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E., Valiente, P

Targeting inflammation and fibrosis via chemokine receptors CCR2/CCR5 Macrophages have emerged as essential players in acute and chronic liver injury and in a wide range of liver diseases including NASH216 and more recently also PSC.217 Cenicriviroc (CVC) is a dual CCR2/CCR5 chemokine receptor antagonist that is able to block CCR2/5 on macrophages and HSC (figure 3) and is currently developed as anti-inflammatory/anti-fibrotic treatment in NASH and other indications.218 Despite encouraging interim data after 1 year,219 final analysis after 2 years revealed that a no significant antifibrotic effect in NASH (table 1).220 A long-term phase 3 study (AURORA, NCT03028740) was terminated early due to lack of efficacy, but CVC is still investigated in combination strategies (eg, FXR agonist tropifexor/TANDEM trial see above)

The activation of HSCs is due to several intracellular and extracellular events and signals, including oxidative stress and transforming growth factor Smad3 pathway activation

Although angiogenesis is very important for tendon healing, prolonged angiogenesis may result in prolonged/impaired healing and leads to chronic tendon disease