Targeting hepatic stellate cells to prevent or reverse liver fibrosis

Evidence that promoting HSC senescence reduces fibrogenesis is the rationale for exploring induction of senescence as a strategy for the treatment of liver fibrosis. However, it should be noted that accumulation of senescent hepatocytes may lead to hepatic dysfunction. This potential detrimental consequence requires a comprehensive evaluation of the effects of inducing HSC senescence in the liver. Furthermore, the interaction between senescent HSCs and immune cells, including macrophages, lymphocytes and NK cells, demonstrates that the elimination of senescent HSCs is determined to a large extent by immune cells. This indicates that maintaining the proper micro-environment in the liver is key to the success of immune clearance of senescent HSCs. Finally, in the end, inducers of senescence may only be successfully applied in combination with senolytics to minimize the disadvantages and detrimental effects of accumulated senescent cells. In conclusion, more studies should be conducted to clarify role of HSC senescence in liver fibrosis.