PRIMARY SCLEROSING CHOLANGITIS

32

Primary sclerosing cholangitis (PSC) is a condition that impacts the bile ducts, which are responsible for transporting bile—a digestive fluid produced by the liver—throughout the body. Bile aids in the breakdown of fats from food and is crucial for digestion.

In PSC, inflammation occurs in the bile ducts, leading to the formation of scars that obstruct the normal flow of bile. As a result, bile accumulates in the liver, causing damage to liver cells and the development of scar tissue within the liver itself.

Over time, this scarring impairs the liver’s ability to function properly, potentially progressing to cirrhosis and eventually liver failure. While PSC can occur at any age, it’s more commonly diagnosed in adults and affects a higher proportion of men than women, with approximately 70% of individuals with PSC being male.

Why is PSC serious?

PSC might not cause problems at first, but it gets worse over time. Here’s why:

• Bile Buildup: Slowed bile flow leads to a buildup in your bile ducts. This trapped bile can leak toxins into your bloodstream, making you feel unwell.
• Liver Damage: The backed-up bile also harms your liver cells. Over time (10-15 years), this damage can lead to liver failure, a life-threatening condition.

Unfortunately, there’s no current cure for PSC. However, doctors can manage the condition and slow down the damage with medications. In severe cases, a liver transplant might be necessary.

Causes

The causes primary sclerosing cholangitis (PSC) can be a bit complex, but it seems to involve a mix of factors:

1. Genetics: There’s evidence suggesting a genetic component to PSC. Certain genetic profiles might make individuals more susceptible to developing the condition.
2. Environmental Factors: Environmental triggers, like exposure to certain toxins, might play a role in initiating an immune response in people with predisposing genetic backgrounds.
3. Immune System Dysfunction: PSC is believed to be linked to autoimmune mechanisms, where the body’s immune system mistakenly attacks its own healthy cells. This chronic inflammation, which is supposed to be a temporary defense mechanism, can become persistent and contribute to the development of the disease.

Doctors have observed that individuals with PSC often have other autoimmune disorders, such as inflammatory bowel diseases, celiac disease, thyroid disease, type 1 diabetes, autoimmune hepatitis, and autoimmune pancreatitis. This association further supports the autoimmune nature of PSC.

Prevalence

• Primary sclerosing cholangitis is considered rare, affecting approximately 1 to 16 individuals per 100,000 people.
• It is more common in men than in women, and typically diagnosed between the ages of 30 and 50.

Symptoms

Early on, PSC might not show any noticeable symptoms, and it’s often incidentally discovered during tests for other conditions. However, as the disease progresses, symptoms may become apparent. Initially, these symptoms may be vague and include:

• Fatigue: Feeling unusually tired or lacking energy.
• Upper Right Quadrant Abdominal Pain: Discomfort or pain in the upper right side of the abdomen.
• Itchy Skin (Pruritus): Persistent itching, often without any visible rash.

In later stages, as the disease advances, symptoms can become more pronounced and may include:

• Swollen Abdomen: Abdominal swelling or bloating.
• Enlarged Liver: The liver may become larger than normal.
• Enlarged Spleen: Similarly, the spleen may also enlarge.
• Jaundice: Yellowing of the skin and whites of the eyes due to liver dysfunction.
• Fever: Elevated body temperature, indicating inflammation or infection.
• Unintended Weight Loss: Losing weight without trying to do so.

Risk Factors

• While the exact risk factors for PSC are not well-defined, certain factors may increase the likelihood of developing the condition, including a family history of PSC or other autoimmune diseases, such as inflammatory bowel disease (IBD), particularly ulcerative colitis.

Diagnosis

Diagnosing primary sclerosing cholangitis (PSC) can be tricky since it’s often stumbled upon incidentally during tests for unrelated issues. Surprisingly, up to half of individuals diagnosed with PSC may not exhibit any symptoms initially.

Early indications of PSC may surface through routine blood tests or imaging studies. Distinctive features on images of bile ducts can raise suspicion for PSC. Moreover, certain blood markers, such as elevated levels of alkaline phosphatase or specific antibodies associated with immune responses in the bile ducts, might be observed. An increase in white blood cell count could also signal an infection in the liver.

To confirm a diagnosis, your healthcare provider might recommend further, more specific tests, including:

1. Liver Function Test: This involves analyzing blood samples for heightened levels of specific liver enzymes, with elevated alkaline phosphatase levels potentially indicating PSC.
2. Magnetic Resonance Cholangiopancreatography (MRCP): MRCP employs magnetic resonance imaging (MRI) to generate detailed images of the biliary tree, encompassing the liver, gallbladder, and bile ducts. It’s often the preferred imaging method for diagnosing PSC due to its non-invasive nature and avoidance of radiation exposure. However, in some cases, MRCP might not detect early or mild instances of the disease, necessitating alternative imaging techniques.

Treatments

There is no cure for primary sclerosing cholangitis, but treatment aims to manage symptoms, slow disease progression, and prevent complications.

Managing primary sclerosing cholangitis (PSC) focuses on addressing symptoms and complications since there’s currently no treatment to halt its progression. Here’s how healthcare providers typically approach treatment:

1. Symptom Management:
   • Itchy Skin (Pruritus): Medications may be prescribed to alleviate itching.
   • Vitamin Deficiencies: Supplements may be recommended to address deficiencies in vitamins, particularly fat-soluble ones.
   • Infections: Antibiotics are used to treat infections that may arise due to blocked bile ducts.
2. Surveillance and Intervention:
   • Regular monitoring of liver function and bile duct health is essential to track disease progression.
   • Periodic interventions may be performed to alleviate blockages in the bile ducts. This can be done through procedures like endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous trans-hepatic cholangiography (PTHC), where specialized instruments are used to open up blocked ducts or place stents to maintain patency.
3. Liver Transplantation:
   • As PSC progresses, ultimately leading to liver failure over 10 to 20 years, liver transplantation becomes necessary.
   • Healthcare providers closely monitor liver damage to determine the appropriate timing for transplantation.
   • Individuals must meet specific criteria to be placed on the liver transplantation waiting list.

While interventions like ERCP or PTHC offer temporary relief, the ultimate goal for individuals with advanced PSC is liver transplantation. However, it’s crucial to acknowledge that even after transplantation, PSC can recur in some cases, impacting the longevity of the new liver.

Navigating PSC involves a multidisciplinary approach, with healthcare providers collaborating to manage symptoms, monitor disease progression, and provide supportive care. Regular communication with healthcare teams and adherence to treatment plans are vital for optimizing outcomes and maintaining quality of life for individuals living with PSC.

• Medications such as ursodeoxycholic acid (UDCA) may be prescribed to improve liver function and bile flow.
• In some cases, procedures such as balloon dilation or stent placement may be performed to open narrowed or blocked bile ducts.
• Liver transplantation may be considered for individuals with advanced PSC and liver failure.

Home Care Tips

Living with PSC involves taking proactive steps to manage symptoms and maintain overall health. Here are some lifestyle recommendations to consider:

• Avoid Alcohol and smoking: Alcohol and smoking can exacerbate liver damage, so it’s best to abstain from alcohol and smoking consumption entirely.
• Healthy Eating: Focus on consuming a balanced diet rich in whole foods and low in processed foods to support liver health.
• Stress Management: Practice stress-reduction techniques such as mindfulness, meditation, or relaxation exercises to minimize the impact of stress on your health.
• Adequate Sleep: Prioritize getting enough sleep each night to support overall well-being and energy levels.
• Regular Exercise: Engage in regular physical activity, even if it’s just a little each day. Exercise can help combat fatigue and improve overall fitness levels.
• Manage itching: Treat itching with over-the-counter antihistamines or topical creams recommended by your healthcare provider.

Complications of advanced PSC

As primary sclerosing cholangitis (PSC) progresses, it can lead to various complications due to the increasing scarring of the bile ducts and liver. Here are some of the potential complications of advanced PSC:

1. Metabolic Diseases: When bile ducts become severely blocked, they fail to deliver bile to the small intestine for digestion, leading to difficulties in processing fats and absorbing fat-soluble vitamins (A, D, E, and K). This can result in:
   • Fatty stools and diarrhea.
   • Malabsorption of nutrients and malnutrition.
   • Easy bruising and bleeding due to vitamin K deficiency.
   • Bone conditions like osteomalacia and osteoporosis due to vitamin D deficiency.
   • Impaired night vision.
2. Portal Hypertension: Progressive cirrhosis of the liver reduces blood flow through the liver, increasing pressure in the portal vein within the digestive system. Elevated pressure in this vein can cause enlargement of other veins in the esophagus and abdomen, making them prone to rupture and leading to internal bleeding.
3. Infections: Blocked bile ducts are susceptible to frequent infections, which can manifest as fever, abdominal pain, blood infection, or sepsis.
4. Cancer Risk: Advanced PSC significantly increases the risk of developing various cancers, including:
   • Bile duct cancer (cholangiocarcinoma), with a risk ranging from 5% to 20%.
   • Gallbladder cancer.
   • Liver cancer (hepatoma).
   • Colorectal cancer, particularly if inflammatory bowel disease (IBD) coexists.

Prevention

Since the exact cause of primary sclerosing cholangitis is unknown, there are no specific preventive measures. However, managing underlying conditions such as IBD may help reduce the risk of developing PSC.

Primary sclerosing cholangitis (PSC) Vs. Secondary sclerosing cholangitis (SSC)

Here’s a breakdown of the key differences between primary sclerosing cholangitis (PSC) and secondary sclerosing cholangitis (SSC):

Primary vs. Secondary Cause:

• PSC: The inflammation and scarring (sclerosis) of bile ducts is the original disease itself. There’s no underlying cause.
• SSC: The inflammation and scarring are secondary effects caused by something else, such as bile duct injury, infections, chemotherapy, gallstones, or recurring pancreatitis.

Location of Damage:

• PSC: Can affect bile ducts both inside (intrahepatic) and outside (extrahepatic) the liver.
• SSC: Damage is typically limited to the bile ducts.

Other Differences:

• Gender: PSC is more common in males, while SSC doesn’t have a strong gender bias.
• Inflammatory Bowel Disease (IBD): PSC is highly associated with pre-existing IBD, especially ulcerative colitis. SSC has no such link.
• Cancer Risk: PSC carries an increased risk of bile duct cancer, whereas SSC does not.
• Treatment: UDCA medication can help slow the progression of PBC. Currently, there’s no specific medical treatment for PSC, although managing underlying conditions that caused SSC can be helpful.

Similarities:

Both PSC and SSC are progressive diseases that damage bile ducts, leading to bile buildup, liver damage, and potentially cirrhosis.

When to See a Doctor

If you experience persistent symptoms such as abdominal pain, fatigue, or jaundice, it is important to consult your healthcare provider for proper evaluation and diagnosis.

Outlook/Prognosis

After diagnosis, the average life expectancy typically ranges from 10 to 20 years. However, it’s essential to note that this is an average, and individual outcomes can vary widely.

For those with PSC, a liver transplant can offer a new chance at life. However, in around 15% to 20% of cases, PSC may recur after transplantation. If this happens, the new liver may fail, leading to an average life expectancy of about nine months in such cases.

Another significant factor influencing life expectancy is the development of cancer as a complication of PSC. If cancer arises, individuals may not be suitable candidates for a liver transplant. In select cases, healthcare providers may opt to treat cancer first using methods like radiation or chemotherapy before considering a liver transplant.

Sources

1. Mayo Clinic. “Primary Sclerosing Cholangitis.”
2. National Institute of Diabetes and Digestive and Kidney Diseases. “Primary Sclerosing Cholangitis.”
3. Liver Foundation. “Primary Sclerosing Cholangitis (PSC).” R
4. GARD. Primary sclerosing cholangitis 
5. Marchioni Beery RM, Vaziri H, Forouhar F. Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis: a Review Featuring a Women’s Health Perspective 
6. MedlinePlus. Primary sclerosing cholangitis 
7. Merk Manual Consumer Version. Primary Sclerosing Cholangitis
8. NIH. Primary Sclerosing Cholangitis
9. PSCpartners.org. PSC and PBC 
10. Clevland Clinic
11. European Association for the Study of the Liver (EASL). “EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary sclerosing cholangitis.” Journal of Hepatology, Volume 51, Issue 2, Pages 398-409.
12. Lindor, K. D., Kowdley, K. V., Harrison, M. E. “ACG Clinical Guideline: Primary Sclerosing Cholangitis.” American Journal of Gastroenterology, Volume 113, Pages 1490-1494.