Primary Biliary Cholangitis vs Primary Sclerosing Cholangitis: Treatment Recommendations
For Primary Biliary Cholangitis (PBC), ursodeoxycholic acid (UDCA) at 13-15 mg/kg/day is mandatory first-line therapy and should be continued lifelong, whereas for Primary Sclerosing Cholangitis (PSC), UDCA is not recommended for routine treatment. 1, 2
Primary Biliary Cholangitis (PBC) Treatment
First-Line Therapy
- UDCA at 13-15 mg/kg/day (or 10-15 mg/kg/day in two divided doses) is the cornerstone of PBC treatment and must be initiated in all patients. 1, 2
- UDCA improves liver biochemistry, delays progression to liver failure, prolongs transplant-free survival, and reduces long-term risk of graft loss and liver-related death. 2, 3
- Continue UDCA lifelong, including during pregnancy and breastfeeding, as it is safe in both settings. 2
Response Assessment and Second-Line Options
- Assess biochemical response after 1 year of UDCA therapy using individualized risk stratification indices to identify patients at risk of progressive disease. 1
- For UDCA non-responders or incomplete responders, obeticholic acid (in combination with UDCA) is the established second-line therapy. 2, 3
- Fibrates (bezafibrate or fenofibrate) represent alternative second-line options, though they may be used after the first trimester in pregnancy only if benefits outweigh risks. 2, 3
- Obeticholic acid must be discontinued immediately upon pregnancy confirmation and should not be restarted during breastfeeding due to lack of safety data. 2
Post-Transplant Management
- UDCA should be given lifelong after liver transplantation to all PBC patients to prevent disease recurrence. 2
- No specific immunosuppressive regimen (including cyclosporine over tacrolimus) should be preferentially recommended to prevent PBC recurrence, as data are insufficient. 2
Primary Sclerosing Cholangitis (PSC) Treatment
Medical Management
- UDCA is NOT recommended for routine treatment of PSC. 2, 4, 1
- This strong recommendation against UDCA use is based on moderate to high-quality evidence showing lack of efficacy at standard doses and potential harm at high doses. 2
- UDCA is also NOT recommended for prevention of colorectal cancer or cholangiocarcinoma in PSC patients. 2
Immunosuppression
- Corticosteroids and immunosuppressants are NOT indicated for classic PSC. 2, 4, 1
- However, corticosteroids may be indicated in patients with PSC-autoimmune hepatitis (AIH) overlap syndrome or IgG4-related sclerosing cholangitis. 2, 4, 1
Endoscopic Management of Dominant Strictures
- ERCP should only be performed after expert multidisciplinary assessment to justify endoscopic intervention. 2, 4
- When performing ERCP for dominant strictures, pathological sampling (cytological brushings) of suspicious strictures is mandatory to exclude cholangiocarcinoma. 2, 4
- Biliary balloon dilatation is preferred over biliary stent insertion for dominant strictures. 2, 4
- Prophylactic antibiotics must be administered to all PSC patients undergoing ERCP. 2
Post-Transplant Management
- No specific immunosuppressive regimen or medical treatment is effective in preventing PSC recurrence after liver transplantation. 2
Symptom Management (Both Conditions)
Pruritus Treatment
- For PBC and PSC patients with pruritus, cholestyramine (4-8 g/day) or colestipol (5-10 g/day) is first-line treatment, given at least 4 hours after UDCA. 2, 4
- Rifampicin (300-600 mg daily) is second-line therapy for refractory pruritus. 2, 4
- Naltrexone represents an additional second-line option. 4
Nutritional Support
- Vitamin K deficiency related to cholestasis and/or use of anion exchange resins or rifampicin must be corrected. 2
- Maintain a low threshold for empirical replacement of fat-soluble vitamins (A, D, E, K) in advanced disease. 4
Surveillance and Monitoring
Gastrointestinal Surveillance
- All PSC patients must undergo colonoscopy with colonic biopsies to identify inflammatory bowel disease (IBD). 2, 4
- PSC patients with coexisting colonic IBD require annual colonoscopic surveillance from the time of colitis diagnosis due to increased colorectal cancer risk. 4
- PSC patients without IBD may benefit from colonoscopy every 5 years or earlier if new symptoms develop. 4
- Annual gallbladder ultrasound should be performed in PSC patients. 4
Portal Hypertension Screening
- Endoscopic screening for esophageal varices should follow international guidelines when cirrhosis and/or portal hypertension is evident in both PBC and PSC. 2, 1
Bone Health
- All patients with PBC and PSC require risk assessment for osteoporosis. 4, 1
- Once osteoporosis is detected, treatment and follow-up should align with national guidelines. 4
Imaging for Disease Progression
- MRCP is the principal imaging modality for suspected PSC and should be used for surveillance. 2, 4
- Non-invasive investigations (MRCP, dynamic liver MRI, contrast CT) should be performed in PSC patients with new/changing symptoms or evolving laboratory abnormalities. 2, 4
Liver Transplantation Considerations
- Both PBC and PSC are well-recognized indications for liver transplantation. 4, 1
- Eligibility and referral should be assessed according to national guidelines. 4, 1
- Patients with bilirubin levels indicating advanced liver disease or evidence of decompensation should be discussed with a transplant center. 1
Critical Pitfalls to Avoid
- Do not use UDCA routinely in PSC—this is a common error based on its success in PBC. 2
- Do not delay ERCP assessment when PSC patients develop new symptoms or worsening cholestasis, as this may indicate dominant strictures or cholangiocarcinoma. 2, 4
- Do not overlook IBD screening in PSC patients—the association is strong and impacts cancer surveillance. 2, 4
- Do not continue obeticholic acid in pregnant PBC patients—switch to UDCA monotherapy. 2