Treatments specifically focusing on the immunoin

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Treatments specifically focusing on the immunoinflammatory arm of NASH have also been evaluated, in particular Cenicriviroc (CVC). CVC is a dual CCR2 and CCR5 antagonist that has been shown to limit fibrosis without affecting other aspects of NASH in mice162,163. The chemokine receptors CCR2 and CCR5 are expressed by monocytes as well as T cells and CVC would thus be expected to limit immune cell infiltration of the liver during NASH. Although CVC showed promising results in phase II trials, the phase III study was recently terminated owing to a lack of efficacy11. This is particularly disappointing as CVC was at the frontline of approaches to limit fibrosis in patients with NASH, which is of particular importance as fibrosis can lead to permanent effects on the liver such as cirrhosis164. Thus, use of CVC might be combined with the blocking of other chemokine receptors controlling T cell recruitment to more efficiently limit NASH. Indeed, in addition to CCR2 and CCR5, T cell-specific chemokine receptors, such as CXCR3 or CXCR6, the latter being recently identified to mark a subset of NASH-associated autoaggressive CD8+ T cells116, could be targeted.

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