Primary biliary cholangitis

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 21 Nov 2024

Last updated: 04 Dec 2024

04 Dec 2024

FDA grants approval of seladelpar, expanding options for second-line treatment

The Food and Drug Administration (FDA) has granted accelerated approval to seladelpar, a peroxisome proliferator-activated receptor (PPAR) agonist, for the treatment of primary biliary cholangitis (PBC). This is the second PPAR agonist approved by the FDA this year for PBC, after the accelerated approval of elafibranor in June. Both PPAR agonists provide additional second-line options for disease-modifying therapy in patients with PBC.

Up to 40% of patients with PBC experience inadequate response to first-line treatment with ursodiol, significantly increasing their risk of death or needing liver transplantation.[48][49] Previously, obeticholic acid was the only second-line option available.

Phase 3 trials of elafibranor and seladelpar demonstrated improved biochemical response compared with placebo.[53][54] The seladelpar trial also reported improvements in pruritus, a symptom that can significantly affect quality of life in patients with PBC and is not improved by other disease-modying therapies.[54]

Elafibranor and seladelpar are indicated for use:

in combination with ursodiol for patients with an inadequate response to ursodiol; or
as monotherapy for patients who cannot tolerate ursodiol.

They should not be used in patients who have or develop decompensated cirrhosis.

The European Medicines Agency (EMA) has granted a conditional marketing authorization to elafibranor for this indication, but seladelpar is not currently available in Europe (except as an orphan drug).

See Management: approach

Original source of update

Primary biliary cholangitis (PBC) is characterized by progressive intrahepatic bile duct damage and loss.

PBC is significantly more common in women than in men. Peak incidence is around age 40 years, and median age at diagnosis is 65 years.

The combination of a cholestatic pattern of serum liver tests (elevated alkaline phosphatase, gamma-glutamyl transferase, or both) and a PBC-specific autoantibody (typically antimitochondrial antibody) is sufficient for diagnosis in most patients, with no need for biopsy confirmation.

PBC is progressive in most patients; although, in many people, the rate of progression can be so slow that it may not be clinically relevant. Cirrhosis and its typical complications arise in the end stage.

Symptoms (typically pruritus and fatigue) can significantly lower the quality of life, even in patients with a very slowly progressive disease. These symptoms warrant treatment in their own right using specific regimens.

Progression of the disease can be slowed by therapy with ursodiol.

In patients with an inadequate response to ursodiol, second-line options include obeticholic acid, elafibranor, or seladelpar.

Transplantation is an effective treatment for patients who develop end-stage liver disease with PBC.

Definition

Primary biliary cholangitis (PBC) is a chronic disease of the small intrahepatic bile ducts that is characterized by progressive bile duct damage (and eventual loss) occurring in the context of chronic portal tract inflammation. Fibrosis develops as a consequence of the original insult and the secondary effects of toxic bile acids retained in the liver, resulting ultimately in cirrhosis. The almost universal presence of autoantibodies (classically antimitochondrial antibodies) has led to the widely held view that PBC is an autoimmune disease.[1]

History and exam

Key diagnostic factors

age 40-65 years
female sex
family history of PBC

Full details

Other diagnostic factors

personal history of autoimmune disease
family history of autoimmune disease
history of hypercholesterolemia
itch
fatigue
dry eyes and dry mouth
abdominal discomfort
sleep disturbance
hepatomegaly
xanthelasmata
postural dizziness/blackouts
memory and concentration problems
jaundice
ascites
splenomegaly
skin pigmentation

Full details

Risk factors

female sex
age between 40 and 65 years
family history of PBC
family history of autoimmune disease
smoking
urinary tract infection

Full details

Diagnostic tests

1st tests to order

alkaline phosphatase (ALP)
gamma-glutamyl transferase (GTT)
bilirubin
alanine aminotransferase (ALT)
serum albumin
antimitochondrial antibody (AMA) immunofluorescence
antinuclear antibody (ANA) immunofluorescence
antipyruvate dehydrogenase complex-E2 ELISA
anti-M2 ELISA
antiglycoprotein-210 ELISA
anti-Sp100 ELISA
abdominal ultrasound scan
magnetic resonance cholangiopancreatography (MRCP)
transient elastography

Full details

Tests to consider

serum immunoglobulin
liver biopsy

Full details

Treatment algorithm

ACUTE

early-stage disease

developing end-stage liver disease or refractory pruritus

Contributors

Authors

David Bernstein, MD

Professor of Medicine

NYU Grossman School of Medicine

Director, Gastroenterology and Hepatology

Ambulatory Network-Long Island

NYU Langone Health

New York

Disclosures

DB is a consultant for Ipsen. DB is on the speakers bureau for Ipsen and Intercept.

Acknowledgements

Dr David Bernstein would like to gratefully acknowledge Dr David E. J. Jones, the previous contributor to this topic. DEJJ has received speaker honoraria from Falk, Intercept, and Abbott, grant funding from Intercept and Pfizer, and has undertaken consultancy work for Falk, GSK, Intercept, and Novartis. DEJJ is an author of a number of articles referenced in this topic.

Peer reviewers

James Neuberger, BM, BCh

Consultant Physician

Liver Unit

Queen Elizabeth Hospital

Birmingham

Disclosures

JN declares that he has no competing interests.

Ian R. Mackay, AM, MD, FAA, FRACP, FRCPA, FRCP

Department of Biochemistry and Molecular Biology

Monash University

Clayton

Victoria

Australia

Disclosures

IRM declares that he has no competing interests.

Alia S. Dadabhai, MD

Assistant Professor

Gastroenterology and Hepatology Division

Johns Hopkins University

Baltimore

Disclosures

AD declares that she has no competing interests.

Differentials
- Obstructive bile duct lesion
- Small-duct primary sclerosing cholangitis
- Drug-induced cholestasis
More Differentials
Guidelines
- AASLD practice guideline on imaging-based non-invasive liver disease assessments of hepatic fibrosis and steatosis
- EASL clinical practice guidelines on non-invasive tests for evaluation of liver disease severity and prognosis - 2021 update
More Guidelines
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Primary biliary cholangitis

FDA grants approval of seladelpar, expanding options for second-line treatment

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Tests to consider

Treatment algorithm

early-stage disease

developing end-stage liver disease or refractory pruritus

Contributors

Authors

David Bernstein, MD

Disclosures

Acknowledgements

Peer reviewers

James Neuberger, BM, BCh

Disclosures

Ian R. Mackay, AM, MD, FAA, FRACP, FRCPA, FRCP

Disclosures

Alia S. Dadabhai, MD

Disclosures

Differentials

Guidelines

Log in or subscribe to access all of BMJ Best Practice

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