Acute Sclerosing Cholangitis - Pathology, Causes, Diagnosis, and Treatment

What Is Acute Sclerosing Cholangitis?

Acute or primary sclerosing cholangitis causes inflammation of the bile ducts. Bile ducts help transport bile from the liver to the gallbladder. Inflammation and scarring of the bile ducts occur, blocking and narrowing the bile ducts. Blockage of the bile duct results in the accumulation of bile within the liver resulting in liver damage.

What Is the Pathology of Acute Sclerosing Cholangitis?

• The etiology and pathology of acute sclerosing cholangitis are not fully understood. Researchers believe that acute or primary sclerosing cholangitis develops in a genetically susceptible person upon exposure to some stimulus or trigger like other autoimmune disorders. The occurrence of acute sclerosing cholangitis is attributed to an immune-mediated response and is not fully an autoimmune disease. It lacks features of classic autoimmune disease: female susceptibility, response to immunosuppressants, and autoantibodies. HLA alleles A1, B8, and DR3 are the most common genes in primary acute sclerosing cholangitis.

• Acute sclerosing cholangitis is closely associated with inflammatory bowel disease. Researchers have developed a leaky gut hypothesis, which suggests the association of inflammatory bowel disease with acute sclerosing cholangitis.

• The intestinal flora migrates from the infected gastrointestinal tract to the portal venous system resulting in an inflammatory response that disrupts the biliary epithelial cells. As a result, the bile acids act on cholangiocytes (epithelial cells of the bile duct that secret and modify bile) and cause injury and inflammation of the bile duct. Immune response to an antigen causes inflammation of the bile duct and intestine.

• Myofibroblasts are activated due to cytokines, tumor necrosis factor, interleukin, transforming growth factor, CD4, and CD8 cells cause and result in an inflammatory response and tissue fibrosis.

• Epithelium of the bile duct system also releases ligands and intracellular and vascular adhesion molecules. These molecules cause biliary inflammation and inflammation of the bile duct system in acute sclerosing cholangitis due to leukocytic migration.

• The T and B cells of the intestines are programmed to cause biliary inflammation upon pathogen encounter, thus explaining the interconnection between gut and liver pathology.

• Damage to the bile duct system due to ischemia (decreased blood supply within a tissue) also results in inflammation and scarring of the bile ducts. Therefore, it is considered one of the factors for the development of acute sclerosing cholangitis. It is presumed that genetic factors and external antigen exposure due to which immune response develops in a person are the main causes of acute or primary sclerosing cholangitis.

What Are the Causes of Acute Sclerosing Cholangitis?

Although the exact cause of the disease is unknown, it is believed that many factors are responsible for acute sclerosing cholangitis:

• Genetic.

• Problems with the immune system.

• Injury to the bile duct system due to bile acid action.

• Changes in the intestinal bacterial flora.

What Are the Symptoms of Acute Sclerosing Cholangitis?

The initial symptoms of acute sclerosing cholangitis include abdominal pain, itching of the skin, loose motion or diarrhea, fever, weakness, and jaundice, due to which the skin color changes to yellow. As the disease progresses, bile duct infection is noted due to obstruction of the bile duct. The symptoms include pain on the right side of the upper abdomen, fever, and severe jaundice. During the late stages, cirrhosis is seen in the patients. The symptoms include bleeding due to swollen veins and swelling due to fluid accumulation, known as ascites. Hepatic encephalopathy results from toxin accumulation in the brain due to liver damage. Jaundice and edema are also seen.

What Are the Diagnostic Tests Performed in Acute Sclerosing Cholangitis?

• Liver Function Test- Serum bilirubin, serum alkaline phosphatase, and serum aminotransferase are elevated. Hypergammaglobulinemia is also noted in many patients.

• Imaging Tests:

  • Magnetic Resonance Cholangiopancreatography - This helps assess the constriction or dilatation of the bile ducts both outside and inside the liver. It is usually done with magnetic resonance imaging (MRI) to assess liver and biliary lesions.

  • Endoscopic Retrograde Cholangiopancreatography - It is mainly used for treatment rather than diagnostic purposes.

  • Ultrasonography - Ultrasound of the gallbladder and liver is performed during initial investigations.

What Is the Treatment of Acute Sclerosing Cholangitis?

A proper therapy for acute sclerosing cholangitis is not available. Medicines are given to the patients to treat symptoms and complications present in them. The treatment method also depends on the severity and disease progression. Gastroenterologist is the doctor who is in charge of the patient. Liver transplantation is the only specific treatment that can be advocated in acute sclerosing cholangitis cases.

• Medicines - They have not shown any important changes in the disease progression and disease process. The medicines provided to the patients are immunosuppressants, bile salts, chelators, and steroids.

• Treatment for Blocked Bile Ducts - Endoscopic retrograde cholangiopancreatography (ERCP) is done by doctors to treat narrow and blocked bile ducts. Stents (tiny tubes) are used to keep the bile ducts open.

• Liver Transplant - A liver transplant is indicated whenever there is variceal bleeding (bleeding through the varices that are abnormal and dilated veins), ascites, recurrent episodes of inflammation of the bile duct, hepatic encephalopathy (loss of brain activities due to liver damage), and liver failure.

• Diet Modification - Consumption of medium-chain triglycerides, like coconut and palm oil, is advised for patients with steatorrhoea (excretion of fats in the feces). Supplements for fat-soluble vitamins are needed. Few patients may require calcium supplementation due to the presence of bone disease.

• Lifestyle Modification - Physical activities are modified or restricted; however, in patients with bone disease, physical activities should be modified as per the patient’s need.

• Consultations - A gastroenterologist treats and performs surgery for a liver transplant on the patient. In the presence of bone disease, an endocrinologist is consulted.

• Long-Term Monitoring - Most acute or primary sclerosing cholangitis deaths result from cancer. Hence, all the patients presented with primary sclerosing cholangitis should undergo screening and monitoring regularly for cancer. A colonoscopy or biopsy should be done to eliminate inflammatory bowel disease. Colonoscopy should be conducted yearly on these patients to eliminate the possibility of colorectal cancer. Ultrasound of the gallbladder is done yearly to check for gallbladder cancer.

Conclusion:

Acute sclerosing cholangitis is a chronic liver condition characterized by bile duct inflammation and fibrosis and thus resulting in decreased bile flow from the liver to the gallbladder. Very little information is available on the pathology and etiology of the disease; however, the autoimmune condition is considered the leading cause. Liver transplantation is needed in patients due to liver damage and, eventually, cirrhosis of the liver and liver cancer.