Evolving paradigm of treatment for autoimmune hepatitis

ABSTRACT

Introduction: Current medications for autoimmune hepatitis have broad anti-inflammatory and immunosuppressive actions, and their effects are short-lived and inconsistent. The goals of this review were to describe the actions and shortcomings of these medications, indicate the key pathogenic mechanisms that might be targeted by site-directed interventions, and present the pivotal studies supporting development of these alternative agents.

Areas covered: Abstracts cited in PubMed from April 1964 to February 2017 were identified using the search words ‘treatment of autoimmune hepatitis’. A secondary bibliography was developed from the references cited in selected articles, and additional searches were performed to expand the concepts developed in these articles. The number of abstracts reviewed exceeded 1000, and the number of full-length articles reviewed exceeded 100.

Expert commentary: Molecular, cellular, and pharmacological interventions that target key pathogenic pathways promise to change the current paradigm of treatment for autoimmune hepatitis. Interventions affecting lymphocyte activation, lymphocyte differentiation, effector cell migration, hepatocyte apoptosis, oxidative-nitrosative stress, fibrogenesis, and intestinal dysbiosis promise to emerge as supplemental or replacement therapies. The intestinal microbiome constitutes the next investigational frontier that may influence future management strategies. Unwanted and unexpected consequences of manipulating these homeostatic pathways constitute the major unmeasured risks of these evolving regimens.

KEYWORDS:

• Autoimmune hepatitis
• treatment
• pathogenic pathways
• site-directed interventions
• hepatic fibrosis

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

No funding was received.