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Clinical Management of Primary Biliary Cholangitis-Strategies and Evolving Trends.

Authors
  • Gao, Lixia1, 2
  • Wang, Li3
  • Woo, Elena2
  • He, XiaoSong2
  • Yang, GaoXiang2
  • Bowlus, Christopher4
  • Leung, Patrick S C5
  • Gershwin, M Eric6
  • 1 Department of Rheumatology and Immunology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China. , (China)
  • 2 Division of Rheumatology, Allergy and Clinical Immunology, School of Medicine, University of California, Davis, 451 Health Sciences Drive, Suite 6510, Davis, CA, 95616, USA.
  • 3 Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Science, Beijing, China. , (China)
  • 4 Division of Gastroenterology and Hepatology, School of Medicine, University of California, Davis, CA, 95616, USA.
  • 5 Division of Rheumatology, Allergy and Clinical Immunology, School of Medicine, University of California, Davis, 451 Health Sciences Drive, Suite 6510, Davis, CA, 95616, USA. [email protected]
  • 6 Division of Rheumatology, Allergy and Clinical Immunology, School of Medicine, University of California, Davis, 451 Health Sciences Drive, Suite 6510, Davis, CA, 95616, USA. [email protected]
Type
Published Article
Journal
Clinical Reviews in Allergy & Immunology
Publisher
Springer-Verlag
Publication Date
Oct 01, 2020
Volume
59
Issue
2
Pages
175–194
Identifiers
DOI: 10.1007/s12016-019-08772-7
PMID: 31713023
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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.

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