Primary Sclerosing Cholangitis (PSC)
By David Assis, MD
Primary Sclerosing Cholangitis (PSC) is a rare, chronic disease of the bile ducts with an unknown cause that results in scars and inflammation of the biliary system. Patients with PSC may develop severe liver problems including cirrhosis, cancer and the need for a liver transplant. Despite decades of searching, there is no known cure or treatment that can slow the progression of PSC. Therefore, breakthroughs in research and clinical practice are urgently needed and greater partnership between medical providers and patients can help accomplish this important goal.
The biliary system allows the body to process and eliminate bile, which is made in the liver. Bile itself is a mechanism to dispose of waste products from liver metabolism, and also helps with digestion in the GI tract. If bile cannot be eliminated from the liver, due to scars and blockages of the bile ducts, liver inflammation results and over time this can lead to severe scars (known as cirrhosis). The precise cause of the bile duct problems in PSC is not known but it is thought that the immune system attacks the bile duct cells and causes injury. In addition, there is evidence that the bile itself in PSC is abnormal and more toxic, predisposing to inflammation within the liver.
The highest prevalence of PSC is found in northern Europe, where it is one of the most common causes of advanced liver disease and transplantation. PSC is also found across the world including the United States. It is thought that approximately 30,000 Americans have PSC although this number may be an underestimate many patients who live far from larger academic centers may not have their disease recognized and diagnosed.
Contrary to most other autoimmune diseases, PSC occurs more frequently in men compared to women. It can present at almost any age, ranging from teenagers to the elderly. Up to 80% of PSC patients also have inflammatory bowel disease (IBD), including Ulcerative Colitis and Crohn’s Disease. While only a small minority of IBD patients will have PSC (5%), any patient with colitis should have liver lab testing to exclude the possibility of PSC.
Some PSC patients do not have any symptoms, however many patients have symptoms caused by disruption in the bile flow, including fatigue, itching, abdominal pain, and jaundice (yellow color of the eyes/skin). If scars result in a complete blockage of a bile duct, bacteria can then enter the biliary tree and cause an infection of the biliary system called cholangitis. Over time, chronic problems with bile flow result in cirrhosis which itself can cause fluid retention, GI bleeding and end-stage liver disease.
Patients with PSC have an increased risk of cancer. The three most common ones include bile duct cancer (called cholangiocarcinoma), colon cancer, and gallbladder cancer. Although most patients with PSC will not develop these cancers, cholangiocarcinoma is one of the most common deadly complications in these patients. Finally, patients with PSC have an elevated risk of bone loss causing osteoporosis, and the milder version called osteopenia.
PSC is diagnosed by finding bile duct scars (also known as strictures), typically in large liver bile ducts and/or the ducts that takes bile from the liver to the GI tract. The scars are usually diagnosed with an imaging test such as magnetic resonance imaging (MRI). In the past, an endoscopic procedure called an endoscopic retrograde cholangiopancreatography (ERCP) was needed, however the MRI is both less invasive and as accurate as the endoscopy. A small number of patients have damage to small bile ducts that is seen only with a liver biopsy. It is important to exclude other causes of liver and bile duct problems such as infections and vascular problems.
Once PSC is diagnosed it is important to determine if the patient also has IBD. A colonoscopy should be performed if it has not already been done in the past. The patient should have liver labs tested to understand how much inflammation is present along the bile ducts and in the liver. It is also important to obtain a bone density scan to evaluate for bone health and begin calcium and vitamin D supplementation.
Monitoring PSC includes obtaining liver tests at least twice per year, imaging the liver and bile ducts once per year to screen for bile duct cancer, colonoscopy once per year (especially in patients who also have colitis) to screen for colon cancer. Several medications can reduce the urge to itch and help eliminate bile acids from the GI tract. For patients who develop an abrupt bile duct blockage leading to infection (cholangitis) and jaundice, antibiotics and an endoscopic procedure (ERCP) to relieve the blockage may be needed. Patients with advanced liver disease due to PSC may need evaluation for liver transplantation. Transplant outcomes for PSC are good and patients can receive a whole liver (cadaveric) or a partial liver (living donation). There is a risk of recurrent PSC after transplant, and monitoring of liver function and management of colitis is necessary after transplantation.
There is no effective treatment for PSC as of now. Patients may be treated with Ursodiol (or Actigall), which improves bile flow. While this medication in moderate doses is safe and improves liver lab tests, Ursodiol cannot stop the progression of PSC or improve the existing scars. At high doses, Ursodiol may result in liver complications and a discussion between the patient and provider should occur before it is started. Fortunately, there is a rapidly growing interest among researchers and pharmaceutical companies to develop new treatments for PSC by reducing inflammation, bile acid toxicity, and scars in the bile ducts, and by redirecting the immune system. There is hope that these efforts will produce one or more therapies to improve liver function.
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