Last updated March 15, 2022

Primary Biliary Cholangitis

Guidance Statements

Diagnosis

1. The diagnosis of PBC can be established when two of the following three criteria are met:
  • 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
2. The diagnosis of AMA-negative PBC does not require a liver biopsy if other criteria are met, including cholestatic liver tests and PBC-specific autoantibodies such as sp100 or gp210.

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.

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.
 

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.
 

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.

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.

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

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.

 

Recommendation Grading

Overview

Title

Primary Biliary Cholangitis

Authoring Organization

Publication Month/Year

August 24, 2021

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.