Autoimmune hepatitis: Current and future therapies

Abstract

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that can lead to cirrhosis and liver failure. AIH can present in all ages, races, and ethnicities, but it predominantly affects women. As a heterogeneous disease, AIH presents variably in different patients, making diagnosis and treatment a challenge. Currently, the standard treatment for AIH comprises immunosuppressants; however, their long-term use is associated with adverse effects. The pathogenesis of AIH is complex, involving T cells, macrophages, and plasma cells that invade the periportal parenchyma and lead to an inflammatory cascade that can result in liver damage. Due to the complexity of AIH pathogenesis, treatment targets several inflammatory pathways. However, unlike other autoimmune diseases in which targeted treatments have been approved, there has been little progress made in advancing the treatment paradigm for AIH. Major obstacles to progress include challenges in conducting clinical trials, particularly patient recruitment and ensuring a diverse range of backgrounds; poorly defined outcomes to assess treatment response and improved quality of life; and a lack of study designs that account for the stage of disease and variations in treatment. A focus on individualized and steroid-free treatment approaches is needed to improve AIH prognosis and minimize steroid-associated adverse effects.

Graphical abstract

FIGURE 1

Potential targets for treatment of autoimmune hepatitis. Reprinted from Herkel J, et al. J Hepatol. 2020;73(2):446-448. Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. Abbreviations: APC, Ag-presenting cell; BAFF, B-cell activating factor; CD, cluster of differentiation; DC, dendritic cell; NK, natural killer; NKT, natural killer T-cell; PC, plasma cell; PRF, platelet rich fibrin; TGFβ, transforming growth factor beta; Th, T helper; TLR, toll-like receptor; Treg, regulatory T cell.