An update on the recent advances in antifibrotic therapy
Frank Tacke & Ralf Weiskirchen ORCID Icon
Received 09 May 2018, Accepted 26 Sep 2018, Accepted author version posted online: 27 Sep 2018, Published online: 03 Oct 2018
Introduction: Chronic injury to the liver, such as viral hepatitis, alcoholism, non-alcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH), promotes extracellular matrix deposition and organ scarring, termed hepatic fibrosis. Fibrosis might progress to cirrhosis and predisposes to hepatocellular carcinoma (HCC), but is also associated with extrahepatic morbidity and mortality in NAFLD/NASH. The improved understanding of pathogenic mechanisms underlying chronic inflammation and fibrogenesis in the liver prompted recent advances in antifibrotic therapies.
Areas covered: We review recent advances in antifibrotic therapy, of which most are currently tested in clinical trials for NAFLD or NASH. This explains the manifold metabolic pathways as antifibrotic targets, including farnesoid X receptor (FXR) agonism (obeticholic acid, nonsteroidal FXR agonists), acetyl-CoA carboxylase inhibition, peroxisome proliferator-activator receptor agonism (elafibranor, lanifibranor, saroglitazar), and fibroblast growth factor (FGF)-21 or FGF-19 activation. Other antifibrotic drug candidates target cell death or inflammation, such as caspase (emricasan) or ASK1 inhibitors (selonsertib), galectin-3 inhibitors and reducing inflammatory macrophage recruitment by blocking chemokine receptors CCR2/CCR5 (cenicriviroc).
Expert commentary: The tremendous advances in translational and clinical research fuels the hope for efficacious antifibrotic therapies within the next 5 years. Very likely, a combination of etiology-specific, metabolic, anti-inflammatory, and direct antifibrotic interventions will be most effective.
KEYWORDS: Liver fibrosis, macrophages, chemokine, matrix, regression, NAFLD/NASH, translational medicine, hepatic stellate cell, myofibroblast, gut-liver axis, microbiome作者: StephenW 时间: 2018-10-4 20:55
关于抗纤维化治疗最新进展的最新进展
Frank Tacke和Ralf Weiskirchen ORCID Icon
2018年5月9日收到，2018年9月26日接受，接受作者版本在线发布：2019年9月27日，在线发布：2018年10月3日
