Review article: next-generation transformative advances in the pathogenesis and management of autoimmune hepatitis

Background: Advances in autoimmune hepatitis that transform current concepts of pathogenesis and management can be anticipated as products of ongoing investigations driven by unmet clinical needs and an evolving biotechnology. Aim: To describe the advances that are likely to become transformative in autoimmune hepatitis, based on the direction of current investigations. Methods: Pertinent abstracts were identified in PubMed by multiple search terms. Full-length articles were selected for review, and a secondary bibliography was developed. The discovery process was repeated, and a tertiary bibliography was identified. The number of abstracts reviewed was 2830, and the number of full-length articles reviewed exceeded 150. Results: Risk-laden allelic variants outside the major histocompatibility complex (rs3184504, r36000782) are being identified by genome-wide association studies, and their gene products are potential therapeutic targets. Epigenetic changes associated with environmental cues can enhance the transcriptional activity of genes, and chromatin re-structuring and antagonists of noncoding molecules of ribonucleic acid are feasible interventions. The intestinal microbiome is a discovery field for microbial products and activated immune cells that may translocate to the periphery and respond to manipulation. Epidemiological studies and controlled interview-based surveys may implicate environmental and xenobiotic factors that warrant evidence-based changes in lifestyle, and site-directed molecular and cellular interventions promise to change the paradigm of treatment from one of blanket immunosuppression. Conclusions: Advances in genetics, epigenetics, pathophysiology, epidemiology, and site-directed molecular and cellular interventions constitute the next generation of transformative advances in autoimmune hepatitis.