Evolving paradigm of treatment for autoimmune hepatitis

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.