Abstract
Cirrhosis represents the end-stage consequence of fibrosis of the hepatic parenchyma resulting in nodule formation and altered hepatic function. Mounting evidence has now established that even advanced fibrosis and cirrhosis are reversible. Examples include alcohol abstinence, lamivudine treatment for chronic hepatitis B1, treatment of hepatitis C with interferon/ ribavirin2, surgical decompression of biliary obstruction3, 4, immunosuppressive therapy for autoimmune hepatitis, and phlebotomy for hemochromatosis. Fibrosis and cirrhosis represent the consequences of a sustained wound-healing response to chronic liver injury from a variety of causes. Cirrhosis affects hundreds of millions of patients worldwide. In the USA, it is the most common non-neoplastic cause of death among hepatobiliary and digestive diseases, accounting for approximately 30000 deaths per year. In addition 10 000 deaths occur due to liver cancer, the majority of which arise in cirrhotic livers, with mortality rate steadily rising5, 6.
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References
Dienstag JL. Goldin RD, Heathcote EJ et al.Histological outcome during long-term lamivudine therapy. Gastroenterology. 2003;124:105–17.
Poynard T, McHutchison J, Manns M et al. Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology. 2002;122: 1303–13.
Bonis PA, Friedman SL, Kaplan MM. Is liver fibrosis reversible? N Engl J Med. 2001;344:452–4.
Hammel P, Couvelard A, O’Toole D et al. Regression of liver fibrosis after biliary drainage in patients with chronic pancreatitis and stenosis of the common bile duct. N Engl J Med. 2001;344:418–23.
El-Serag HB, Mason AC. Risk factors for the rising rates of primary liver cancer in the United States. Arch Intern Med. 2000;160:3227–30.
Befeler AS, Di Bisceglie AM. Hepatocellular carcinoma: diagnosis and treatment. Gastroenterology. 2002;122:1609–19.
Rojkind M, Giambrone MA, Biempica L. Collagen types in normal and cirrhotic liver. Gastroenterology. 1979;76:710–19.
Sims D. Recent advances in pericyte biology and implications for health and disease. Can J Cardiol. 1991;7:431–43.
Pinzani M, Failli P, Ruocco C et al. Fat-storing cells as liver-specific pericytcs. Spatial dynamics of agonist-stimulated intracellular calcium transients. J Clin Invest. 1992;90:642–6.
Bauer M, Paquette N, Zhang J et al. Chronic ethanol consumption increases hepatic sinusoidal contractile response to endothelin-1 in rat. Hepatology. 1994;22:1565.
Bauer M, Zhang J, Bauer I et al. ET-l induced alterations of hepatic microcirculation: sinusoidal and extra sinusoidal sites of actions. Am J Physiol. 1994;267:143–9.
Bhathal P, Grossman H. Reduction of the increased portal vascular resistance of the isolated perfused cirrhotic rat liver by vasodilators. J Hepatol. 1985;1:325–37.
Okumura S, Takei Y, Kawano S. Vasoactive effect of endothelin-1 on rat liver in vivo. Hepatology. 1994;19:155–61.
Geerts A. History and heterogeneity of stellate cells, and role in normal liver function. Semin Liver Dis. 2001;21:311–36.
Friedman SL. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Bioi Chern. 2000;275:2247–50.
Tsukamoto H, Horne W, Kamimura S et al. Experimental liver cirrhosis induced by alcohol and iron. J Clin Invest. 1995;96:620–30.
Jarnagin WR, Rockey DC, Kotcliansky VE, Wang SS, Bissell OM. Expression of variant fibronectins in wound healing: cellular source and biological activity of the EIIIA segment in rat hepatic fibrogenesis. J Cell Biol. 1994;127:2037–48.
Shi Z, Wakil AE, Rockey DC. Strain-specific differences in mouse hepatic wound healing are mediated by divergent T helper cytokine responses. Proc Natl Acad Sci USA. 1997; 94: 10663–8.
Benhamou Y, Di Martino V, Bochet M et al. Factors affecting liver fibrosis in human immunodeficiency virus-and hepatitis C virus-coinfected patients: impact of protease inhibitor therapy. Hepatology. 2001;34:283–7.
Schluger LK, Sheiner PA, Thung SN et al. Severe recurrent cholestatic hepatitis C following orthotopic liver transplantation. Hepatology. 1996;23:971–6.
Schwabe RF, Schnabl B, Kweon YO, Brenner DA. CD40 activates NF-kappa Band c-Jun N-terminal kinase and enhances chemokine secretion on activated human hepatic stellate cells. J Immunol. 2001;166:6812–19.
Ikeda K, Wang LH, Torres R et al. Discoidin domain receptor 2 interacts with Src and Shc following its activation by type I collagen. J Biol Chem. 2002;277:19206–12.
Olaso E, Ikeda K, Eng FJ et al. DDR2 receptor promotes MMP-2-mediated proliferation and invasion by hepatic stellate cells. J Clin Invest. 2001;108:1369–78.
Olaso E, Labrador JP, Wang L et al. Discoidin domain receptor 2 regulates fibroblast proliferation and migration through the extracellular matrix in association with transcriptional activation of matrix metalloproteinase-2. J Biol Chern. 2002;277:3606–13.
Benyon D, Arthur MJP. Extracellular matrix degradation and the role of stellate cells. Semin Liver Dis. 2001;21:373–84.
Iredale JP. Stellate cell behavior during resolution of liver injury. Semin Liver Dis. 2001;21:427–36.
Pinzani M, Marra F. Cytokine receptors and signaling during stellate cell activation. Semin Liver Dis. 2001;21:397–416.
Rockey DC. Vascular mediators in the injured liver. Hepatology. 2003;37:4–12.
Gressner AM, Weiskirchen R, Breitkopf K, Dooley S. Roles of tgf-beta in hepatic fibrosis. Front Biosci. 2002;7:D793–807.
Paradis V, Dargere D, Bonvoust F, Vidaud M, Segarini P, Bedossa P. Effects and regulation of connective tissue growth factor on hepatic stellate cells. Lab Invest. 2002;82:767–74.
Marra F. Chemokines in liver inflammation and fibrosis. Front Biosci. 2002;7:d1899–914.
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Friedman, S.L. (2004). Mechanisms of hepatic fibrogenesis. In: Groszmann, R.J., Bosch, J. (eds) Portal Hypertension in the 21st Century. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-1042-9_4
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DOI: https://doi.org/10.1007/978-94-007-1042-9_4
Publisher Name: Springer, Dordrecht
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