Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Feb 1;118(2):232-242.
doi: 10.14309/ajg.0000000000002070. Epub 2022 Sep 21.

Application of the Latest Advances in Evidence-Based Medicine in Primary Biliary Cholangitis

Kris V Kowdley  1 , Christopher L Bowlus  2 , Cynthia Levy  3 , Marlyn J Mayo  4 , Daniel S Pratt  5 , Raj Vuppalanchi  6 , Zobair M Younossi  7
Affiliations

Application of the Latest Advances in Evidence-Based Medicine in Primary Biliary Cholangitis

Kris V Kowdley et al. Am J Gastroenterol. .

Abstract

Primary biliary cholangitis (PBC) is a chronic, cholestatic, autoimmune liver disease that can progress to end-stage liver disease and its complications. A previous expert review panel collaborated on a consensus document for gastroenterologists and other healthcare professionals regarding the care of patients with PBC. Subsequently, there have been several recent important developments in the diagnosis, treatment, and monitoring of patients with PBC. These include updates to prognostic models on risk stratification, new noninvasive tools for staging of disease, updates to the appropriate use of and long-term treatment results with obeticholic acid as a second-line treatment, the emerging therapeutic role of fibrates, and the advancement of investigational agents for managing PBC. In this updated expert consensus document, we provide updates on staging, the use of noninvasive prognostic tools, and a treatment algorithm to provide evidence-based and practical tools for clinicians who manage PBC, with the ultimate goal to improve the long-term outcomes for patients with this chronic liver disease.

PubMed Disclaimer

Conflict of interest statement

Guarantor of the article: Kris V. Kowdley, MD.

Specific author contributions: K.V.K.: led the group of expert authors and drafted the proposed outline, identified the most recent updates in PBC data, developed the updated PBC treatment algorithm and other practical recommendations in the manuscript, drafted the manuscript on updated PBC data and the use of the new algorithm, has approved the final draft. C.L.B.: reviewed and approved the proposed outline; performed literature searches and identified the most recent updates in PBC literature, contributed to the development of the updated PBC treatment algorithm and other practical recommendations in the manuscript, drafted the manuscript on updated PBC data and the use of the new algorithm, approved the final draft. C.L.: reviewed and approved the proposed outline, performed literature searches and identified the most recent updates in PBC literature, contributed to the development of the updated PBC treatment algorithm and other practical recommendations in the manuscript, drafted the manuscript on updated PBC data and the use of the new algorithm, has approved the final draft. M.J.M.: reviewed and approved the proposed outline, performed literature searches and identified the most recent updates in PBC literature, contributed to the development of the updated PBC treatment algorithm and other practical recommendations in the manuscript, drafted the manuscript on updated PBC data and the use of the new algorithm, has approved the final draft. D.S.P.: reviewed and approved the proposed outline, performed literature searches and identified the most recent updates in PBC literature, contributed to the development of the updated PBC treatment algorithm and other practical recommendations in the manuscript, drafted the manuscript on updated PBC data and the use of the new algorithm, has approved the final draft. R.V.: reviewed and approved the proposed outline, performed literature searches and identified the most recent updates in PBC literature, contributed to the development of the updated PBC treatment algorithm and other practical recommendations in the manuscript, drafted the manuscript on updated PBC data and the use of the new algorithm, has approved the final draft. Z.M.Y.: reviewed and approved the proposed outline, performed literature searches and identified the most recent updates in PBC literature, contributed to the development of the updated PBC treatment algorithm and other practical recommendations in the manuscript, drafted the manuscript on updated PBC data and the use of the new algorithm, has approved the final draft.

Financial support: This manuscript was supported by an unrestricted educational grant to the Chronic Liver Disease Foundation from Intercept Pharmaceuticals. The selection of the authors and creation of this manuscript was performed independently. Intercept Pharmaceuticals did not play a role.

Potential competing interests: K.V.K.: advisory role: Cymabay, Genfit, HighTide, Intercept, Mirum, Gilead, Madrigal, and NGM; consultant: Calliditas; research funding: Cymabay, Genfit, Glaxo Smith Kline, HighTide, Mirum, Gilead, Pliant, Viking, Pfizer, Intercept, Hanmi, and Madrigal. C.L.B.: research funding: Gilead, BMS, Cymabay Therapeutics, Genfit, Glaxo Smith Kline, Mirum, Pliant, Novartis, BiomX, Boston Scientific, COUR Pharmaceuticals, and Target PharmaSolutions. C.L.: advisory role: Calliditas, Cara, Cymabay, Genfit, Glaxo Smith Kline, Intercept, Mirum, and Target; research funding: Calliditas, Cara, Cymabay, Genfit, Gilead Sciences, Glaxo Smith Kline, HighTide, Intercept, Mirum, Target, and Zydus. M.J.M.: advisory role: Cymabay, and Glaxo Smith Kline; research funding: Cymabay, Genfit, Glaxo Smith Kline, Mirum, Target Pharmaceuticals, and Intercept. D.S.P.: consultant: Mediar Therapeutics; research funding: Lygenesis, Cara, Gilead Sciences, Cymabay, Genfit, and HighTide. R.V.: advisory role: Echosens; consultant: Data safety monitoring boards for Labcorp, Medpace, and COUR Pharmaceuticals; research funding: Institutional funding from Zydus Therapeutics, Pliant, Eli Lilly, Galectin, Terns, and Cara Therapeutics. Z.M.Y.: consultant: Novo Nordisk, Merck, Siemens, Intercept, Gilead Sciences, Astra Zeneca, Madrigal, BMS, AbbVie, Abbott, and Novartis

Figures

Figure 1.
Figure 1.
Recommendations for staging and predicting outcomes in PBC. ALP, alkaline phosphatase; kPa, kilopascal; LSM, liver stiffness measurement; MRE, magnetic resonance imaging; PBC, primary biliary cholangitis; TE, transient elastography; ULN, upper limit of normal; VCTE, vibration-controlled transient elastography.
Figure 2.
Figure 2.
Symptoms and manifestations of PBC. Fatigue and pruritus, common complaints associated with PBC, are considered symptoms directly associated with the disease. The 3 most common extrahepatic conditions associated with PBC are sicca syndrome, thyroid disorders, and systemic sclerosis. PBC is also associated with a clustering of other autoimmune conditions (e.g., Raynaud phenomenon or scleroderma); however, a recent population-based study found that concomitant autoimmune conditions did not influence outcomes in patients with PBC (66). Other symptoms that are poorly characterized but reported by patients with PBC include restless leg syndrome, cognitive impairment, and bone and joint pain, the severity of which may not be proportionate to the severity of the underlying liver disease. Furthermore, chronic cholestasis associated with PBC may be associated with extrahepatic manifestations, such as hyperlipidemia, metabolic bone disease, and fat-soluble vitamin deficiencies. Patients with PBC can also experience impaired quality of life attributed to associated fatigue, cognitive symptoms, social and emotional dysfunction, sleep disturbances, and depression (67,68). PBC, primary biliary cholangitis.
Figure 3.
Figure 3.
Updated algorithm for the treatment of PBC. ∼sp100 Gp210. *Fenofibrate is not currently approved for the treatment of PBC and use is considered off-label. ALP, alkaline phosphatase; AMA, antimicrobial antibodies; ANA, antinuclear antibodies; CPC, Child-Pugh class; CSPH, clinically significant portal hypertension; HCC, hepatocellular carcinoma; MRE, magnetic resonance elastography; OCA, obeticholic acid; PBC, primary biliary cholangitis; TE, transient elastography; UDCA, ursodeoxycholic acid; VCTE, vibration-controlled transient elastography.
See this image and copyright information in PMC

References

    1. Murillo Perez CF, Goet JC, Lammers WJ, et al. Milder disease stage in patients with primary biliary cholangitis over a 44-year period: A changing natural history. Hepatology 2018;67:1920–30. - PubMed
    1. Younossi ZM, Bernstein D, Shiffman ML, et al. Diagnosis and management of primary biliary cholangitis. Am J Gastroenterol 2019;114:48–63. - PubMed
    1. Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2021 practice guidance update from the American association for the study of liver diseases. Hepatology 2021;75:1012–3. - PubMed
    1. EASL Clinical Practice Guidelines. The diagnosis and management of patients with primary biliary cholangitis. J Hepatol 2017;67:145–72. - PubMed
    1. Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American association for the study of liver diseases. Hepatology 2019;69:394–419. - PubMed

Publication types

MeSH terms

Substances