Primary Biliary Cholangitis
Publication Date: August 24, 2021
Last Updated: March 14, 2022
Guidance Statements
Diagnosis
1. The diagnosis of PBC can be established when two of the following three criteria are met:
3. Liver biopsy to rule out concomitant AIH or other liver disease should be considered in PBC patients when the alanine aminotransferase activity is more than 5 times the upper limit of normal.
4. In cases of suspected PBC/AIH overlap, treatment should be targeted at the predominant histological pattern of injury.
- Biochemical evidence of cholestasis based on ALP elevation.
- Presence of AMA, or other PBC-specific autoantibodies, including sp100 or gp210, if AMA is negative.
- Histologic evidence of nonsuppurative destructive cholangitis and destruction of interlobular bile ducts
3. Liver biopsy to rule out concomitant AIH or other liver disease should be considered in PBC patients when the alanine aminotransferase activity is more than 5 times the upper limit of normal.
4. In cases of suspected PBC/AIH overlap, treatment should be targeted at the predominant histological pattern of injury.
Therapy
5. UDCA in a dose of 13 to 15 mg/kg/day orally is recommended for patients with PBC who have abnormal liver enzyme values regardless of histologic stage.
6. For patients requiring bile acid sequestrants, UDCA should be given at least 1 hour before or 4 hours after the bile acid sequestrant.
7. Biochemical response to UDCA should be evaluated at 12 months after treatment initiation to determine whether patients should be considered for second-line therapy.
8. Patients who are inadequate responders to UDCA (Table 1) should be considered for treatment with OCA, starting at 5 mg/day.
9. Fibrates can be considered as off-label alternatives for patients with PBC and inadequate response to ursodeoxycholic acid, although fibrates are discouraged in patients with decompensated liver disease.
10. OCA is contraindicated in patients with advanced cirrhosis. This is defined as cirrhosis with current or prior evidence of liver decompensation (e.g., encephalopathy, coagulopathy) or portal hypertension (e.g., ascites, gastroesophageal varices, or persistent thrombocytopenia). Furthermore, we would recommend careful monitoring of any patient with cirrhosis, even if not advanced, receiving OCA.
6. For patients requiring bile acid sequestrants, UDCA should be given at least 1 hour before or 4 hours after the bile acid sequestrant.
7. Biochemical response to UDCA should be evaluated at 12 months after treatment initiation to determine whether patients should be considered for second-line therapy.
8. Patients who are inadequate responders to UDCA (Table 1) should be considered for treatment with OCA, starting at 5 mg/day.
9. Fibrates can be considered as off-label alternatives for patients with PBC and inadequate response to ursodeoxycholic acid, although fibrates are discouraged in patients with decompensated liver disease.
10. OCA is contraindicated in patients with advanced cirrhosis. This is defined as cirrhosis with current or prior evidence of liver decompensation (e.g., encephalopathy, coagulopathy) or portal hypertension (e.g., ascites, gastroesophageal varices, or persistent thrombocytopenia). Furthermore, we would recommend careful monitoring of any patient with cirrhosis, even if not advanced, receiving OCA.
Management of Symptoms
Pruritis
11. Anion-exchange resins should be used as initial therapy for patients with PBC who have pruritus.
12. The following agents can be used for pruritus refractory to anion-exchange resins:
a. Rifampicin 150 to 300 mg twice daily.
b. Oral opiate antagonists such as naltrexone titrated to a dose of 50 mg daily.
c. Sertraline 75 to 100 mg daily.
12. The following agents can be used for pruritus refractory to anion-exchange resins:
a. Rifampicin 150 to 300 mg twice daily.
b. Oral opiate antagonists such as naltrexone titrated to a dose of 50 mg daily.
c. Sertraline 75 to 100 mg daily.
Dry Mouth
13. Management of dry eyes can include the following:
a. Artificial tears should be used initially.
b. Pilocarpine or cevimeline can be used in patients for whom symptoms are refractory to artificial tears.
c. Cyclosporine or lifitegrast ophthalmic emulsion can be used in those whose disease is refractory to other agents, preferably under the supervision of an ophthalmologist.
14. The following therapies should be used for xerostomia and dysphagia:
a. Over-the-counter saliva substitutes can be tried.
b. Pilocarpine or cevimeline can be used if patients remain symptomatic despite saliva substitutes.
a. Artificial tears should be used initially.
b. Pilocarpine or cevimeline can be used in patients for whom symptoms are refractory to artificial tears.
c. Cyclosporine or lifitegrast ophthalmic emulsion can be used in those whose disease is refractory to other agents, preferably under the supervision of an ophthalmologist.
14. The following therapies should be used for xerostomia and dysphagia:
a. Over-the-counter saliva substitutes can be tried.
b. Pilocarpine or cevimeline can be used if patients remain symptomatic despite saliva substitutes.
Management of Portal Hypertension
15.Patients with suspected cirrhosis should undergo endoscopic screening for varices at the time of diagnosis.
16.Regular screening for hepatocellular carcinoma with cross-sectional imaging at 6-month intervals is currently advised for men and patients with cirrhosis.
16.Regular screening for hepatocellular carcinoma with cross-sectional imaging at 6-month intervals is currently advised for men and patients with cirrhosis.
Osteopenia/Osteoporosis
17.Patients with PBC should be provided 1,000 to 1,500 mg of calcium and 1,000 International Units of vitamin D daily in the diet and as supplements if needed.
18.Oral alendronate (70 mg weekly) or other effective bisphosphonates should be considered if patients are osteoporotic. Oral bisphosphonates should be avoided if patients have acid reflux or known varices.
18.Oral alendronate (70 mg weekly) or other effective bisphosphonates should be considered if patients are osteoporotic. Oral bisphosphonates should be avoided if patients have acid reflux or known varices.
Hyperlipidemia
19. Patients with elevated lipid levels and at risk for cardiovascular disease can be considered for lipid-lowering therapy.
Fat-Soluble Vitamins
20. Fat-soluble vitamin deficiencies should be treated with parenteral or water-soluble supplements.
Liver Transplantation
21. Patients with manifestations of end-stage PBC should be referred for liver transplantation when their Model for End-Stage Liver Disease score exceeds 14.
Follow-Up of PBC
Having trouble viewing table?
| Liver tests every 3-6 months |
|---|
| TSH annually |
| Bone mineral densitometry every 2 years |
| Vitamins A, D, E and prothrombin time annually if bilirubin >2.0 |
| Upper endoscopy every 1-3 years if cirrhotic, Mayo risk score >4.1, or transient elastography shows a score ≥17 kPa* |
| Ultrasound with or without alpha fetoprotein in patients with known or suspected cirrhosis† and men every 6 months |
Changes from the 2018 PBC Guidelines
In May 2021, the Food and Drug Administration issued a new warning restricting the use of OCA in patients with advanced cirrhosis.[2] This is defined as cirrhosis with current or prior evidence of liver decompensation (e.g., encephalopathy, coagulopathy) or portal hypertension (e.g., ascites, gastroesophageal varices, or persistent thrombocytopenia).
Two guidance statements that were published in the 2018 practice guidance on PBC have been revised as follows:
9. Fibrates can be considered as off-label alternatives for patients with PBC and inadequate response to ursodeoxycholic acid, although fibrates are discouraged in patients with decompensated liver disease.
10. OCA is contraindicated in patients with advanced cirrhosis. This is defined as cirrhosis with current or prior evidence of liver decompensation (e.g., encephalopathy, coagulopathy) or portal hypertension (e.g., ascites, gastroesophageal varices, or persistent thrombocytopenia). Furthermore, we would recommend careful monitoring of any patient with cirrhosis, even if not advanced, receiving OCA.
Two guidance statements that were published in the 2018 practice guidance on PBC have been revised as follows:
9. Fibrates can be considered as off-label alternatives for patients with PBC and inadequate response to ursodeoxycholic acid, although fibrates are discouraged in patients with decompensated liver disease.
10. OCA is contraindicated in patients with advanced cirrhosis. This is defined as cirrhosis with current or prior evidence of liver decompensation (e.g., encephalopathy, coagulopathy) or portal hypertension (e.g., ascites, gastroesophageal varices, or persistent thrombocytopenia). Furthermore, we would recommend careful monitoring of any patient with cirrhosis, even if not advanced, receiving OCA.
Recommendation Grading
Overview
Title
Primary Biliary Cholangitis
Authoring Organization
American Association for the Study of Liver Diseases
Publication Month/Year
August 24, 2021
Last Updated Month/Year
July 14, 2023
Supplemental Implementation Tools
Document Type
Guideline
External Publication Status
Published
Country of Publication
US
Document Objectives
This guidance identifies preferred approaches to the diagnostic and therapeutic aspects of care for patients with PBC.
Target Patient Population
Patients with primary biliary cholangitis
Inclusion Criteria
Male, Female, Adolescent, Adult, Older adult
Health Care Settings
Ambulatory, Hospital, Outpatient
Intended Users
Nurse, nurse practitioner, physician, physician assistant
Scope
Diagnosis, Treatment, Management
Diseases/Conditions (MeSH)
D001652 - Bile Ducts, D001327 - Autoimmune Diseases, D002761 - Cholangitis, D001649 - Bile Duct Diseases
Keywords
autoimmune disease, cholangitis, bile ducts
Source Citation
Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M. Primary biliary cholangitis: 2021 practice guidance update from the American Association for the Study of Liver Diseases. Hepatology. 2021 Aug 24. doi: 10.1002/hep.32117. Epub ahead of print. PMID: 34431119.