Translating an understanding of the pathogenesis of hepatic fibrosis to novel therapies

Clinical Gastroenterology and Hepatology

Volumn 11, Issue 3, 2013, Pages

  Rockey, Don C ^a  

^a MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

Cirrhosis; Fibrogenesis; Injury; Scar; Tissue; Wound Healing

Indexed keywords

ALPHA TOCOPHEROL; ANGIOTENSIN II; ANGIOTENSIN RECEPTOR ANTAGONIST; ANTIFIBROTIC AGENT; COLCHICINE; ENDOTHELIN 1; FARGLITAZAR; FIBROBLAST GROWTH FACTOR; HERBACEOUS AGENT; INTERLEUKIN 1; INTERLEUKIN 4; INTERLEUKIN 6; LEPTIN; LIPOPOLYSACCHARIDE; NORADRENALIN; PENTOXIFYLLINE; PLACEBO; POLYENE PHOSPHATIDYLCHOLINE; RECOMBINANT GAMMA INTERFERON; ROSIGLITAZONE; S ADENOSYLMETHIONINE; SILYMARIN; THROMBIN; THROMBOSPONDIN; TRANSFORMING GROWTH FACTOR ALPHA; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA INHIBITOR; UNCLASSIFIED DRUG; URSODEOXYCHOLIC ACID;

ARTICLE; AUTOIMMUNE HEPATITIS; CELL ACTIVATION; CELL PROLIFERATION; EPITHELIAL MESENCHYMAL TRANSITION; FATTY LIVER; FIBROGENESIS; HEPATITIS B; HEPATITIS C; HUMAN; LIVER CIRRHOSIS; LIVER FIBROSIS; LIVER INJURY; NONALCOHOLIC FATTY LIVER; PATHOGENESIS; PATHOPHYSIOLOGY; PATIENT MONITORING; SALVIA; STELLATE CELL; TREATMENT RESPONSE; VIRUS INHIBITION; WOUND HEALING;

EID: 84874574154     PISSN: 15423565     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cgh.2013.01.005     Document Type: Article

References (178)

1. Jarnagin W.R., Rockey D.C., Koteliansky V.E., et al. Expression of variant fibronectins in wound healing: cellular source and biological activity of the EIIIA segment in rat hepatic fibrogenesis. J Cell Biol 1994, 127:2037-2048.
2. Schuppan D. Structure of the extracellular matrix in normal and fibrotic liver: collagens and glycoproteins. Semin Liver Dis 1990, 10:1-10.
3. Rockey D.C. The cell and molecular biology of hepatic fibrogenesis. Clinical and therapeutic implications. Clin Liver Dis 2000, 4:319-355.
4. Rockey D.C. Antifibrotic therapy in chronic liver disease. Clin Gastroenterol Hepatol 2005, 3:95-107.
5. Iredale J.P., Benyon R.C., Pickering J., et al. Mechanisms of spontaneous resolution of rat liver fibrosis. Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors. J Clin Invest 1998, 102:538-549.
6. Rockey D.C., Chung J.J. Endothelin antagonism in experimental hepatic fibrosis. Implications for endothelin in the pathogenesis of wound healing. J Clin Invest 1996, 98:1381-1388.
7. Lai C.L., Chien R.N., Leung N.W., et al. A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group. N Engl J Med 1998, 339:61-68.
8. 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, 122:1303-1313.
9. Hadziyannis S.J., Tassopoulos N.C., Heathcote E.J., et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B. N Engl J Med 2003, 348:800-807.
10. Ellis E.L., Mann D.A. Clinical evidence for the regression of liver fibrosis. J Hepatol 2012, 56:1171-1180.
11. Bruno S., Crosignani A., Facciotto C., et al. Sustained virologic response prevents the development of esophageal varices in compensated, Child-Pugh class A hepatitis C virus-induced cirrhosis. A 12-year prospective follow-up study. Hepatology 2010, 51:2069-2076.
12. Mallet V., Gilgenkrantz H., Serpaggi J., et al. Brief communication: the relationship of regression of cirrhosis to outcome in chronic hepatitis C. Ann Intern Med 2008, 149:399-403.
13. Czaja A.J., Carpenter H.A. Decreased fibrosis during corticosteroid therapy of autoimmune hepatitis. J Hepatol 2004, 40:646-652.
14. Liaw Y.F., Sung J.J., Chow W.C., et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004, 351:1521-1531.
15. 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, 344:418-423.
16. Wanless I.R., Nakashima E., Sherman M. Regression of human cirrhosis. Morphologic features and the genesis of incomplete septal cirrhosis. Arch Pathol Lab Med 2000, 124:1599-1607.
17. Dufour J.F., DeLellis R., Kaplan M.M. Reversibility of hepatic fibrosis in autoimmune hepatitis. Ann Intern Med 1997, 127:981-985.
18. Rockey D.C. Hepatic fibrosis, stellate cells, and portal hypertension. Clin Liver Dis 2006, 10:459-479. vii-viii.
19. Li Z., Dranoff J.A., Chan E.P., et al. Transforming growth factor-beta and substrate stiffness regulate portal fibroblast activation in culture. Hepatology 2007, 46:1246-1256.
20. Kisseleva T., Uchinami H., Feirt N., et al. Bone marrow-derived fibrocytes participate in pathogenesis of liver fibrosis. J Hepatol 2006, 45:429-438.
21. Kalluri R., Neilson E.G. Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest 2003, 112:1776-1784.
22. Kaimori A., Potter J., Kaimori J.Y., et al. Transforming growth factor-beta1 induces an epithelial-to-mesenchymal transition state in mouse hepatocytes in vitro. J Biol Chem 2007, 282:22089-22101.
23. Wake K. Perisinusoidal stellate cells (fat-storing cells, interstitial cells, lipocytes), their related structure in and around the liver sinusoids, and vitamin A-storing cells in extrahepatic organs. Int Rev Cytol 1980, 66:303-353.
24. Blomhoff R., Wake K. Perisinusoidal stellate cells of the liver: important roles in retinol metabolism and fibrosis. FASEB J 1991, 5:271-277.
25. Maher J.J., McGuire R.F. Extracellular matrix gene expression increases preferentially in rat lipocytes and sinusoidal endothelial cells during hepatic fibrosis in vivo. J Clin Invest 1990, 86:1641-1648.
26. Rockey D.C., Boyles J.K., Gabbiani G., et al. Rat hepatic lipocytes express smooth muscle actin upon activation in vivo and in culture. J Submicrosc Cytol Pathol 1992, 24:193-203.
27. Hinz B. Masters and servants of the force: the role of matrix adhesions in myofibroblast force perception and transmission. Eur J Cell Biol 2006, 85:175-181.
28. Gabbiani G. The myofibroblast in wound healing and fibrocontractive diseases. J Pathol 2003, 200:500-503.
29. Aleffi S., Petrai I., Bertolani C., et al. Upregulation of proinflammatory and proangiogenic cytokines by leptin in human hepatic stellate cells. Hepatology 2005, 42:1339-1348.
30. Santamato A., Fransvea E., Dituri F., et al. Hepatic stellate cells stimulate HCC cell migration via laminin-5 production. Clin Sci (Lond) 2011, 121:159-168.
31. Gentilini A., Rombouts K., Galastri S., et al. Role of the stromal-derived factor-1 (SDF-1)-CXCR4 axis in the interaction between hepatic stellate cells and cholangiocarcinoma. J Hepatol 2012, 57:813-820.
32. Bonacchi A., Petrai I., Defranco R.M., et al. The chemokine CCL21 modulates lymphocyte recruitment and fibrosis in chronic hepatitis C. Gastroenterology 2003, 125:1060-1076.
33. Sanderson N., Factor V., Nagy P., et al. Hepatic expression of mature transforming growth factor beta 1 in transgenic mice results in multiple tissue lesions. Proc Natl Acad Sci U S A 1995, 92:2572-2576.
34. Hellerbrand C., Stefanovic B., Giordano F., et al. The role of TGFbeta1 in initiating hepatic stellate cell activation in vivo. J Hepatol 1999, 30:77-87.
35. Schnabl B., Kweon Y.O., Frederick J.P., et al. The role of Smad3 in mediating mouse hepatic stellate cell activation. Hepatology 2001, 34:89-100.
36. Friedman S.L., Maher J.J., Bissell D.M. Mechanisms and therapy of hepatic fibrosis: report of the AASLD Single Topic Basic Research Conference. Hepatology 2000, 32:1403-1408.
37. Bissell D.M., Wang S.S., Jarnagin W.R., et al. Cell-specific expression of transforming growth factor-beta in rat liver. Evidence for autocrine regulation of hepatocyte proliferation. J Clin Invest 1995, 96:447-455.
38. Yata Y., Gotwals P., Koteliansky V., et al. Dose-dependent inhibition of hepatic fibrosis in mice by a TGF-beta soluble receptor: implications for antifibrotic therapy. Hepatology 2002, 35:1022-1030.
39. Khimji A.K., Shao R., Rockey D.C. Divergent transforming growth factor-beta signaling in hepatic stellate cells after liver injury: functional effects on ECE-1 regulation. Am J Pathol 2008, 173:716-727.
40. Huang G., Brigstock D.R. Regulation of hepatic stellate cells by connective tissue growth factor. Front Biosci 2012, 17:2495-2507.
41. Tong Z., Chen R., Alt D.S., et al. Susceptibility to liver fibrosis in mice expressing a connective tissue growth factor transgene in hepatocytes. Hepatology 2009, 50:939-947.
42. Saxena N.K., Saliba G., Floyd J.J., et al. Leptin induces increased alpha2(I) collagen gene expression in cultured rat hepatic stellate cells. J Cell Biochem 2003, 89:311-320.
43. Bataller R., Schwabe R.F., Choi Y.H., et al. NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis. J Clin Invest 2003, 112:1383-1394.
44. Bataller R., Gäbele E., Parsons C.J., et al. Systemic infusion of angiotensin II exacerbates liver fibrosis in bile duct-ligated rats. Hepatology 2005, 41:1046-1055.
45. Rockey D.C. Vascular mediators in the injured liver. Hepatology 2003, 37:4-12.
46. Oben J.A., Roskams T., Yang S., et al. Hepatic fibrogenesis requires sympathetic neurotransmitters. Gut 2004, 53:438-445.
47. Rockey D.C., Chung J.J. Interferon gamma inhibits lipocyte activation and extracellular matrix mRNA expression during experimental liver injury: implications for treatment of hepatic fibrosis. J Investig Med 1994, 42:660-670.
48. Inagaki Y., Nemoto T., Kushida M., et al. Interferon alfa down-regulates collagen gene transcription and suppresses experimental hepatic fibrosis in mice. Hepatology 2003, 38:890-899.
49. Kamada Y., Tamura S., Kiso S., et al. Enhanced carbon tetrachloride-induced liver fibrosis in mice lacking adiponectin. Gastroenterology 2003, 125:1796-1807.
50. Ueki T., Kaneda Y., Tsutsui H., et al. Hepatocyte growth factor gene therapy of liver cirrhosis in rats. Nat Med 1999, 5:226-230.
51. Kawada N., Kristensen D.B., Asahina K., et al. Characterization of a stellate cell activation-associated protein (STAP) with peroxidase activity found in rat hepatic stellate cells. J Biol Chem 2001, 276:25318-25323.
52. Friedman S.L., Roll F.J., Boyles J., et al. Maintenance of differentiated phenotype of cultured rat hepatic lipocytes by basement membrane matrix. J Biol Chem 1989, 264:10756-10762.
53. Gaca M.D.A., Georges P., Jammey P., et al. Matrix compliance determines hepatic stellate cell phenotype. Hepatology 2003, 38:776A.
54. Olsen A.L., Bloomer S.A., Chan E.P., et al. Hepatic stellate cells require a stiff environment for myofibroblastic differentiation. Am J Physiol Gastrointest Liver Physiol 2011, 301:G110-G118.
55. Racine-Samson L., Rockey D.C., Bissell D.M. The role of alpha1beta1 integrin in wound contraction. A quantitative analysis of liver myofibroblasts in vivo and in primary culture. J Biol Chem 1997, 272:30911-30917.
56. Shafiei M.S., Rockey D.C. The role of integrin-linked kinase in liver wound healing. J Biol Chem 2006, 281:24863-24872.
57. Shafiei M.S., Rockey D.C. The function of integrin-linked kinase in normal and activated stellate cells: implications for fibrogenesis in wound healing. Lab Invest 2012, 92:305-316.
58. Arthur M.J. Fibrogenesis II. Metalloproteinases and their inhibitors in liver fibrosis. Am J Physiol Gastrointest Liver Physiol 2000, 279:G245-G249.
59. Han Y.P., Zhou L., Wang J., et al. Essential role of matrix metalloproteinases in interleukin-1-induced myofibroblastic activation of hepatic stellate cell in collagen. J Biol Chem 2004, 279:4820-4828.
60. Han Y.P. Matrix metalloproteinases, the pros and cons, in liver fibrosis. J Gastroenterol Hepatol 2006, 21(Suppl 3):S88-S91.
61. Garcia-Bañuelos J., Siller-Lopez F., Miranda A., et al. Cirrhotic rat livers with extensive fibrosis can be safely transduced with clinical-grade adenoviral vectors. Evidence of cirrhosis reversion. Gene Ther 2002, 9:127-134.
62. Xu G., Rockey D.C. Regulation of smooth muscle myosin heavy chain isoforms in hepatic myofibroblasts during liver injury. Hepatology 1999, 30:492A.
63. Pinzani M., Failli P., Ruocco C., et al. Fat-storing cells as liver-specific pericytes. Spatial dynamics of agonist-stimulated intracellular calcium transients. J Clin Invest 1992, 90:642-646.
64. Rockey D.C., Housset C.N., Friedman S.L. Activation-dependent contractility of rat hepatic lipocytes in culture and in vivo. J Clin Invest 1993, 92:1795-1804.
65. Iizuka M., Murata T., Hori M., et al. Increased contractility of hepatic stellate cells in cirrhosis is mediated by enhanced Ca2+-dependent and Ca2+-sensitization pathways. Am J Physiol Gastrointest Liver Physiol 2011, 300:G1010-G1021.
66. Xu H., Zhou Y., Lu C., et al. Salvianolic acid B lowers portal pressure in cirrhotic rats and attenuates contraction of rat hepatic stellate cells by inhibiting RhoA signaling pathway. Lab Invest 2012, 92:1738-1748.
67. Trebicka J., Hennenberg M., Schulze Pröbsting A., et al. Role of beta3-adrenoceptors for intrahepatic resistance and portal hypertension in liver cirrhosis. Hepatology 2009, 50:1924-1935.
68. Zou W.L., Yang Z., Zang Y.J., et al. Inhibitory effects of prostaglandin E1 on activation of hepatic stellate cells in rabbits with schistosomiasis. Hepatobiliary Pancreat Dis Int 2007, 6:176-181.
69. van Beuge M.M., Prakash J., Lacombe M., et al. Reduction of fibrogenesis by selective delivery of a Rho kinase inhibitor to hepatic stellate cells in mice. J Pharmacol Exp Ther 2011, 337:628-635.
70. Watanabe A., Sohail M.A., Gautam S., et al. Adenine induces differentiation of rat hepatic stellate cells. Dig Dis Sci 2012, 57:2371-2378.
71. Li J., Kuruba R., Wilson A., et al. Inhibition of endothelin-1-mediated contraction of hepatic stellate cells by FXR ligand. PLoS One 2010, 5:e13955.
72. Wright M.C., Issa R., Smart D.E., et al. Gliotoxin stimulates the apoptosis of human and rat hepatic stellate cells and enhances the resolution of liver fibrosis in rats. Gastroenterology 2001, 121:685-698.
73. Canbay A., Taimr P., Torok N., et al. Apoptotic body engulfment by a human stellate cell line is profibrogenic. Lab Invest 2003, 83:655-663.
74. Krizhanovsky V., Yon M., Dickins R.A., et al. Senescence of activated stellate cells limits liver fibrosis. Cell 2008, 134:657-667.
75. Deleve L.D., Wang X., Guo Y. Sinusoidal endothelial cells prevent rat stellate cell activation and promote reversion to quiescence. Hepatology 2008, 48:920-930.
76. Thoen L.F., Guimarães E.L., Grunsven L.A. Autophagy: a new player in hepatic stellate cell activation. Autophagy 2012, 8:126-128.
77. Thoen L.F., Guimarães E.L., Dollé L., et al. A role for autophagy during hepatic stellate cell activation. J Hepatol 2011, 55:1353-1360.
78. Herńndez-Gea V., Friedman S.L. Autophagy fuels tissue fibrogenesis. Autophagy 2012, 8:849-850.
79. Ramond M.J., Poynard T., Rueff B., et al. A randomized trial of prednisolone in patients with severe alcoholic hepatitis. N Engl J Med 1992, 326:507-512.
80. Spahr L., Rubbia-Brandt L., Pugin J., et al. Rapid changes in alcoholic hepatitis histology under steroids: correlation with soluble intercellular adhesion molecule-1 in hepatic venous blood. J Hepatol 2001, 35:582-589.
81. Powell L.W., Kerr J.F. Reversal of "cirrhosis" in idiopathic haemochromatosis following long-term intensive venesection therapy. Australas Ann Med 1970, 19:54-57.
82. Blumberg R.S., Chopra S., Ibrahim R., et al. Primary hepatocellular carcinoma in idiopathic hemochromatosis after reversal of cirrhosis. Gastroenterology 1988, 95:1399-1402.
83. Neuschwander-Tetri B.A., Brunt E.M., Wehmeier K.R., et al. Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone. Hepatology 2003, 38:1008-1017.
84. Rodríguez L., Cerbón-Ambriz J., Muñoz M.L. Effects of colchicine and colchiceine in a biochemical model of liver injury and fibrosis. Arch Med Res 1998, 29:109-116.
85. Kaplan M.M., Alling D.W., Zimmerman H.J., et al. A prospective trial of colchicine for primary biliary cirrhosis. N Engl J Med 1986, 315:1448-1454.
86. Kershenobich D., Vargas F., Garcia-Tsao G., et al. Colchicine in the treatment of cirrhosis of the liver. N Engl J Med 1988, 318:1709-1713.
87. Rambaldi A., Gluud C. Colchicine for alcoholic and non-alcoholic liver fibrosis or cirrhosis. Liver 2001, 21:129-136.
88. Morgan T.R., Weiss D.G., Nemchausky B., et al. Colchicine treatment of alcoholic cirrhosis: a randomized, placebo-controlled clinical trial of patient survival. Gastroenterology 2005, 128:882-890.
89. Rockey D.C., Maher J.J., Jarnagin W.R., et al. Inhibition of rat hepatic lipocyte activation in culture by interferon-gamma. Hepatology 1992, 16:776-784.
90. Muir A.J., Sylvestre P.B., Rockey D.C. Interferon gamma-1b for the treatment of fibrosis in chronic hepatitis C infection. J Viral Hepat 2006, 13:322-328.
91. Rockey D.C. Current and future anti-fibrotic therapies for chronic liver disease. Clin Liver Dis 2008, 12:939-962. xi.
92. Miyahara T., Schrum L., Rippe R., et al. Peroxisome proliferator-activated receptors and hepatic stellate cell activation. J Biol Chem 2000, 275:35715-35722.
93. Hazra S., Xiong S., Wang J., et al. Peroxisome proliferator-activated receptor gamma induces a phenotypic switch from activated to quiescent hepatic stellate cells. J Biol Chem 2004, 279:11392-11401.
94. Yang L., Chan C.C., Kwon O.S., et al. Regulation of peroxisome proliferator-activated receptor-gamma in liver fibrosis. Am J Physiol Gastrointest Liver Physiol 2006, 291:G902-G911.
95. Shafiei M.S., Shetty S., Scherer P.E., et al. Adiponectin regulation of stellate cell activation via PPARγ-dependent and -independent mechanisms. Am J Pathol 2011, 178:2690-2699.
96. Yang L., Stimpson S.A., Chen L., et al. Effectiveness of the PPARγ agonist, GW570, in liver fibrosis. Inflamm Res 2010, 59:1061-1071.
97. McHutchison J., Goodman Z., Patel K., et al. Farglitazar lacks antifibrotic activity in patients with chronic hepatitis C infection. Gastroenterology 2010, 138. 1365-1373e1-2.
98. Lieber C.S., Weiss D.G., Groszmann R., et al. Veterans Affairs Cooperative Study of polyenylphosphatidylcholine in alcoholic liver disease. Alcohol Clin Exp Res 2003, 27:1765-1772.
99. Boigk G., Stroedter L., Herbst H., et al. Silymarin retards collagen accumulation in early and advanced biliary fibrosis secondary to complete bile duct obliteration in rats. Hepatology 1997, 26:643-649.
100. Jia J.D., Bauer M., Cho J.J., et al. Antifibrotic effect of silymarin in rat secondary biliary fibrosis is mediated by downregulation of procollagen alpha1(I) and TIMP-1. J Hepatol 2001, 35:392-398.
101. Lieber C.S., Leo M.A., Cao Q., et al. Silymarin retards the progression of alcohol-induced hepatic fibrosis in baboons. J Clin Gastroenterol 2003, 37:336-339.
102. Ferenci P., Dragosics B., Dittrich H., et al. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol 1989, 9:105-113.
103. Parés A., Planas R., Torres M., et al. Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial. J Hepatol 1998, 28:615-621.
104. Nava-Ocampo A.A., Suster S., Muriel P. Effect of colchiceine and ursodeoxycholic acid on hepatocyte and erythrocyte membranes and liver histology in experimentally induced carbon tetrachloride cirrhosis in rats. Eur J Clin Invest 1997, 27:77-84.
105. Poupon R.E., Lindor K.D., Parés A., et al. Combined analysis of the effect of treatment with ursodeoxycholic acid on histologic progression in primary biliary cirrhosis. J Hepatol 2003, 39:12-16.
106. Lindor K.D., Kowdley K.V., Heathcote E.J., et al. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology 2004, 39:770-778.
107. Brown K.E., Poulos J.E., Li L., et al. Effect of vitamin E supplementation on hepatic fibrogenesis in chronic dietary iron overload. Am J Physiol 1997, 272:G116-G123.
108. Houglum K., Venkataramani A., Lyche K., et al. A pilot study of the effects of d-alpha-tocopherol on hepatic stellate cell activation in chronic hepatitis C. Gastroenterology 1997, 113:1069-1073.
109. Mezey E., Potter J.J., Rennie-Tankersley L., et al. A randomized placebo controlled trial of vitamin E for alcoholic hepatitis. J Hepatol 2004, 40:40-46.
110. Stewart S., Prince M., Bassendine M., et al. A trial of antioxidant therapy alone or with corticosteroids in acute alcoholic hepatitis. J Hepatol 2002, 36(Suppl):16.
111. Sanyal A.J., Chalasani N., Kowdley K.V., et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 2010, 362:1675-1685.
112. Sakaida I., Tsuchiya M., Kawaguchi K., et al. Herbal medicine Inchin-ko-to (TJ-135) prevents liver fibrosis and enzyme-altered lesions in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet. J Hepatol 2003, 38:762-769.
113. Shimizu I., Ma Y.R., Mizobuchi Y., et al. Effects of Sho-saiko-to, a Japanese herbal medicine, on hepatic fibrosis in rats. Hepatology 1999, 29:149-160.
114. Zhang X.L., Liu L., Jiang H.Q. Salvia miltiorrhiza monomer IH764-3 induces hepatic stellate cell apoptosis via caspase-3 activation. World J Gastroenterol 2002, 8:515-519.
115. Chen Z.X., Zhang S.J., Lao S.X., et al. He Jie Tang in the treatment of chronic hepatitis B patients. World J Gastroenterol 2005, 11:6638-6643.
116. Wang B.E. Treatment of chronic liver diseases with traditional Chinese medicine. J Gastroenterol Hepatol 2000, 15(Suppl):E67-E70.
117. Stedman C. Herbal hepatotoxicity. Semin Liver Dis 2002, 22:195-206.
118. Akriviadis E., Botla R., Briggs W., et al. Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: a double-blind, placebo-controlled trial. Gastroenterology 2000, 119:1637-1648.
119. Spahr L., Rubbia-Brandt L., Frossard J.L., et al. Combination of steroids with infliximab or placebo in severe alcoholic hepatitis: a randomized controlled pilot study. J Hepatol 2002, 37:448-455.
120. Tilg H., Jalan R., Kaser A., et al. Anti-tumor necrosis factor-alpha monoclonal antibody therapy in severe alcoholic hepatitis. J Hepatol 2003, 38:419-425.
121. Menon K.V., Stadheim L., Kamath P.S., et al. A pilot study of the safety and tolerability of etanercept in patients with alcoholic hepatitis. Am J Gastroenterol 2004, 99:255-260.
122. Naveau S., Chollet-Martin S., Dharancy S., et al. A double-blind randomized controlled trial of infliximab associated with prednisolone in acute alcoholic hepatitis. Hepatology 2004, 39:1390-1397.
123. Boetticher N.C., Peine C.J., Kwo P., et al. A randomized, double-blinded, placebo-controlled multicenter trial of etanercept in the treatment of alcoholic hepatitis. Gastroenterology 2008, 135:1953-1960.
124. Hernández E., Bucio L., Souza V., et al. Pentoxifylline downregulates alpha (I) collagen expression by the inhibition of IkappaBalpha degradation in liver stellate cells. Cell Biol Toxicol 2008, 24:303-314.
125. Zhang D., Jiang H., Wang Y., et al. Pentoxifylline inhibits hepatic stellate cells proliferation via the Raf/ERK pathway. APMIS 2012, 120:572-581.
126. Sidhu S.S., Goyal O., Singla M., et al. Pentoxifylline in severe alcoholic hepatitis: a prospective, randomised trial. J Assoc Physicians India 2012, 60:20-22.
127. Schaff Z., Lapis K., Szende B., et al. The effect of d-penicillamine on CCl4-induced experimental liver cirrhosis. Exp Pathol 1991, 43:111-120.
128. Lu S.C., Tsukamoto H., Mato J.M. Role of abnormal methionine metabolism in alcoholic liver injury. Alcohol 2002, 27:155-162.
129. Aithal G.P., Haugk B., Das S., et al. Monitoring methotrexate-induced hepatic fibrosis in patients with psoriasis: are serial liver biopsies justified?. Aliment Pharmacol Ther 2004, 19:391-399.
130. The results of a randomized double blind controlled trial evaluating malotilate in primary biliary cirrhosis. A European Multicentre Study Group. J Hepatol 1993, 17:227-235. Anonymous.
131. Bodenheimer H.C., Schaffner F., Sternlieb I., et al. A prospective clinical trial of D-penicillamine in the treatment of primary biliary cirrhosis. Hepatology 1985, 5:1139-1142.
132. Dickson E.R., Fleming T.R., Wiesner R.H., et al. Trial of penicillamine in advanced primary biliary cirrhosis. N Engl J Med 1985, 312:1011-1015.
133. Kaplan M.M., DeLellis R.A., Wolfe H.J. Sustained biochemical and histologic remission of primary biliary cirrhosis in response to medical treatment. Ann Intern Med 1997, 126:682-688.
134. Hendrickse M.T., Rigney E., Giaffer M.H., et al. Low-dose methotrexate is ineffective in primary biliary cirrhosis: long-term results of a placebo-controlled trial. Gastroenterology 1999, 117:400-407.
135. Bach N., Bodian C., Bodenheimer H., et al. Methotrexate therapy for primary biliary cirrhosis. Am J Gastroenterol 2003, 98:187-193.
136. Kaplan M.M., Cheng S., Price L.L., et al. A randomized controlled trial of colchicine plus ursodiol versus methotrexate plus ursodiol in primary biliary cirrhosis: ten-year results. Hepatology 2004, 39:915-923.
137. Mato J.M., Cámara J., Fernández de Paz J., et al. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol 1999, 30:1081-1089.
138. Rambaldi A., Gluud C. Meta-analysis of propylthiouracil for alcoholic liver disease-a Cochrane Hepato-Biliary Group Review. Liver 2001, 21:398-404.
139. Novobrantseva T.I., Akinc A., Borodovsky A., et al. Delivering silence: advancements in developing siRNA therapeutics. Curr Opin Drug Discov Devel 2008, 11:217-224.
140. Vaishnaw A.K., Gollob J., Gamba-Vitalo C., et al. A status report on RNAi therapeutics. Silence 2010, 1:14.
141. Bisht S., Khan M.A., Bekhit M., et al. A polymeric nanoparticle formulation of curcumin (NanoCurc™) ameliorates CCl4-induced hepatic injury and fibrosis through reduction of pro-inflammatory cytokines and stellate cell activation. Lab Invest 2011, 91:1383-1395.
142. Isaka Y., Brees D.K., Ikegaya K., et al. Gene therapy by skeletal muscle expression of decorin prevents fibrotic disease in rat kidney. Nat Med 1996, 2:418-423.
143. George J., Roulot D., Koteliansky V.E., et al. In vivo inhibition of rat stellate cell activation by soluble transforming growth factor beta type II receptor: a potential new therapy for hepatic fibrosis. Proc Natl Acad Sci U S A 1999, 96:12719-12724.
144. Gonzalo T., Beljaars L., van de Bovenkamp M., et al. Local inhibition of liver fibrosis by specific delivery of a platelet-derived growth factor kinase inhibitor to hepatic stellate cells. J Pharmacol Exp Ther 2007, 321:856-865.
145. Seki E., Schnabl B. Role of innate immunity and the microbiota in liver fibrosis: crosstalk between the liver and gut. J Physiol 2012, 590:447-458.
146. Gómez-Hurtado I., Santacruz A., Peiró G., et al. Gut microbiota dysbiosis is associated with inflammation and bacterial translocation in mice with CCl4-induced fibrosis. PLoS One 2011, 6:e23037.
147. Dapito D.H., Mencin A., Gwak G.Y., et al. Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4. Cancer Cell 2012, 21:504-516.
148. Seki E., De Minicis S., Osterreicher C.H., et al. TLR4 enhances TGF-beta signaling and hepatic fibrosis. Nat Med 2007, 13:1324-1332.
149. Fouts D.E., Torralba M., Nelson K.E., et al. Bacterial translocation and changes in the intestinal microbiome in mouse models of liver disease. J Hepatol 2012, 56:1283-1292.
150. Jiang X., Tsitsiou E., Herrick S.E., et al. MicroRNAs and the regulation of fibrosis. FEBS J 2010, 277:2015-2021.
151. Sekiya Y., Ogawa T., Yoshizato K., et al. Suppression of hepatic stellate cell activation by microRNA-29b. Biochem Biophys Res Commun 2011, 412:74-79.
152. Lakner A.M., Steuerwald N.M., Walling T.L., et al. Inhibitory effects of microRNA 19b in hepatic stellate cell-mediated fibrogenesis. Hepatology 2012, 56:300-310.
153. Barry-Hamilton V., Spangler R., Marshall D., et al. Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment. Nat Med 2010, 16:1009-1017.
154. López B., González A., Hermida N., et al. Role of lysyl oxidase in myocardial fibrosis: from basic science to clinical aspects. Am J Physiol Heart Circ Physiol 2010, 299:H1-H9.
155. Yamaguchi Y., Takihara T., Chambers R.A., et al. A peptide derived from endostatin ameliorates organ fibrosis. Sci Transl Med 2012, 4:136ra71.
156. Xu W., Hellerbrand C., Köhler U.A., et al. The Nrf2 transcription factor protects from toxin-induced liver injury and fibrosis. Lab Invest 2008, 88:1068-1078.
157. Kim I.H., Kim D.G., Hao P., et al. Anti-fibrotic effects of L-2-oxothiazolidine-4-carboxylic acid via modulation of nuclear factor erythroid 2-related factor 2 in rats. BMB Rep 2012, 45:348-353.
158. Zhao X.Y., Zeng X., Li X.M., et al. Pirfenidone inhibits carbon tetrachloride- and albumin complex-induced liver fibrosis in rodents by preventing activation of hepatic stellate cells. Clin Exp Pharmacol Physiol 2009, 36:963-968.
159. Titos E., Clària J., Planagumà A., et al. Inhibition of 5-lipoxygenase induces cell growth arrest and apoptosis in rat Kupffer cells: implications for liver fibrosis. FASEB J 2003, 17:1745-1747.
160. Rockey D.C., Caldwell S.H., Goodman Z.D., et al. Liver biopsy. Hepatology 2009, 49:1017-1044.
161. Pilette C., Rousselet M.C., Bedossa P., et al. Histopathological evaluation of liver fibrosis: quantitative image analysis vs semi-quantitative scores. Comparison with serum markers. J Hepatol 1998, 28:439-446.
162. O'Brien M.J., Keating N.M., Elderiny S., et al. An assessment of digital image analysis to measure fibrosis in liver biopsy specimens of patients with chronic hepatitis C. Am J Clin Pathol 2000, 114:712-718.
163. Bedossa P., Dargère D., Paradis V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology 2003, 38:1449-1457.
164. Regev A., Berho M., Jeffers L.J., et al. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gastroenterol 2002, 97:2614-2618.
165. Rockey D.C., Bissell D.M. Noninvasive measures of liver fibrosis. Hepatology 2006, 43:S113-S120.
166. Colli A., Fraquelli M., Andreoletti M., et al. Severe liver fibrosis or cirrhosis: accuracy of US for detection-analysis of 300 cases. Radiology 2003, 227:89-94.
167. Imbert-Bismut F., Ratziu V., Pieroni L., et al. Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet 2001, 357:1069-1075.
168. Wai C.T., Greenson J.K., Fontana R.J., et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 2003, 38:518-526.
169. Callewaert N., Van Vlierberghe H., Van Hecke A., et al. Noninvasive diagnosis of liver cirrhosis using DNA sequencer-based total serum protein glycomics. Nat Med 2004, 10:429-434.
170. Parkes J., Guha I.N., Roderick P., et al. Performance of serum marker panels for liver fibrosis in chronic hepatitis C. J Hepatol 2006, 44:462-474.
171. Mayo M.J., Parkes J., Adams-Huet B., et al. Prediction of clinical outcomes in primary biliary cirrhosis by serum enhanced liver fibrosis assay. Hepatology 2008, 48:1549-1557.
172. Parkes J., Roderick P., Harris S., et al. Enhanced liver fibrosis test can predict clinical outcomes in patients with chronic liver disease. Gut 2010, 59:1245-1251.
173. Li F., Song Z., Li Q., et al. Molecular imaging of hepatic stellate cell activity by visualization of hepatic integrin αvβ3 expression with SPECT in rat. Hepatology 2011, 54:1020-1030.
174. Wang Q.B., Han Y., Jiang T.T., et al. MR imaging of activated hepatic stellate cells in liver injured by CCl4 of rats with integrin-targeted ultrasmall superparamagnetic iron oxide. Eur Radiol 2011, 21:1016-1025.
175. Hagens W.I., Beljaars L., Mann D.A., et al. Cellular targeting of the apoptosis-inducing compound gliotoxin to fibrotic rat livers. J Pharmacol Exp Ther 2008, 324:902-910.
176. Park K., Hong S.W., Hur W., et al. Target specific systemic delivery of TGF-β siRNA/(PEI-SS)-g-HA complex for the treatment of liver cirrhosis. Biomaterials 2011, 32:4951-4958.
177. Poelstra K., Schuppan D. Targeted therapy of liver fibrosis/cirrhosis and its complications. J Hepatol 2011, 55:726-728.
178. Li Q., Yan Z., Li F., et al. The improving effects on hepatic fibrosis of interferon-γ liposomes targeted to hepatic stellate cells. Nanotechnology 2012, 23:265101.