New clinical practice guidelines for primary biliary cholangitis (PBC) have been released by the European Association for the Study of the Liver (EASL) and published in the Journal of Hepatology.
The guidelines summarize the evidence of the importance of a structured, lifelong, and individualized approach for clinicians to manage patients with PBC.
“PBC is a common cause of chronic cholestasis, most notably in women over the age of 40,” stated the guidelines authors. “Disease progression results in end-stage liver disease, and many pre-treatment and on-treatment stratifiers of risk have been identified…. As a symptomatic disease, patients with PBC need attention in an ongoing manner, not only for the prevention of end-stage liver disease, but also for co-existent symptoms such as pruritus, sicca complex, and fatigue.”
The EASL has issued the following recommendations, with grade of evidence and grade of recommendation following each one in parentheses. The evidence and recommendations have been graded according to the grading of recommendations assessment development and evaluation (GRADE system).
1. Take a detailed history and administer a physical examination when evaluating patients with biochemical tests that suggest cholestatic liver disease (III, 1).
2. Ultrasound is recommended as the first-line non-invasive imaging procedure to differentiate intra- from extrahepatic cholestasis (III, 1).
3. Performing serologic screening is recommended for antimitochondrial antibodies (AMA) and PBC-specific antinuclear antibody (ANA) by immunofluorescence in all patients with unexplained cholestasis (III, 1).
4. Imaging by magnetic resonance cholangiopancreatography (MRCP) is recommended in patients with unexplained cholestasis. Endoscopic ultrasound can be an alternative to MRCP for evaluation of distal biliary disease (III, 1).
5. Consider liver biopsy after serologic screening and extended imaging in patients with ongoing unexplained intrahepatic cholestasis (III, 1).
6. Consider genetic tests for inherited cholestatic syndromes in patients when clinically appropriate (III, 1).
7. In adult patients with cholestasis and no likelihood of systemic disease, a diagnosis of PBC can be made based on elevated alkaline phosphatase (ALP) and the presence of AMA at a titre >1:40 (III, 1).
8. In the correct context, a diagnosis of AMA-negative PBC can be made in patients with cholestasis and specific ANA immunofluorescence (nuclear dots or perinuclear rims) or ELISA results (sp100, gp210) (III, 1).
9. Liver biopsy is not recommended for the diagnosis of PBC, unless PBC-specific antibodies are absent, co-existent autoimmune hepatitis (AIH) or non-alcoholic steatohepatitis (NASH) is suspected, or other (usually systemic) comorbidities are present (III, 1).
10. AMA reactivity alone is not sufficient to diagnose PBC. Follow up with patients who have normal serum liver tests who are AMA-positive with annual biochemical reassessment for the presence of liver disease (III, 1).
11. Therapy in PBC should aim to prevent end-stage complications of liver disease and manage associated symptoms. (III, 1).
12. Evaluate all patients for their risk of developing progressive PBC (III, 1).
13. Recognize that patients at greatest risk of complications from PBC are those with inadequate biochemical response to therapy and cirrhosis (II-2, 1).
14. Actively recognize that the strongest risk factors for inadequate biochemical response to therapy are early age at diagnosis (eg <45) and advanced stage at presentation (III, 1).
15. Evaluate all patients for their stage of disease using a combination of non-invasive tests (bilirubin, alkaline phosphatase, aspartate aminotransferase, albumin, platelet count, and elastography) at baseline, and during follow-up (III, 1).
16. Elevated serum bilirubin and ALP can be used as surrogate markers of outcome for patients with PBC, and routine biochemistry and hematology indices should underpin the clinical approaches to stratify individual risk of disease progression (II-2, 1).
17. Recognize that the transplant-free survival for early-stage patients with ALP <1.5× the upper limit of normal (ULN) and a normal bilirubin after 1 year of therapy with ursodeoxycholic acid (UDCA) is not significantly different to a control healthy population (II-2, 1).
18. Use elastography and risk scores (such as the GLOBE and UK-PBC score) for patients with PBC to help better define the individual risk of development of complications of advanced liver disease in the future (III, 1).
19. Oral UDCA at 13 to 15 mg/kg/day is recommended as the first-line pharmacotherapy for all patients with PBC. UDCA is usually continued for life (I, 1).
20. In a phase III study, evidence of biochemical efficacy of oral OCA has been demonstrated in patients with ALP >1.67× ULN and/or bilirubin elevated <2× ULN. Oral OCA has been conditionally approved for patients with PBC in combination with UDCA for those with an inadequate response to UDCA, or as monotherapy in those intolerant to UDCA. EASL suggests considering its use in such patients (initial dose 5 mg; dose titration to 10 mg according to tolerability at 6 months) (I, 2).