Diagnostic and Treatment Approaches for Primary Biliary Cholangitis (PBC) and Primary Sclerosing Cholangitis (PSC)
The diagnosis of PBC and PSC relies on cholestatic liver biochemistry with typical clinical and imaging features, with MRCP being the preferred imaging modality for PSC diagnosis, while treatment differs significantly: PBC responds well to ursodeoxycholic acid (UDCA) and obeticholic acid, whereas PSC has no approved medical therapy and may ultimately require liver transplantation.
Diagnostic Approach
Primary Sclerosing Cholangitis (PSC)
- Diagnosis is based on cholestatic liver biochemistry (elevated alkaline phosphatase and GGT) with typical cholangiographic features in the absence of other identifiable causes of secondary sclerosing cholangitis 1
- MRCP should be the principal imaging modality for investigation of suspected PSC with sensitivity and specificity of 80-100% and 89-100%, respectively 1, 2
- ERCP should be reserved for patients requiring tissue acquisition (e.g., cytological brushings) or therapeutic intervention 1, 2
- Liver biopsy is not routinely required but should be considered for suspected small duct PSC, assessment of overlap syndromes, or when diagnosis remains unclear 1
- Complete autoimmune serologies, including ANA, SMA, and IgG4 levels should be performed to exclude other conditions 1, 2
Primary Biliary Cholangitis (PBC)
- Diagnosis typically relies on cholestatic liver biochemistry, positive antimitochondrial antibodies (AMA), and compatible liver histology when performed 3
- Liver biopsy is not mandatory for diagnosis when clinical, biochemical, and serological data are compatible with PBC 3
- Exclusion of other causes of cholestasis is essential before confirming diagnosis 3
Treatment Approaches
Primary Sclerosing Cholangitis (PSC)
- Ursodeoxycholic acid (UDCA) is not recommended for routine treatment of classic PSC 1
- UDCA is not effective for prevention of colorectal cancer or cholangiocarcinoma in PSC patients 1
- Corticosteroids and immunosuppressants are not indicated for classic PSC 1
- In patients with PSC-AIH overlap or IgG4-related sclerosing cholangitis, corticosteroids may be beneficial 1, 3
- For symptomatic management:
Primary Biliary Cholangitis (PBC)
- UDCA at 13-15 mg/kg/day is recommended as first-line therapy for all patients with PBC 3
- Obeticholic acid is indicated for PBC patients without cirrhosis or with compensated cirrhosis without portal hypertension who have inadequate response to UDCA or are intolerant to UDCA 5
- Biochemical response to UDCA should be assessed after 1 year of therapy to identify patients at risk of progressive disease 3
- Obeticholic acid is contraindicated in PBC patients with decompensated cirrhosis, prior decompensation, or compensated cirrhosis with evidence of portal hypertension 5
Management of Complications
Primary Sclerosing Cholangitis (PSC)
- All patients with PSC should undergo colonoscopy with biopsies to screen for inflammatory bowel disease (IBD) 1
- Patients with PSC and IBD should have annual surveillance colonoscopy from the time of colitis diagnosis 4, 3
- Patients without IBD should have colonoscopy every 5 years or when symptoms develop 4
- Annual ultrasound of the gallbladder is recommended for surveillance of gallbladder polyps or malignancy 4, 2
- Cholecystectomy is recommended for gallbladder polyps ≥8 mm or smaller polyps that are growing 1
- Endoscopic screening for esophageal varices should follow international guidelines when there is evidence of cirrhosis and/or portal hypertension 1
- For dominant strictures:
Primary Biliary Cholangitis (PBC)
- All patients should be evaluated for symptoms, particularly fatigue and pruritus 3
- Risk assessment for osteoporosis should be performed in all patients 3
- Monitor for biochemical response to therapy and disease progression 5
Liver Transplantation Considerations
Primary Sclerosing Cholangitis (PSC)
- PSC is a well-recognized indication for liver transplantation 1
- Indications include:
Primary Biliary Cholangitis (PBC)
- Consider liver transplantation for patients with advanced liver disease or evidence of decompensation 3
- Patients with bilirubin levels indicating advanced liver disease should be discussed with a transplant center 3
Monitoring and Follow-up
- All patients with PSC and PBC should have risk assessment for osteoporosis 1, 4, 3
- Given the unpredictable disease course and serious nature of complications, patients should receive lifelong follow-up 1
- Non-invasive investigations should be performed in PSC patients with new/changing symptoms or evolving laboratory abnormalities 1, 3
Common Pitfalls and Caveats
- MRCP may be less sensitive than ERCP in detecting early changes of PSC and has less specificity in patients with cirrhosis 1, 2
- Cholangiography alone is insufficient to distinguish between IgG4-SC, PSC, and cholangiocarcinoma 2
- Patients with PSC have significantly increased risk of cholangiocarcinoma, which should be suspected with worsening cholestasis, weight loss, elevated tumor markers, and/or new or progressive dominant stricture 2
- Obeticholic acid can cause hepatic decompensation and failure in PBC patients with cirrhosis and must be used with caution 5
- Overlap syndromes between PBC and PSC are rare but should be considered when features of both diseases are present 1, 6