Primary sclerosing cholangitis (PSC) is a condition characterized by progressive fibrosis and strictures of both intrahepatic and extrahepatic bile ducts. The disease can also involve the pancreatic ducts, though the gallbladder is typically not affected. Its primary manifestation is intrahepatic cholestasis. The exact cause of PSC remains unclear, but it is believed to be associated with factors such as infections, genetic predisposition, and autoimmune mechanisms. Approximately 60–72% of patients with PSC also have ulcerative colitis. In these cases, inflammation of the colon can disrupt the mucosal barrier, allowing Escherichia coli from the colon to enter the bile ducts via the portal vein, leading to infection. Elevated levels of human leukocyte antigen (HLA) haplotypes B8/DR3 in affected individuals suggest an autoimmune component. Recently, PSC has been observed following hepatic arterial infusion chemotherapy. Additionally, PSC is associated with other conditions such as chronic pancreatitis, retroperitoneal fibrosis, Crohn’s disease, and rheumatoid arthritis.
Clinical Manifestations
About 70% of PSC patients are male, and the onset of the disease is usually slow. Symptoms generally appear after the age of 50, though the asymptomatic phase can last for over 10 years. The clinical presentation is non-specific, with the main symptoms being unexplained jaundice, which worsens intermittently, and dull pain in the right upper quadrant of the abdomen, often accompanied by pruritus. Some patients report fatigue, loss of appetite, weight loss, and occasionally nausea and vomiting. During episodes of cholangitis, fever may occur. As the disease progresses, patients may develop persistent obstructive jaundice, biliary cirrhosis, portal hypertension, upper gastrointestinal bleeding, or even liver failure.
Diagnosis
Diagnosing PSC in its early stages is challenging. Laboratory tests typically show elevated levels of total bilirubin, conjugated bilirubin, and alkaline phosphatase (ALP), with mild elevation of alanine aminotransferase (ALT). Imaging studies, particularly endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC), are crucial for diagnosis. Magnetic resonance cholangiopancreatography (MRCP) with clear visualization can also aid in diagnosis. Imaging typically reveals diffuse or localized strictures of the bile ducts, with the bifurcation of the hepatic ducts being prominently affected. Other findings include reduced and rigid bile duct branches or segmental strictures.
Differential Diagnosis
Secondary Sclerosing Cholangitis
This type often has identifiable causative factors for cholangitis, such as bile duct stones. It usually involves localized biliary strictures distributed according to hepatic segments or lobes, accompanied by proximal bile duct dilation. Ultrasound scans can identify bile duct stones.
Cholangiocarcinoma
Differentiating PSC from bile duct cancer using imaging can sometimes be challenging. Among patients undergoing liver transplantation for PSC, 23% have been found to have previously undiagnosed cholangiocarcinoma. Some researchers have suggested that PSC may represent a precancerous condition for bile duct cancer.
Treatment
Currently, no ideal treatment exists for PSC. Both medical and surgical approaches focus on alleviating symptoms.
Medication
Moderate doses of ursodeoxycholic acid (UDCA) [17–23 mg/(kg·d)] can improve symptoms and liver function. However, high doses of UDCA [above 28 mg/(kg·d)] have not been shown to provide clinical benefit and may increase the risk of adverse events, including a higher incidence of variceal bleeding, increased liver transplantation rates, and poorer clinical outcomes. High-dose UDCA is therefore not recommended. Other drugs, including azathioprine, methotrexate, prednisone, and cyclosporine, have been evaluated in clinical trials and found to lack significant therapeutic efficacy or the ability to improve liver biochemistry; their use is no longer recommended.
Biliary Drainage
For localized lesions, drainage can be achieved via endoscopic nasobiliary drainage (ENBD) or percutaneous transhepatic biliary drainage (PTCD), using stent placement or catheterization within the bile duct. Surgical placement of U-tube drainage may also be employed to alleviate jaundice.
Biliary-Enteric Anastomosis
For diffuse strictures, surgical intervention may involve the opening of the left and right hepatic ducts, followed by biliary-enteric anastomosis, with stent placement at the anastomotic site to facilitate drainage.
Liver Transplantation
Liver transplantation is an option for patients with cirrhosis or those whose conditions cannot be differentiated from diffuse cholangiocarcinoma. Post-transplantation outcomes are favorable, with a five-year survival rate of up to 85%.