Emerging therapies for liver fibrosis

Digestive Diseases

Volumn 24, Issue 1-2, 2006, Pages 174-183

  Fowell, Andrew J ^a   Iredale, John P ^b  

^a UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^b UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

Antifibrotic therapy; Apoptosis; Cirrhosis; Hepatic stellate cell; Matrix degradation

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ALPHA TOCOPHEROL; ANTIOXIDANT; CAMOSTAT; CANDESARTAN; CAPTOPRIL; CARIPORIDE; COLCHICINE; CORTICOSTEROID; FUMAGILLOL CHLOROACETYLCARBAMATE; GLYCYRRHIZIC ACID; INFLIXIMAB; INTERFERON; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; MALOTILATE; PEGINTERFERON; PENTOXIFYLLINE; PHOSPHATIDYLCHOLINE; PHOSPHODIESTERASE INHIBITOR; PROTEIN TYROSINE KINASE INHIBITOR; RECOMBINANT INTERLEUKIN 10; RESVERATROL; RETINOL PALMITATE; RIBAVIRIN; S ADENOSYLMETHIONINE; SILYBUM MARIANUM EXTRACT; THALIDOMIDE; TRICHOSTATIN A; UNINDEXED DRUG; URSODEOXYCHOLIC ACID;

APOPTOSIS; AUTOIMMUNE DISEASE; CLINICAL TRIAL; DISEASE MODEL; DRUG EFFECT; DRUG EFFICACY; DRUG RESPONSE; EXTRACELLULAR MATRIX; FIBROGENESIS; HEPATITIS; HUMAN; LIVER CELL; LIVER CIRRHOSIS; LIVER DYSFUNCTION; LIVER FIBROSIS; LIVER INJURY; NONHUMAN; PATHOPHYSIOLOGY; PORTAL HYPERTENSION; PRIORITY JOURNAL; REVIEW; SEPSIS; STELLATE CELL; VIRUS HEPATITIS;

ANIMALS; ANTI-INFLAMMATORY AGENTS; ANTIOXIDANTS; APOPTOSIS; HUMANS; LIVER CIRRHOSIS; PROTECTIVE AGENTS; TREATMENT OUTCOME;

EID: 33646745744     PISSN: 02572753     EISSN: None     Source Type: Journal    
DOI: 10.1159/000090320     Document Type: Review

References (72)

1. Department of Health: Annual Report of the Chief Medical Officer (2001).
2. Maher JJ: Interactions between hepatic stellate cells and the immune system. Semin Liver Dis 2001;21:417-426.
3. Friedman SL: Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem 2000;275:2247-2250.
4. Iredale JP, Murphy G, Hembry RM, Friedman SL, Arthur MJ: Human hepatic lipocytes synthesize tissue inhibitor of metalloproteinases-1: implications for regulation of matrix degradation in liver. J Clin Invest 1992;90:282-287.
5. Schuppan D, Ruehl M, Somasundaram R, Hahn EG: Matrix as a modulator of hepatic fibrogenesis. Semin Liver Dis 2001;21:351-372.
6. Rockey DC: Hepatic blood flow regulation by stellate cells in normal and injured liver. Semin Liver Dis 2001;21:337-349.
7. Poynard T, McHutchison J, Manns M, Trepo C, Lindsay K, Goodman Z, Ling MH, Albrecht J: Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology 2002;122:1303-1313.
8. Issa R, Zhou X, Constandinou CM, Fallowfield J, Millward-Sadler H, Gaca MDA, Sands E, Suliman I, Trim N, Knorr A, Arthur MJP, Benyon RC, Iredale JP: Spontaneous recovery from micronodular cirrhosis: evidence for incomplete resolution associated with matrix cross-linking. Gastroenterology 2004;126:1795-1808.
9. Iredale JP, Benyon RC, Pickering J, McCullen M, Northrop M, Pawley S, Hovell C, Arthur MJ: 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.
10. Benyon RC, Arthur MJP: Extracellular matrix degradation and the role of hepatic stellate cells. Semin Liver Dis 2001;21:373-384.
11. Wright MC, Issa R, Smart DE, Trim N, Murray GI, Primrose JN, Arthur MJ, Iredale JP, Mann DA: 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.
12. Grant A, Neuberger J: Guidelines on the use of liver biopsy in clinical practice. Gut 1999;45(suppl 4):IV1-IV11.
13. Imbert-Bismut F, Ratziu V, Pieroni L, Charlotte F, Benhamou Y, Poynard T; MULTIVIRC Group: Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet 2001;357:1069-1075.
14. Rossi E, Adams L, Prins A, Bulsara M, de Boer B, Garas G, MacQuillan G, Speers D, Jeffrey G: Validation of the FibroTest biochemical markers score in assessing liver fibrosis in hepatitis C patients. Clin Chem 2003;49:450-454.
15. Iredale JP: Hepatic stellate cell behavior during resolution of liver injury. Semin Liver Dis 2001;21:427-436.
16. Kershenobich D, Vargas F, Garcia-Tsao G, Perez Tamayo R, Gent M, Rojkind M: Colchicine in the treatment of cirrhosis of the liver. N Engl J Med 1988;318:1709-1713.
17. Rambaldi A, Gluud C: Colchicine for alcoholic and non-alcoholic liver fibrosis and cirrhosis. Cochrane Database Syst Rev 2001;3:CD002148.
18. Ryhanen L, Stenback F, Ala-Kokko L, Savolainen ER: The effect of malotilate on type III and type IV collagen, laminin and fibronectin metabolism in dimethylnitrosamine-induced liver fibrosis in the rat. J Hepatol 1996;24:238-245.
19. Keiding S, Badsberg JH, Becker U, Bentsen KD, Bonnevie O, Caballeria J, Eriksen J, Hardt F, Keiding N, Morgan M, et al: The prognosis of patients with alcoholic liver disease. An international randomized, placebo-controlled trial on the effect of malotilate on survival. J Hepatol 1994;20:454-460.
20. Maher JJ: Treatment of alcoholic hepatitis. J Gastroenterol Hepatol 2002;17:448-455.
21. Mitchison HC, Palmer JM, Bassendine MF, Watson AJ, Record CO, James OF: A controlled trial of prednisolone treatment in primary biliary cirrhosis: three-year results. J Hepatol 1992;15:336-344.
22. Bruck R, Shirin H, Hershkoviz R, Lider O, Kenet G, Aeed H, Matas Z, Zaidel L, Halpern Z: Analysis of Arg-Gly-Asp mimetics and soluble receptor of tumour necrosis factor as therapeutic modalities for concanavalin A induced hepatitis in mice. Gut 1997;40:133-138.
23. Tilg H, Jalan R, Kaser A, Davies NA, Offner FA, Hodges SJ, Ludwiczek O, Shawcross D, Zoller H, Alisa A, Mookerjee RP, Graziadei I, Datz C, Trauner M, Schuppan D, Obrist P, Vogel W, Williams R: Anti-tumor necrosis factor-alpha monoclonal antibody therapy in severe alcoholic hepatitis. J Hepatol 2003;38:419-425.
24. Muriel P, Fernandez-Martinez E, Perez-Alvarez V, Lara-Ochoa F, Ponce S, Garcia J, Shibayama M, Tsutsumi V: Thalidomide ameliorates carbon tetrachloride induced cirrhosis in the rat. Eur J Gastroenterol Hepatol 2003;15:951-957.
25. Harada H, Wakabayashi G, Takayanagi A, Shimazu M, Matsumoto K, Obara H, Shimizu N, Kitajima M: Transfer of the interleukin-1 receptor antagonist gene into rat liver abrogates hepatic ischemia-reperfusion injury. Transplantation 2002;74:1434-1441.
26. Thompson K, Maltby J, Fallowfield J, McAulay M, Millward-Sadler H, Sheron N: Interleukin-10 expression and function in experimental murine liver inflammation and fibrosis. Hepatology 1998;28:1597-1606.
27. Thompson KC, Trowern A, Fowell A, Marathe M, Haycock C, Arthur MJ, Sheron N: Primary rat and mouse hepatic stellate cells express the macrophage inhibitor cytokine interleukin-10 during the course of activation In vitro. Hepatology 1998;28:1518-1524.
28. Nelson DR, Tu Z, Soldevila-Pico C, Abdelmalek M, Zhu H, Xu YL, Cabrera R, Liu C, Davis GL: Long-term interleukin 10 therapy in chronic hepatitis C patients has a proviral and anti-inflammatory effect. Hepatology 2003;38:859-868.
29. Suzuki K, Aoki K, Ohnami S, Yoshida K, Kazui T, Kato N, Inoue K, Kohara M, Yoshida T: Adenovirus-mediated gene transfer of interferon alpha inhibits hepatitis C virus replication in hepatocytes. Biochem Biophys Res Commun 2003;307:814-819.
30. Naziroglu M, Cay M, Ustundag B, Aksakal M, Yekeler H: Protective effects of vitamin E on carbon tetrachloride-induced liver damage in rats. Cell Biochem Funct 1999;17:253-259.
31. Houglum K, Venkataramani A, Lyche K, Chojkier M: A pilot study of the effects of d-alpha-tocopherol on hepatic stellate cell activation in chronic hepatitis C. Gastroenterology 1997;113:1069-1073.
32. Pares A, Planas R, Torres M, Caballeria J, Viver JM, Acero D, Panes J, Rigau J, Santos J, Rodes J: 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.
33. Mato JM, Camara J, Fernandez de Paz J, Caballeria L, Coll S, Caballero A, Garcia-Buey L, Beltran J, Benita V, Caballeria J, Sola R, Moreno-Otero R, Barrao F, Martin-Duce A, Correa JA, Pares A, Barrao E, Garcia-Magaz I, Puerta JL, Moreno J, Boissard G, Ortiz P, Rodes J: S-adenosylmethionine in alcoholic liver cirrhosis: A randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol 1999;30:1081-1089.
34. Baroni GS, D'Ambrosio L, Curto P, Casini A, Mancini R, Jezequel AM, Benedetti A: Interferon gamma decreases hepatic stellate cell activation and extracellular matrix deposition in rat liver fibrosis. Hepatology 1996;23:1189-1199.
35. Niki T, Pekny M, Hellemans K, Bleser PD, Berg KV, Vaeyens F, Quartier E, Schuit F, Geerts A: A histone deacetylase inhibitor, trichostatin A, suppresses myofibroblastic differentiation of rat hepatic stellate cells in primary culture. Hepatology 1999;29:858-867.
36. Jeong HG, You HJ, Park SJ, Moon AR, Chung YC, Kang SK, Chun HK: Hepatoprotective effects of 18beta-glycyrrhetinic acid on carbon tetrachloride-induced liver injury: inhibition of cytochrome P450 2E1 expression. Pharmacol Res 2002;46:221-227.
37. Mizobuchi Y, Shimizu I, Yasuda M, Hori H, Shono M, Ito S: Retinyl palmitate reduces hepatic fibrosis in rats induced by dimethylnitrosamine or pig serum. J Hepatol 1998;29:933-943.
38. Stickel F, Brinkhaus B, Krahmer N, Seitz HK, Hahn EG, Schuppan D: Antifibrotic properties of botanicals in chronic liver disease. Hepatogastroenterology 2002;49:1102-1108.
39. Pinzani M, Marra F, Caligiuri A, DeFranco R, Gentilini A, Failli P, Gentilini P: Inhibition by pentoxifylline of extracellular signal-regulated kinase activation by platelet-derived growth factor in hepatic stellate cells. Br J Pharmacol 1996;119:1117-1124.
40. + exchange inhibition by cariporide reduces liver fibrosis in the rat. Hepatology 2003;37:256-266.
41. Reif S, Weis B, Aeed H, Gana-Weis M, Zaidel L, Avni Y, Romanelli RG, Pinzani M, Kloog Y, Bruck R: The Ras antagonist, farnesylthiosalicylic acid (FTS), inhibits experimentally-induced liver cirrhosis in rats. J Hepatol 1999;31:1053-1061.
42. Wang YQ, Ikeda K, Ikebe T, Hirakawa K, Sowa M, Nakatani K, Kawada N, Kaneda K: Inhibition of hepatic stellate cell proliferation and activation by the semisynthetic analogue of fumagillin TNP-470 in rats. Hepatology 2000;32:980-989.
43. Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, Joensuu H: Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002;347:472-480.
44. Okuno M, Akita K, Moriwaki H, Kawada N, Ikeda K, Kaneda K, Suzuki Y, Kojima S: Prevention of rat hepatic fibrosis by the protease inhibitor, camostat mesilate, via reduced generation of active TGF-beta. Gastroenterology 2001;120:1784-1800.
45. George J, Roulot D, Koteliansky VE, Bissell DM: 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 USA 1999;96:12719-12724.
46. Qi Z, Atsuchi N, Ooshima A, Takeshita A, Ueno H: Blockade of type beta transforming growth factor signaling prevents liver fibrosis and dysfunction in the rat. Proc Natl Acad Sci USA 1999;96:2345-2349.
47. Arias M, Sauer-Lehnen S, Treptau J, Janoschek N, Theuerkauf I, Buettner R, Gressner AM, Weiskirchen R: Adenoviral expression of a transforming growth factor-beta1 antisense mRNA is effective in preventing liver fibrosis in bile-duct ligated rats. BMC Gastroenterol 2003;3:29.
48. Dooley S, Hamzavi J, Breitkopf K, Wiercinska E, Said HM, Lorenzen J, Ten Dijke P, Gressner AM: Smad7 prevents activation of hepatic stellate cells and liver fibrosis in rats. Gastroenterology 2003;125:178-191.
49. Ueki T, Kaneda Y, Tsutsui H, Nakanishi K, Sawa Y, Morishita R, Matsumoto K, Nakamura T, Takahashi H, Okamoto E, Fujimoto J: Hepatocyte growth factor gene therapy of liver cirrhosis in rats. Nat Med 1999;5:226-230.
50. Marra F, Efsen E, Romanelli RG, Caligiuri A, Pastacaldi S, Batignani G, Bonacchi A, Caporale R, Laffi G, Pinzani M, Gentilini P: Ligands of peroxisome proliferator-activated receptor gamma modulate profibrogenic and proinflammatory actions in hepatic stellate cells. Gastroenterology 2000;119:466-478.
51. Matsusaka T, Katori H, Inagami T, Fogo A, Ichikawa I: Communication between myocytes and fibroblasts in cardiac remodeling in angiotensin chimeric mice. J Clin Invest 1999;103:1451-1458.
52. Klahr S, Morrissey JJ: The role of vasoactive compounds, growth factors and cytokines in the progression of renal disease. Kidney Int Suppl 2000;75:S7-S14.
53. Jonsson JR, Clouston AD, Ando Y, Kelemen LI, Horn MJ, Adamson MD, Purdie DM, Powell EE: Angiotensin-converting enzyme inhibition attenuates the progression of rat hepatic fibrosis. Gastroenterology 2001;121:148-155.
54. Yoshiji H, Kuriyama S, Yoshii J, Ikenaka Y, Noguchi R, Nakatani T, Tsujinoue H, Fukui H: Angiotensin-II type 1 receptor interaction is a major regulator for liver fibrosis development in rats. Hepatology 2001;34:745-750.
55. Rockey DC, Weisiger RA: Endothelin induced contractility of stellate cells from normal and cirrhotic rat liver: Implications for regulation of portal pressure and resistance. Hepatology 1996;24:233-240.
56. Yu Q, Shao R, Qian HS, George SE, Rockey DC: Gene transfer of the neuronal NO synthase isoform to cirrhotic rat liver ameliorates portal hypertension. J Clin Invest 2000;105:741-748.
57. Rockey DC, Chung JJ: Endothelin antagonism in experimental hepatic fibrosis. Implications for endothelin in the pathogenesis of wound healing. J Clin Invest 1996;98:1381-1388.
58. Iimuro Y, Nishio T, Morimoto T, Nitta T, Stefanovic B, Choi SK, Brenner DA, Yamaoka Y: Delivery of matrix metalloproteinase-1attenuates established liver fibrosis in the rat. Gastroenterology 2003;24:445-458.
59. Parsons CJ, Bradford BU, Pan CQ, Cheung E, Schauer M, Knorr A, Krebs B, Kraft S, Zahn S, Brocks B, Feirt N, Mei B, Cho MS, Ramamoorthi R, Roldan G, Ng P, Lum P, Hirth-Dietrich C, Tomkinson A, Brenner DA: Antifibrotic effects of a tissue inhibitor of metalloproteinase-1antibody on established liver fibrosis in rats. Hepatology 2004;40:1106-1115.
60. Williams EJ, Benyon RC, Trim N, Hadwin R, Grove BH, Arthur MJ, Unemori EN, Iredale JP: Relaxin inhibits effective collagen deposition by cultured hepatic stellate cells and decreases rat liver fibrosis in vivo. Gut 2001;49:577-583.
61. Salgado S, Garcia J, Vera J, Siller F, Bueno M, Miranda A, Segura A, Grijalva G, Segura J, Orozco H, Hernandez-Pando R, Fafutis M, Aguilar LK, Aguilar-Cordova E, Armendariz-Borunda J: Liver cirrhosis is reverted by urokinase-type plasminogen activator gene therapy. Mol Ther 2000;2:545-551.
62. Gimenez A, Pares A, Alie S, Camps J, Deulofeu R, Caballeria J, Rodes J: Fibrogenic and collagenolytic activity in carbon-tetrachloride-injured rats: Beneficial effects of zinc administration. J Hepatol 1994;21:292-298.
63. Saile B, Knittel T, Matthes N, Schott P, Ramadori G: CD95/CD95L-mediated apoptosis of the hepatic stellate cell: a mechanism terminating uncontrolled hepatic stellate cell proliferation during hepatic tissue repair. Am J Pathol 1997;151:1265-1272.
64. Oakley F, Trim N, Constandinou CM, Ye W, Gray AM, Frantz G, Hillan K, Kendall T, Benyon RC, Mann DA, Iredale JP: Hepatocytes express nerve growth factor during liver injury: evidence for paracrine regulation of hepatic stellate cell apoptosis. Am J Pathol 2003;163:1849-1858.
65. Fischer R, Schmitt M, Bode JG, Haussinger D: Expression of the peripheral-type benzodiazepine receptor and apoptosis induction in hepatic stellate cells. Gastroenterology 2001;120:1212-1226.
66. Li L, Tao J, Davaille J, Feral C, Mallat A, Rieusset J, Vidal H, Lotersztajn S: 15-deoxy-Delta 12,14-prostaglandin J2 induces apoptosis of human hepatic myofibroblasts: a pathway involving oxidative stress independently of peroxisome-proliferator-activated receptors. J Biol Chem 2001;276:38152-38158.
67. Iwamoto H, Sakai H, Tada S, Nakamuta M, Nawata H: Induction of apoptosis in rat hepatic stellate cells by disruption of integrin-mediated cell adhesion. J Lab Clin Med 1999;134:83-89.
68. Abriss B, Hollweg G, Gressner AM, Weiskirchen R: Adenoviral-mediated transfer of p53 or retinoblastoma protein blocks cell proliferation and induces apoptosis in culture-activated hepatic stellate cells. J Hepatol 2003;38:169-178.
69. Oakley F, Mann J, Ruddell RG, Pickford J, Weinmaster G, Mann DA: Basal expression of IkappaBalpha is controlled by the mammalian transcriptional repressor RBP-J (CBF1) and its activator Notch1. J Biol Chem 2003;278:24359-24370.
70. Oakley F, Meso M, Iredale JP, Green K, Marek CJ, Zhou X, May MJ, Millward-Sadler H, Wright MC, Mann DA: Inhibition of inhibitor of kappaB kinases stimulates hepatic stellate cell apoptosis and accelerated recovery from rat liver fibrosis. Gastroenterology 2005;128:108-120.
71. Beljaars L, Molema G, Weert B, Bonnema H, Olinga P, Groothuis GM, Meijer DK, Poelstra K: Albumin modified with mannose 6-phosphate: A potential carrier for selective delivery of antifibrotic drugs to rat and human hepatic stellate cells. Hepatology 1999;29:1486-1493.
72. Beljaars L, Molema G, Schuppan D, Geerts A, De Bleser PJ, Weert B, Meijer DK, Poelstra K: Successful targeting to rat hepatic stellate cells using albumin modified with cyclic peptides that recognize the collagen type VI receptor. J Biol Chem 2000;275:12743-12751.