Primary Sclerosing Cholangitis
Primary Sclerosing Cholangitis (PSC) is a chronic, progressive cholestatic liver disease characterized by inflammation, fibrosis, and stricturing of the intrahepatic and/or extrahepatic bile ducts, ultimately leading to biliary cirrhosis, portal hypertension, and liver failure. The pathogenesis of PSC is incompletely understood, but it is believed to involve a combination of genetic susceptibility, dysregulated immune responses, and environmental triggers. The disease is strongly associated with inflammatory bowel disease, particularly ulcerative colitis, suggesting an immunologic link. Histopathologically, PSC is marked by concentric ('onion-skin') periductal fibrosis and obliterative cholangitis. Over time, chronic biliary obstruction results in progressive liver damage, culminating in cirrhosis and its complications. PSC also significantly increases the risk of cholangiocarcinoma, gallbladder carcinoma, and colorectal cancer in patients with concomitant inflammatory bowel disease. The health impacts are profound, with most patients experiencing progressive liver dysfunction, pruritus, fatigue, and recurrent episodes of cholangitis, ultimately requiring liver transplantation in advanced cases.
This is the most common form of PSC, characterized by multifocal strictures and beading of both intrahepatic and extrahepatic bile ducts. It typically affects middle-aged men and is frequently associated with inflammatory bowel disease, particularly ulcerative colitis. The disease course is generally progressive, with many patients developing cirrhosis and its complications over time.
Small duct PSC is defined by clinical, biochemical, and histological features of PSC but with normal cholangiographic imaging of the large bile ducts. Diagnosis is established by liver biopsy demonstrating periductal fibrosis and inflammation. Small duct PSC is more common in younger patients and women, and is also associated with inflammatory bowel disease. The prognosis is generally more favorable than classic PSC, with a lower risk of progression to cirrhosis and cholangiocarcinoma.
These refer to cases where features of PSC coexist with other autoimmune liver diseases, most commonly autoimmune hepatitis. Patients may exhibit laboratory, histological, or clinical findings of both conditions. Overlap syndromes may require distinct therapeutic considerations and may influence disease progression and prognosis.
Primary Sclerosing Cholangitis is an uncommon disease with a prevalence estimated at 6–16 cases per 100,000 individuals in Western countries. The incidence is approximately 0.5–1.3 per 100,000 person-years. PSC predominantly affects men, with a male-to-female ratio of about 2:1, and is most commonly diagnosed between the ages of 30 and 50 years. Up to 80% of patients with PSC have concomitant inflammatory bowel disease, most frequently ulcerative colitis. The disease is less common in Asian and African populations. PSC is associated with a significantly increased risk of hepatobiliary malignancies, particularly cholangiocarcinoma, which develops in 7–15% of patients over their lifetime. The median survival from diagnosis to liver transplantation or death ranges from 12 to 18 years, though this varies depending on disease subtype, presence of comorbidities, and access to liver transplantation.
The diagnosis of Primary Sclerosing Cholangitis is based on a combination of clinical, biochemical, radiological, and histological findings. Patients typically present with cholestatic liver enzyme abnormalities, including elevated alkaline phosphatase and gamma-glutamyl transferase, often accompanied by mild elevations in transaminases. Magnetic resonance cholangiopancreatography (MRCP) is the imaging modality of choice, revealing multifocal strictures and segmental dilatations ('beading') of the bile ducts. Endoscopic retrograde cholangiopancreatography (ERCP) may be used for diagnostic confirmation or therapeutic intervention but is generally reserved for cases where MRCP is inconclusive or intervention is required. Liver biopsy is not routinely necessary but may be indicated in cases with normal cholangiography (suspected small duct PSC) or to evaluate for overlap syndromes or advanced fibrosis. Diagnostic criteria include chronic cholestatic liver enzyme pattern, characteristic cholangiographic findings, and exclusion of secondary causes of sclerosing cholangitis such as bile duct obstruction, ischemic injury, or infections. Additional laboratory evaluation may include autoimmune serologies, immunoglobulin levels, and screening for associated inflammatory bowel disease. Surveillance for cholangiocarcinoma and colorectal cancer is recommended due to increased risk in this population.
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