Cellular senescence and its pathogenic and therapeutic implications in autoimmune hepatitis.

Abstract

Introduction: Senescent cells are characterized by replicative arrest and phenotypes that produce diverse pro-inflammatory and pro-oxidant mediators. The senescence of diverse hepatic cell types could constitute an unrecognized pathogenic mechanism and prognostic determinant in autoimmune hepatitis. The impact of cellular senescence in autoimmune hepatitis is unknown, and it may suggest adjunctive management strategies.

Areas covered: This review describes the molecular mechanisms of cellular senescence, indicates its diagnostic features, suggests its consequences, presents possible therapeutic interventions, and encourages investigations of its pathogenic role and management in autoimmune hepatitis. Treatment prospects include elimination or reversal of senescent cells, generation of ectopic telomerase, reactivation of dormant telomerase, neutralization of specific pro-inflammatory secretory products, and mitigation of the effects of mitochondrial dysfunction.

Expert opinion: The occurrence, nature, and consequences of cellular senescence in autoimmune hepatitis must be determined. The senescence of diverse hepatic cell types could affect the outcome of autoimmune hepatitis by impairing hepatic regeneration, intensifying liver inflammation, and worsening hepatic fibrosis. Cellular senescence could contribute to suboptimal responses during conventional glucocorticoid-based therapy. Interventions that target specific pro-inflammatory products of the senescent phenotype or selectively promote apoptosis of senescent cells may be preferred adjunctive treatments for autoimmune hepatitis depending on the cancer risk.