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Editorial

Targeting CCR2/5 in the treatment of nonalcoholic steatohepatitis (NASH) and fibrosis: opportunities and challenges

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Pages 89-92 | Received 15 Jan 2020, Accepted 15 Jan 2020, Published online: 20 Jan 2020

References

  • Younossi Z, Anstee QM, Marietti M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Clin Pract Gastroenterol Hepatol. 2018;15(1):11–20.
  • Dulai PS, Singh S, Patel J, et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis. Hepatology. 2017;65(5):1557–1565.
  • Tacke F. Cenicriviroc for the treatment of non-alcoholic steatohepatitis and liver fibrosis. Expert Opin Investig Drugs. 2018;27(3):301–311.
  • Lefere S, Tacke F. Macrophages in obesity and non-alcoholic fatty liver disease: crosstalk with metabolism. JHEP Rep. 2019;1(1):30–43.
  • Devisscher L, Verhelst X, Colle I, et al. The role of macrophages in obesity-driven chronic liver disease. J Leukoc Biol. 2016;99(5):693–698.
  • Krenkel O, Puengel T, Govaere O, et al. Therapeutic inhibition of inflammatory monocyte recruitment reduces steatohepatitis and liver fibrosis. Hepatology. 2018;67(4):1270–1283.
  • Tsuchida T, Friedman SL. Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol. 2017;14(7):397–411.
  • Lefebvre E, Moyle G, Reshef R, et al. Antifibrotic effects of the dual CCR2/CCR5 antagonist cenicriviroc in animal models of liver and kidney fibrosis. PloS One. 2016;11(6):e0158156.
  • Baeck C, Wehr A, Karlmark KR, et al. Pharmacological inhibition of the chemokine CCL2 (MCP-1) diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury. Gut. 2012;61(3):416–426.
  • Ambade A, Lowe P, Kodys K, et al. Pharmacological inhibition of CCR2/5 signaling prevents and reverses alcohol-induced liver damage, steatosis, and inflammation in mice. Hepatology. 2019;69(3):1105–1121.
  • Ramachandran P, Dobie R, Wilson-Kanamori JR, et al. Resolving the fibrotic niche of human liver cirrhosis at single-cell level. Nature. 2019;575:512–518.
  • Baeck C, Wei X, Bartneck M, et al. Pharmacological inhibition of the chemokine C-C motif chemokine ligand 2 (monocyte chemoattractant protein 1) accelerates liver fibrosis regression by suppressing Ly-6C(+) macrophage infiltration in mice. Hepatology. 2014;59(3):1060–1072.
  • Seki E, De Minicis S, Gwak GY, et al. CCR1 and CCR5 promote hepatic fibrosis in mice. J Clin Invest. 2009;119(7):1858–1870.
  • Berres ML, Koenen RR, Rueland A, et al. Antagonism of the chemokine Ccl5 ameliorates experimental liver fibrosis in mice. J Clin Invest. 2010;120(11):4129–4140.
  • Coppola N, Perna A, Lucariello A, et al. Effects of treatment with maraviroc a CCR5 inhibitor on a human hepatic stellate cell line. J Cell Physiol. 2018;233(8):6224–6231.
  • Friedman SL, Ratziu V, Harrison SA, et al. A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis. Hepatology. 2018;67(5):1754–1767.
  • Rinella ME, Tacke F, Sanyal AJ, et al. Report on the AASLD/EASL joint workshop on clinical trial endpoints in NAFLD. J Hepatol. 2019;71(4):823–833.
  • Gale JD, Gilbert S, Blumenthal S, et al. Effect of PF-04634817, an oral CCR2/5 chemokine receptor antagonist, on albuminuria in adults with overt diabetic nephropathy. Kidney Int Rep. 2018;3(6):1316–1327.
  • Gale JD, Berger B, Gilbert S, et al. A CCR2/5 inhibitor, PF-04634817, is inferior to monthly ranibizumab in the treatment of diabetic macular edema. Invest Ophthalmol Vis Sci. 2018;59(6):2659–2669.
  • Lefebvre E, Gottwald M, Lasseter K, et al. Pharmacokinetics, safety, and CCR2/CCR5 Antagonist activity of Cenicriviroc in participants with mild or moderate Hepatic impairment. Clin Transl Sci. 2016;9(3):139–148.
  • Li X, Yao W, Yuan Y, et al. Targeting of tumour-infiltrating macrophages via CCL2/CCR2 signalling as a therapeutic strategy against hepatocellular carcinoma. Gut. 2017;66(1):157–167.
  • Teng KY, Han J, Zhang X, et al. Blocking the CCL2-CCR2 axis using CCL2-neutralizing antibody is an effective therapy for hepatocellular cancer in a mouse model. Mol Cancer Ther. 2017;16(2):312–322.
  • Mohs A, Kuttkat N, Reissing J, et al. Functional role of CCL5/RANTES for HCC progression during chronic liver disease. J Hepatol. 2017;66(4):743–753.
  • Bai H, Weng Y, Bai S, et al. CCL5 secreted from bone marrow stromal cells stimulates the migration and invasion of Huh7 hepatocellular carcinoma cells via the PI3K-Akt pathway. Int J Oncol. 2014;45(1):333–343.
  • Barashi N, Weiss ID, Wald O, et al. Inflammation-induced hepatocellular carcinoma is dependent on CCR5 in mice. Hepatology. 2013;58(3):1021–1030.

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