查看文章

Background: Hepatic fat accumulation modulates innate immunity causing recruitment of bone marrow derived macrophages/activation of Kupffer cells, resulting in inflammatory changes associated with the development of insulin resistance and NASH. Monocyte recruitment/infiltration into the liver is mediated by CC chemokine receptor 2 (CCR2). CCR5 promotes obesity-induced insulin resistance/hepatic steatosis in murine models. Cenicriviroc (CVC) is an oral CCR2/CCR5 antagonist in Phase 3 development for NASH. We evaluated effects of CVC on inflammatory cytokines and HbA1c in NASH subjects.

Methods: Adults with NASH and liver fibrosis were randomized 1: 1 to CVC 150 mg or placebo (PBO)[Phase 2 CENTAUR study]. Cytokines and metabolic parameters were assessed.

Results: In 289 randomized adults (mean age 54 years, mean BMI 33.9 kg/m 2, 52.0% diabetes), CCL2 significantly increased …