Recent clinical studies comprising patients successfully treated for viral hepatitis have shown that liver fibrogenesis may be reverted, even at later stages including during bridging fibrosis and cirrhosis. Intensive research has identified numerous potential novel targets in liver disease. Multiple innovative compounds have now entered clinical trials, mostly in non-alcoholic steatohepatitis (NASH) and NASH-associated cirrhosis due to their outstanding epidemiological relevance. In general, regression from liver fibrosis follows four major mechanistic principles: termination of chronic damage, shifting the cellular bias from inflammation to resolution, deactivation of myofibroblasts and direct matrix degradation. Obeying these principles, several promising approaches are currently evaluated, for example, targeting inflammatory macrophages via inhibition of chemokine CCL2, its receptor CCR2 or galectin-3, bone marrow-derived cell transfer, or antibodies against matrix-stabilizing lysyl oxidase-like-2. The ongoing trials will reveal which of the many potential targets prove to have clinical efficacy, bearing in mind that fibrosis reversibility is less likely to be achieved in humans than in animal models.
Keywords: chemokine; hepatic stellate cell; liver fibrosis; macrophages; matrix; regression.