cirrhosis or portal hypertension, doctors can treat the health problems related to these conditions with medicines, medical procedures, or surgery.

Liver failure

If cirrhosis leads to liver failure, you may need a liver transplant.

Cancer

PSC increases the risk for developing several types of cancer. Your doctor may recommend tests to check for signs of cancer. Finding cancer at an early stage improves the chance of curing the cancer.

• For adults with PSC, doctors may suggest imaging tests and blood tests to check for bile duct cancer and gallbladder cancer.
• For people with cirrhosis caused by PSC, doctors may suggest blood tests and an ultrasound or another type of imaging test to check for liver cancer.
• For people with PSC and inflammatory bowel disease, doctors may suggest a colonoscopy to check for colorectal cancer.

Bile duct infection

To treat a bile duct infection, doctors may prescribe antibiotics. To help prevent bile duct infections, doctors may prescribe antibiotics for people with PSC before and after they have procedures, such as ERCP, that increase the risk of getting an infection.

Other complications

Doctors may treat other complications of PSC with medicines, dietary supplements, or changes in diet or lifestyle.

• For low levels of vitamins A, D, E, and K, doctors may recommend taking dietary supplements of these fat-soluble vitamins. Follow your doctor’s instructions on the type and amount of vitamins you should take.
• For osteoporosis, doctors may prescribe medicines that slow or stop bone loss and improve bone density. Doctors may recommend taking dietary supplements of calcium and vitamin D.

Doctors may consider a liver transplant if PSC leads to liver failure or causes severe symptoms or complications. In some patients with bile duct cancer, liver transplant may be the best treatment. Doctors consider liver transplants only after all other treatment options have failed. Talk with your doctor to find out whether a liver transplant is right for you.

If you have PSC, you can take steps to help prevent further liver damage.

• Follow your doctor’s instructions carefully and take medicines and dietary supplements as directed.
• Quit smoking.
• Do not use illegal drugs.
• Stop drinking alcohol or, at least, limit your intake. If you have PSC and cirrhosis, completely stop drinking alcohol.
• Have regular checkups, as recommended by your doctor.
• Talk with your doctor before taking
  • over-the-counter medicines.
  • dietary supplements.
  • complementary and alternative medicines.
• Try to reach and stay at a healthy body weight.

People with primary sclerosing cholangitis (PSC) should eat a healthy, well-balanced diet. Good nutrition is important in all stages of PSC—including cirrhosis—to help the liver work properly and manage complications.

Your doctor can recommend a healthy diet that provides enough calories and nutrients. Your doctor may recommend taking dietary supplements of calcium and vitamin D to help prevent osteoporosis. For low levels of fat-soluble vitamins A, D, E, or K, your doctor may recommend taking supplements of these vitamins. Follow your doctor’s instructions on the type and amount of vitamins you should take.

You should avoid eating raw or undercooked shellfish, fish, meat, and unpasteurized milk. Bacteria or viruses from these foods may cause severe infections in people with liver disease.

Doctors may recommend that people with PSC stop drinking alcohol or, at least, limit their intake. People who have PSC and cirrhosis should completely stop drinking alcohol.