Combination therapy for nonalcoholic steatohepatitis (NASH) and liver fibrosis

摘要

The present invention provides an effective amount of a CC chemokine receptor 5 (CCR5) antagonist (e.g., maraviroc or vicriviroc or cenicriviroc) and / or an effective amount of a CC chemokine receptor 2 (CCR2) antagonist. CCR5, such as nonalcoholic steatohepatitis (NASH), comprising administering a CCR5 / CCR2 antagonist with an amount, or an effective amount of a Panesoid X receptor (FXR) agonist (eg, obeticholic acid (OCA)) Or to a method of treating CCR2-mediated disease. An “effective amount” may be a regular clinical dose of each agent alone or a reduced dose of FXR receptor agonist and / or CCR5 / CCR2 antagonist. Combination may include (1) improved efficacy and (2) substantial reduction of side effects, in particular associated with administration of OCA or its analogs, ie, lower impact on increased liver enzymes, and (3) lower severity and frequency of pruritus It is effective in the treatment of NASH. Fixed dose combinations provide for better efficacy and safety profiles.