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Examining pathogenic concepts of autoimmune hepatitis for cues to future investigations and interventions.

Abstract：

:Multiple pathogenic mechanisms have been implicated in autoimmune hepatitis, but they have not fully explained susceptibility, triggering events, and maintenance or escalation of the disease. Furthermore, they have not identified a critical defect that can be targeted. The goals of this review are to examine the diverse pathogenic mechanisms that have been considered in autoimmune hepatitis, indicate investigational opportunities to validate their contribution, and suggest interventions that might evolve to modify their impact. English abstracts were identified in PubMed by multiple search terms. Full length articles were selected for review, and secondary and tertiary bibliographies were developed. Genetic and epigenetic factors can affect susceptibility by influencing the expression of immune regulatory genes. Thymic dysfunction, possibly related to deficient production of programmed cell death protein-1, can allow autoreactive T cells to escape deletion, and alterations in the intestinal microbiome may help overcome immune tolerance and affect gender bias. Environmental factors may trigger the disease or induce epigenetic changes in gene function. Molecular mimicry, epitope spread, bystander activation, neo-antigen production, lymphocytic polyspecificity, and disturbances in immune inhibitory mechanisms may maintain or escalate the disease. Interventions that modify epigenetic effects on gene expression, alter intestinal dysbiosis, eliminate deleterious environmental factors, and target critical pathogenic mechanisms are therapeutic possibilities that might reduce risk, individualize management, and improve outcome. In conclusion, diverse pathogenic mechanisms have been implicated in autoimmune hepatitis, and they may identify a critical factor or sequence that can be validated and used to direct future management and preventive strategies.

journal_name

World J Gastroenterol

journal_title

World journal of gastroenterology

authors

Czaja AJ

doi

10.3748/wjg.v25.i45.6579

subject

Has Abstract

pub_date

2019-12-07 00:00:00

pages

6579-6606

issue

eissn

1007-9327

issn

2219-2840

journal_volume

pub_type

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Examining pathogenic concepts of autoimmune hepatitis for cues to future investigations and interventions.