Clinical Management of Primary Biliary Cholangitis—Strategies and Evolving Trends

Lixia Gao, Li Wang, Elena Woo, Xiao Song He, Gao Xiang Yang, Christopher Bowlus, Patrick S.C. Leung, M. Eric Gershwin

Research output: Contribution to journalReview article

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.

Original languageEnglish (US)
JournalClinical Reviews in Allergy and Immunology
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Drug Delivery Systems
Bile Acids and Salts
Fibrosis
Inflammation
Therapeutics
Autoimmune Diseases
Disease Progression
Bezafibrate
Nanomedicine
Fenofibrate
Intrahepatic Bile Ducts
Peroxisome Proliferator-Activated Receptors
Cholestasis
Histocompatibility Antigens Class II
Immune System Diseases
Pruritus
Autoimmunity
Chemokines
Pharmaceutical Preparations
Liver Transplantation

Keywords

  • Clinical trial
  • Nanomedicine
  • Primary biliary cholangitis
  • Tolerogenic nanoparticle

ASJC Scopus subject areas

  • Immunology and Allergy

Cite this

Clinical Management of Primary Biliary Cholangitis—Strategies and Evolving Trends. / Gao, Lixia; Wang, Li; Woo, Elena; He, Xiao Song; Yang, Gao Xiang; Bowlus, Christopher; Leung, Patrick S.C.; Gershwin, M. Eric.

In: Clinical Reviews in Allergy and Immunology, 01.01.2019.

Research output: Contribution to journalReview article

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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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