What is Primary Sclerosing Cholangitis?
Primary sclerosing cholangitis (PSC) is a disease that gradually worsens over time, causing harm to the liver. Its causes are not known. PSC is characterized by inflammation, scarring, and narrowing of the liver’s internal and/or external bile ducts. Without a liver transplant, people diagnosed with PSC generally survive about ten years.
There are different types of PSC:
1. Classic PSC: This type affects both small and large bile ducts.
2. Small-duct PSC: This only impacts small bile ducts.
3. PSC associated with autoimmune hepatitis: This affects both small and large bile ducts.
PSC is associated with a digestive disease called ulcerative colitis and can lead to a type of liver cancer called cholangiocarcinoma. Recently, the use of a diagnostic technique called endoscopic retrograde cholangiopancreatography (ERCP) has made it easier to recognize this condition. There’s currently no cure for PSC, but it can be managed with a drug called ursodeoxycholic acid. Some people need a liver transplant, but then they have to cope with a weakened immune system and the problems that can cause.
What Causes Primary Sclerosing Cholangitis?
We don’t fully understand the causes of primary sclerosing cholangitis, but we know that both genetic and environmental factors play a role in its development. A significant risk factor for this condition is inflammatory bowel disease (IBD). In fact, 60% to 80% of patients with primary sclerosing cholangitis also have IBD, most commonly ulcerative colitis. Additionally, 5% to 10% of patients with ulcerative colitis also have primary sclerosing cholangitis.
It’s thought that primary sclerosing cholangitis is an autoimmune disorder, which is a condition in which the body’s immune system mistakenly attacks healthy cells. In some patients, the levels of certain antibodies (proteins that the immune system uses to fight off bacteria and viruses) are higher than normal. Furthermore, individuals with certain genes called HLA B8 and HLA DR3 have a higher risk of developing this disorder.
Risk Factors and Frequency for Primary Sclerosing Cholangitis
Primary sclerosing cholangitis is a disease that is not very common overall, with the number of new cases each year and current cases ranging from 0 to 1.3 and 0 to 16.2 per 100,000 people, respectively. Compared to Asia, the incidence of this disease is higher in North America and Northern Europe.
Most people are diagnosed with this disease between the ages of 30 and 40, and it’s more commonly found in men. In fact, men have twice the risk of developing this disease compared to women. Also, individuals who have siblings with this disease are 9 to 39 times more likely to get it compared to the general population. Interestingly, it is often found in people who do not smoke.
- Primary sclerosing cholangitis affects between 0 and 1.3 people per 100,000 each year.
- Current cases range from 0 to 16.2 per 100,000 people.
- The disease is more common in North America and Northern Europe compared to Asia.
- People are typically diagnosed between the ages of 30 and 40.
- Men are more likely to develop the disease, with a risk twice that of women.
- Having a sibling with the disease increases one’s risk by 9 to 39 times compared to the general population.
- The disease is commonly observed in nonsmokers.
Signs and Symptoms of Primary Sclerosing Cholangitis
Primary sclerosing cholangitis is a liver condition that often shows no symptoms in about half of the patients. Many times, it’s diagnosed when abnormal liver function tests are conducted for unrelated reasons. It predominantly affects men who are in their 30s or 40s.
When symptoms do appear, patients can experience a variety of discomforts. These include:
- Pain in the upper right quarter of the abdomen (20% of patients)
- Intense and potentially disrupting itching, also known as pruritus (10%)
- Fatigue
- Yellowing of the skin and eyes, known as jaundice (6%)
- Weight loss
More serious signs of advanced liver disease can develop over time as well: jaundice, gastrointestinal bleeding, fluid accumulation in the abdomen (ascites), and confusion.
On physical examination, doctors may find that the liver is enlarged (a condition called hepatomegaly) in 44% of patients, or that the spleen has swelled (splenomegaly) in 39% of patients. They might also notice jaundice and skin scratch marks caused by severe itching.
If a patient develops fever, chills, and upper right abdominal pain—with or without jaundice—it may signal a sporadic occurrence of bacterial cholangitis, a type of infection.
Testing for Primary Sclerosing Cholangitis
Liver tests typically show a certain pattern – called a cholestatic pattern – for people with this disease. A common finding is a high level of serum alkaline phosphatase in the blood. Other components such as aspartate transaminase and alanine transaminase may also be elevated, but not exceeding 2 to 3 times the normal upper limit. Initially, the albumin and bilirubin levels in the blood might be normal but as the disease worsens, these levels may change. If the bilirubin level is high, it suggests the disease could be progressing quickly and the person may have complicated conditions like strictures or cirrhosis.
About one-fourth to almost all patients with this disease may also test positive for atypical perinuclear antineutrophil cytoplasmic antibodies, but the test is not specific to this disease. Around half of them may also have high levels of total immunoglobulins (IgM) in the blood. Certain other positive antibodies could hint at the involvement of an autoimmune disease. It is not uncommon to find an increase in certain classes of immunoglobulin, like IgG4.
Healthcare professionals usually resort to imaging techniques like ultrasound or computed tomography when liver test results persistently show a cholestatic pattern, to determine if there is any blockage in the bile duct. The diagnosis of this disease becomes likely if imaging highlights multiple narrow and dilated areas within the bile ducts in the liver or outside it.
Commonly, a technique called magnetic resonance cholangiopancreatography (MRCP) is used for acquiring a cholangiogram which is a sort of map of the bile ducts. It’s preferred since it is noninvasive and as reliable as a comparable technique called endoscopic retrograde cholangiopancreatography (ERCP), which is invasive. Percutaneous transhepatic cholangiography (PTC) is another option, reserved for patients unable to undergo MRCP or ERCP.
Usually, a liver biopsy is not needed for diagnosis unless overlapping with autoimmune hepatitis or a subset of this disease is suspected. Emerging non-invasive tools that assess the extent of fibrosis or scarring within the liver show promise. However, it’s still unclear how useful these tools are specifically for patients with this disease.
The diagnosis of this disease requires a few criteria. These include a consistently high serum alkaline phosphatase level for over six months, findings of strictures in the bile ducts using imaging methods, and ruling out the chances of secondary sclerosing cholangitis, another related condition. The hallmark feature seen under the microscope during examination of tissue biopsy, if performed, is a type of fibrosis around the bile ducts, often referred to as ‘onion-skin’ fibrosis.
Treatment Options for Primary Sclerosing Cholangitis
Treating primary sclerosing cholangitis, a disease that affects the liver’s bile ducts, is complex and can be a challenge. As of now, we don’t have a standard treatment.
One medicine that has been studied for PSC is Ursodeoxycholic acid (UDCA). However, there are mixed opinions about its use. While some European health organizations approve of using moderate doses, American health organizations do not recommend it. Despite this, it’s still used quite commonly. Several studies suggest that UDCA can improve symptoms and even survival rates of PSC patients.
Many other treatments have been tried, but none of them have been proven to work. These include a variety of drugs such as prednisolone, budesonide, colchicine and others.
For some PSC patients who have narrow bile ducts and symptoms like itching or bile duct infection, a procedure called ERCP with balloon dilatation is recommended. This can help to relieve their symptoms.
There are also surgical treatments available. These mostly involve procedures that connect the common bile duct to different parts of the digestive tract, like the duodenum or the jejunum. However, the ultimate treatment involves a liver transplant. This is usually recommended for patients with severe liver disease. This operative procedure shows promising results with a survival rate of up to 80% in five years for PSC patients.
There are also general measures that can help patients with PSC. For moderate itching, medicine like cholestyramine can help. If this doesn’t work or isn’t tolerated well, other drugs like rifampin and naltrexone can be tried.
Patients with PSC should also have their bone density checked when they’re diagnosed, and every 2 to 4 years afterwards. Additionally, people with advanced liver disease often lack certain vital nutrients, so it’s important to check for and monitor these deficiencies.
What else can Primary Sclerosing Cholangitis be?
During a diagnosis, doctors may consider various possible conditions connected with primary sclerosing cholangitis (PSC). Some of these include:
- Secondary sclerosing cholangitis, resulting from long-term bacterial infections, bile duct cancer, gallstones, repeated pancreatitis, or injury from bile duct surgery.
- IgG4-associated cholangitis, a condition related to an immune system protein.
- The overlap of PSC with autoimmune hepatitis, which is frequently found in children and young adults.
- Histiocytosis X, a rare disorder that can affect various organs.
- HIV syndrome, a stage of HIV infection.
- Bile duct strictures, where the ducts that carry bile from the liver to the gallbladder become narrow.
- Primary biliary cirrhosis, a chronic disease that slowly destroys the bile ducts in the liver.
- Papillary tumors, a form of growth that can occur in multiple organs.
All of these conditions need to be meticulously assessed to ensure a correct diagnosis.
What to expect with Primary Sclerosing Cholangitis
The course of primary sclerosing cholangitis, a liver condition, varies greatly and is hard to predict. However, if a patient has a consistently low level of alkaline phosphatase in their blood (less than 1.5 times the upper normal limit), this typically suggests a good outlook. Those with a version of the condition that affects small bile ducts also usually have a positive prognosis, with no recorded cases of bile duct cancer and very few instances of serious liver disease.
The Mayo risk score is a useful tool for predicting survival rates in those with PSC. This score takes into account factors such as age, the amounts of certain substances in the blood (bilirubin, albumin, and AST), and a history of variceal bleeding (bleeding from enlarged veins in the esophagus).
Possible Complications When Diagnosed with Primary Sclerosing Cholangitis
Primary sclerosing cholangitis is a disease that can lead to many significant complications, including:
- Deficiencies in vitamins A, D, E, and K, which are necessary for your body
- Metabolic bone disease (or osteoporosis), which weakens the bones
- Cholangiocarcinoma, a type of liver cancer
- Gallbladder cancer
- Dominant biliary strictures, a narrowing of the bile duct
- Cholangitis, an inflammation of the bile duct
- Hepatocellular carcinoma in patients with cirrhosis. This is another form of liver cancer that can develop in patients with liver fibrosis, a condition where the liver tissue becomes thick and scarred
- Colon cancer in patients with simultaneous ulcerative colitis. These patients should have their colon checked every year with a colonoscopy
- Cholelithiasis, or the formation of gallstones
- Portal hypertension, a condition where blood pressure is high in the portal vein, which carries blood to the liver
Recovery from Primary Sclerosing Cholangitis
People suffering from steatorrhea, or excess fat in their stools, should include medium-chain triglycerides in their diet. Some individuals might also need supplements that contain pancreatic enzymes. Engaging in physical activity is encouraged, but care must be taken for those with osteoporosis due to the higher risk of bone fractures.
Over the long term, these patients should have a colonoscopy. This is a procedure that checks for conditions like inflammatory bowel disease. It’s also important to monitor levels of a substance called CA 19.9 in the blood. This can provide early detection for a type of cancer known as cholangiocarcinoma.
Preventing Primary Sclerosing Cholangitis
As of now, there isn’t a guaranteed cure for primary sclerosing cholangitis, a disease that can cause liver failure. However, medical science has made important strides in diagnosing this condition earlier. Early diagnosis is crucial because it allows doctors to start treatment before the liver failure stage, potentially slowing down the progression of the condition.
