Antifibrotic Drugs

Massimo Pinzani MD, PhD

Department of Internal Medicine, Centre for Research, High Education and Transfer “DENOThe”, University of Florence, Italy

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Massimo Pinzani MD, PhD,

Massimo Pinzani MD, PhD

Department of Internal Medicine, Centre for Research, High Education and Transfer “DENOThe”, University of Florence, Italy

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Book Editor(s):Roberto de Franchis MD, AGAF,

Roberto de Franchis MD, AGAF

Professor of Gastroenterology Head

Department of Medical Sciences, University of Milan, and Gastroenterology 3 Unit, IRCCS Ca' Granda Ospedale Maggiore Policlinico Mangiagalli and Regina Elena Foundation, Milan, Italy

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First published: 17 November 2010

https://doi.org/10.1002/9781444393989.ch21

Summary

This chapter contains sections titled:

Introduction
General features of antifibrogenic agents
The potential antifibrogenic action of antiviral drugs
Angiotensin II receptor blockers
Antioxidants and “herbal” drugs
Probiotics and other strategies to modulate the gut flora: is it worth a try?
Antiangiogenic is also antifibrogenic
Compensated cirrhosis: the ideal ground for experimenting antifibrotic drugs
References

References

Pinzani M, Macias Barragan J (2010) An update on the pathophysiology of liver fibrosis. Expert Rev Gastroenterol Hepatol, 4: 459–72.
10.1586/egh.10.47
PubMed Web of Science® Google Scholar
Mazzocca A, Sciammetta SC, Carloni V, et al. (2005) Binding of hepatitis C virus envelope protein E2 to CD81 up-regulates matrix metalloproteinase-2 in human hepatic stellate cells. J Biol Chem 280: 11329–39.
10.1074/jbc.M410161200
CAS PubMed Web of Science® Google Scholar
Bruno R, Galastri S, Sacchi P, et al. (2010) The HIV envelope protein GP120 modulates the biology of human hepatic stellate cells: a link between HIV infection and liver fibrogenesis. Gut 59: 513–20.
10.1136/gut.2008.163287
CAS PubMed Web of Science® Google Scholar
Bataller R, Schwabe RF, Choi YH, et al. (2003) NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis. J Clin Invest 112: 1383–94.
10.1172/JCI18212
CAS PubMed Web of Science® Google Scholar
Oakley F, Teoh V, Ching-A-Sue G, et al. (2009) Angiotensin II activates IkappaB Kinase Phosphorylation of RelA at Ser(536) to promote myofibroblast survival and liver fibrosis. Gastroenterology 136: 2334–44.
10.1053/j.gastro.2009.02.081
CAS PubMed Web of Science® Google Scholar
Pinzani M (2009) Unraveling the spider web of hepatic stellate cell apoptosis. Gastroenterology 136: 2061–3.
10.1053/j.gastro.2009.04.033
CAS PubMed Web of Science® Google Scholar
Novo E, Marra F, Zamara E, et al. (2006) Overexpression of Bcl-2 by activated human hepatic stellate cells: resistance to apoptosis as a mechanism of progressive hepatic fibrogenesis in humans. Gut 55: 1174–82.
10.1136/gut.2005.082701
CAS PubMed Web of Science® Google Scholar
Colmenero J, Bataller R, Sancho-Bru P, et al. (2009) Effects of Losartan on hepatic expression of non-phagocytic NADPH oxidase and fibrogenic genes in patients with chronic hepatitis C. Am J Physiol Gastrointest Liver Physiol 297: G726–34.
10.1152/ajpgi.00162.2009
CAS PubMed Web of Science® Google Scholar
Novo E, Parola M (2008) Redox mechanisms in hepatic chronic wound healing and fibrogenesis. Fibrogenesis Tissue Repair 1: 5.
10.1186/1755-1536-1-5
CAS PubMed Google Scholar
Meneghin MD, Hogaboam C (2007) Infectious disease, the innate immune response, and fibrosis. J Clin Invest 117: 530–8.
10.1172/JCI30595
CAS PubMed Web of Science® Google Scholar
Akira S, Takeda K. (2004) Toll-like receptor signalling. Nat Rev Immunol 4: 499–511.
10.1038/nri1391
CAS PubMed Web of Science® Google Scholar
Otte JM, Rosenberg IM, Podolsky DK (2003) Intestinal myofibroblasts in innate immune responses of the intestine. Gastroenterology 124: 1866–78.
10.1016/S0016-5085(03)00403-7
CAS PubMed Web of Science® Google Scholar
Brun P, Castagliuolo I, Pinzani M, Palu G, Martines D (2005) Exposure to bacterial cell wall products triggers an inflammatory phenotype in hepatic stellate cells. Am J Physiol Gastrointest Liver Physiol 289: G571–8.
10.1152/ajpgi.00537.2004
CAS PubMed Web of Science® Google Scholar
Brun P, Castagliuolo I, Di Leo V, et al. (2007) Increased intestinal permeability in obese mice: new evidences in the pathogenesis of nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol 292: G518–25.
10.1152/ajpgi.00024.2006
CAS PubMed Web of Science® Google Scholar
Seki E, Brenner DA (2008) Toll-like receptors and adaptor molecules in liver disease: update. Hepatology 48: 322–35.
10.1002/hep.22306
CAS PubMed Web of Science® Google Scholar
Pinzani M, Rombouts K (2004) Liver fibrosis: from the bench to clinical targets. Dig Liver Dis 36: 231–42.
10.1016/j.dld.2004.01.003
CAS PubMed Web of Science® Google Scholar
Corpechot C, Barbu V, Wendum D, et al. (2002) Hypoxia-induced VEGF and collagen I expressions are associated with angiogenesis and fibrogenesis in experimental cirrhosis. Hepatology 35: 1010–21.
10.1053/jhep.2002.32524
CAS PubMed Web of Science® Google Scholar
DeLeve LD (2007) Hepatic microvasculature in liver injury. Semin Liver Dis 27: 390–400.
10.1055/s-2007-991515
CAS PubMed Web of Science® Google Scholar
Rosmorduc O, Wendum D, Corpechot C, et al. (1999) Hepatocellular hypoxia-induced vascular endothelial growth factor expression and angiogenesis in experimental biliary cirrhosis. Am J Pathol 155: 1065–73.
10.1016/S0002-9440(10)65209-1
CAS PubMed Web of Science® Google Scholar
Ankoma-Sey V, Matli M, Chang KB, et al. (1998) Coordinated induction of VEGF receptors in mesenchymal cell types during rat hepatic wound healing. Oncogene 17: 115–21.
10.1038/sj.onc.1201912
CAS PubMed Web of Science® Google Scholar
Aleffi S, Petrai I, Bertolani C, et al. (2005) Upregulation of proinflamma-tory and proangiogenic cytokines by leptin in human hepatic stellate cells. Hepatology 42: 1339–48.
10.1002/hep.20965
CAS PubMed Web of Science® Google Scholar
Wang YQ, Luk JM, Ikeda K, et al. (2004) Regulatory role of vHL/HIF-1alpha in hypoxia-induced VEGF production in hepatic stellate cells. Biochem Biophys Res Commun 317: 358–62.
10.1016/j.bbrc.2004.03.050
CAS PubMed Web of Science® Google Scholar
Novo E, Cannito S, Zamara E, et al. (2007) Proangiogenic cytokines as hypoxia-dependent factors stimulating migration of human hepatic stellate cells. Am J Pathol 170: 1942–53.
10.2353/ajpath.2007.060887
CAS PubMed Web of Science® Google Scholar
Tugues S, Fernandez-Varo G, Muñoz-Luque J, et al. (2007) Antiangiogenic treatment with sunitinib ameliorates inflammatory infiltrate, fibrosis, and portal pressure in cirrhotic rats. Hepatology 46: 1919–26.
10.1002/hep.21921
CAS PubMed Web of Science® Google Scholar
Mejias M, Garcia-Pras E, Tiani C, et al. (2009) Beneficial effects of sorafenib on splanchnic, intrahepatic, and portocollateral circulations in portal hyper-tensive and cirrhotic rats. Hepatology 49: 1245–56.
10.1002/hep.22758
CAS PubMed Web of Science® Google Scholar

Portal Hypertension V: Proceedings of the Fifth Baveno International Consensus Workshop, Fifth Edition