Clinical Management of Primary Biliary Cholangitis—Strategies and Evolving Trends

  • Lixia Gao
  • Li Wang
  • Elena Woo
  • XiaoSong He
  • GaoXiang Yang
  • Christopher Bowlus
  • Patrick S.C LeungEmail author
  • M. Eric GershwinEmail author


PBC is a chronic progressive autoimmune disorder involving the destruction of intrahepatic small bile ducts, cholestasis, fibrosis, and ultimately cirrhosis if left untreated. It is largely driven by the autoimmune response, but bile acids and the intestinal microbiota are implicated in disease progression as well. The only drugs licensed for PBC are UDCA and OCA. UDCA as a first-line and OCA as a second-line therapy are safe and effective, but the lack of response in a significant portion of patients and inadequate control of symptoms such as fatigue and pruritus remain as concerns. Liver transplantation is an end-stage therapy for many patients refractory to UDCA, which gives excellent survival rates but also moderate to high recurrence rates. The limited options for FDA-approved PBC therapies necessitate the development of alternative approaches. Currently, a wide variety of experimental drugs exist targeting immunological and physiological aspects of PBC to suppress inflammation. Immunological therapies include drugs targeting immune molecules in the B cell and T cell response, and specific cytokines and chemokines implicated in inflammation. Drugs targeting bile acids are also noteworthy as bile acids can perpetuate hepatic inflammation and lead to fibrosis over time. These include FXR agonists, ASBT inhibitors, and PPAR agonists such as bezafibrate and fenofibrate. Nonetheless, many of these drugs can only delay disease progression and fail to enhance patients’ quality of life. Nanomedicine shows great potential for treatment of autoimmune diseases, as it provides a new approach that focuses on tolerance induction rather than immunosuppression. Tolerogenic nanoparticles carrying immune-modifying agents can be engineered to safely and effectively target the antigen-specific immune response in autoimmune diseases. These may work well with PBC especially, given the anatomical features and immunological specificity of the disease. Nanobiological therapy is thus an area of highly promising research for future treatment of PBC.


Primary biliary cholangitis Clinical trial Nanomedicine Tolerogenic nanoparticle 



Primary biliary cholangitis


Ursodeoxycholic acid


Obeticholic acid


Alkaline phosphatase


Anti-mitochondrial antibody


Biliary epithelial cells


Bile acids


Food and Drug Administration


Nonalcoholic steatohepatitis


6 Alpha-ethyl-chenodeoxycholic acid


Chenodeoxycholic acid


Farnesoid X receptor


Cholesterol 7-alpha-hydroxylase


Fibroblast growth factor 19


Upper limit or normal


Liver transplantation


Lysophosphatidic acid




Ileal bile acid transporter


Apical sodium-dependent bile acid transporter


Pyruvate dehydrogenase complex-E2




Forkhead box P3


Transforming growth factor beta


Tumor necrosis factor alpha




Antigen-presenting cell


Cytotoxic T lymphocyte antigen-4


Regulatory T cells


Chemokine (C-X-C motif) ligand


Chemokine (C-X-C motif) receptor


B cell activating factor






Constitutive androstane receptor


Pregnane X receptor


Liver X receptor


Transmembrane G-protein-coupled receptor 5


G-protein-coupled bile acid receptor 1


Peroxisome proliferator-activated receptor


Norursodeoxycholic acid


Nuclear factor κB


Primary sclerosing cholangitis


Mouse mammary tumor virus




Gamma glutamyl transferase


Nicotinamide adenine dinucleotide phosphate hydrogen


Nicotinamide adenine dinucleotide phosphate hydrogen oxidase


Lysyl oxidase like 2


Tolerogenic nanoparticles


Tolerogenic immune-modifying nanoparticle


autoimmune encephalomyelitis




Myelin oligodendrocyte glycoprotein


Proteolipid protein




Granulocyte/macrophage-colony-stimulating factor


Dendritic cells


Recombinant human myelin basic protein


Type 1 diabetes


Aryl hydrocarbon receptor


2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester


Double strands DNA


Systemic lupus erythematosus


Type II collagen


Programmed death ligand 1




Monocyte chemoattractant protein 1


Chemokine CX3C motif receptor 1


Major histocompatibility complex


Mesenchymal stem cell


Multidrug resistance protein 3


Compliance with Ethical Standards

Conflict of Interest

The authors do not have any conflict of interest on this paper.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Rheumatology and ImmunologyThe Second Hospital of Hebei Medical UniversityShijiazhuangChina
  2. 2.Division of Rheumatology, Allergy and Clinical Immunology, School of MedicineUniversity of California, DavisDavisUSA
  3. 3.Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital (PUMCH)Chinese Academy of Medical ScienceBeijingChina
  4. 4.Division of Gastroenterology and Hepatology, School of MedicineUniversity of CaliforniaDavisUSA

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