Liver fibrosis is the excessive accumulation of extracellular matrix proteins including collagen that occurs in most types of chronic liver diseases. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and often requires liver transplantation. Our knowledge of the cellular and molecular mechanisms of liver fibrosis has greatly advanced. Activated hepatic stellate cells, portal fibroblasts, and myofibroblasts of bone marrow origin have been identified as major collagen-producing cells in the injured liver. These cells are activated by fibrogenic cytokines such as TGF-β1, angiotensin II, and leptin. Reversibility of advanced liver fibrosis in patients has been recently documented, which has stimulated researchers to develop antifibrotic drugs. Emerging antifibrotic therapies are aimed at inhibiting the accumulation of fibrogenic cells and/or preventing the deposition of extracellular matrix proteins. Although many therapeutic interventions are effective in experimental models of liver fibrosis, their efficacy and safety in humans is unknown. This review summarizes recent progress in the study of the pathogenesis and diagnosis of liver fibrosis and discusses current antifibrotic strategies.
Ramón Bataller, David A. Brenner
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Hedgehog signaling regulates epithelial mesenchymal transition during biliary fibrosis in rodents and humans
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Journal of Clinical Investigation | 2008 |
Angiotensin II-induced non-alcoholic fatty liver disease is mediated by oxidative stress in transgenic TG(mRen2)27(Ren2) rats
Y Wei, SE Clark, EM Morris, JP Thyfault, GM Uptergrove, AT Whaley-Connell, CM Ferrario, JR Sowers, JA Ibdah |
Journal of Hepatology | 2008 |
Redox mechanisms in hepatic chronic wound healing and fibrogenesis
E Novo, M Parola |
Fibrogenesis & Tissue Repair | 2008 |
Transforming growth factor-beta signaling in thoracic aortic aneurysm development: a paradox in pathogenesis
JA Jones, FG Spinale, JS Ikonomidis |
Journal of Vascular Research | 2008 |
Toll-like receptors, wound healing, and carcinogenesis
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Journal of Molecular Medicine | 2008 |
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GE Arteel |
Journal of Gastroenterology and Hepatology | 2008 |
Disruption of the Smad7 gene enhances CCI4-dependent liver damage and fibrogenesis in mice
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Journal of Cellular and Molecular Medicine | 2008 |
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JT Li, ZX Liao, J Ping, D Xu, H Wang |
Journal of Gastroenterology | 2008 |
Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver
SL Friedman |
Physiological reviews | 2008 |
Cellular Sources of Extracellular Matrix in Hepatic Fibrosis
RG Wells |
Clinics in Liver Disease | 2008 |
Fibrogenesis of parenchymal organs
T Kisseleva, DA Brenner |
Proceedings of the American Thoracic Society | 2008 |
Accumulation of Hedgehog-Responsive Progenitors Parallels Alcoholic Liver Disease Severity in Mice and Humans
Y Jung, KD Brown, RP Witek, A Omenetti, L Yang, M Vandongen, RJ Milton, IN Hines, RA Rippe, L Spahr, L Rubbia–Brandt, AM Diehl |
Gastroenterology | 2008 |
Recent advances in the pathogenesis and diagnosis of liver fibrosis
NJ Török |
Journal of Gastroenterology | 2008 |
Homocysteine enhances cell proliferation in hepatic myofibroblastic stellate cells
CG Zou, SY Gao, YS Zhao, SD Li, XZ Cao, Y Zhang, KQ Zhang |
Journal of Molecular Medicine | 2008 |
Death receptor 5 mediated-apoptosis contributes to cholestatic liver disease
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Proceedings of the National Academy of Sciences | 2008 |
Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity
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Genome biology | 2008 |
Immune Interactions in Hepatic Fibrosis
AP Holt, M Salmon, CD Buckley, DH Adams |
Clinics in Liver Disease | 2008 |
Experimental obstructive cholestasis: the wound-like inflammatory liver response
MA Aller, JL Arias, J García-Domínguez, JI Arias, M Durán, J Arias |
Fibrogenesis & Tissue Repair | 2008 |
Innate immunity and alcoholic liver fibrosis
WI Jeong, B Gao |
Journal of Gastroenterology and Hepatology | 2008 |
Liver cirrhosis
D Schuppan, NH Afdhal |
Lancet | 2008 |
Abrogation of the antifibrotic effects of natural killer cells/interferon-gamma contributes to alcohol acceleration of liver fibrosis
WI Jeong, O Park, B Gao |
Gastroenterology | 2008 |
Nuclear Cathepsin F Regulates Activation Markers in Rat Hepatic Stellate Cells
G Maubach, MC Lim, L Zhuo, WP Tansey |
Molecular biology of the cell | 2008 |
Specific siRNA Targeting the Receptor for Advanced Glycation End Products Inhibits Experimental Hepatic Fibrosis in Rats
Xia JR, Liu NF, Zhu NX |
International journal of molecular sciences | 2008 |
Activation of peroxisome proliferator-activated receptor-γ by curcumin blocks the signaling pathways for PDGF and EGF in hepatic stellate cells
J Lin, A Chen |
Laboratory Investigation | 2008 |
New cellular tools reveal complex epithelial-mesenchymal interactions in hepatocarcinogenesis
S Sagmeister, M Eisenbauer, C Pirker, T Mohr, K Holzmann, H Zwickl, C Bichler, D Kandioler, F Wrba, W Mikulits, C Gerner, M Shehata, O Majdic, B Streubel, W Berger, M Micksche, K Zatloukal, R Schulte-Hermann, B Grasl-Kraupp |
British Journal of Cancer | 2008 |
PTK787/ZK22258 attenuates stellate cell activation and hepatic fibrosis in vivo by inhibiting VEGF signaling
Y Liu, EL Lui, SL Friedman, L Li, T Ye, Y Chen, RT Poon, J Wo, TW Kok, ST Fan |
Laboratory Investigation | 2008 |
A red wine polyphenolic extract reduces the activation phenotype of cultured human liver myofibroblasts
V Neaud, J Rosenbaum |
World journal of gastroenterology : WJG | 2008 |
Nitric oxide promotes caspase-independent hepatic stellate cell apoptosis through the generation of reactive oxygen species
DA Langer, A Das, D Semela, N Kang-Decker, H Hendrickson, SF Bronk, ZS Katusic, GJ Gores, VH Shah |
Hepatology | 2008 |
Oxidized low-density-lipoprotein accumulation is associated with liver fibrosis in experimental cholestasis
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Clinics (São Paulo, Brazil) | 2008 |
Role of chemokines and their receptors in viral persistence and liver damage during chronic hepatitis C virus infection
JR Larrubia, S Benito-Martínez, M Calvino, E Sanz-de-Villalobos, T Parra-Cid |
World journal of gastroenterology : WJG | 2008 |
Recognition of Genetic Factors Influencing the Progression of Hepatitis C: Potential for Personalized Therapy
JR Jonsson, DM Purdie, AD Clouston, EE Powell |
Molecular diagnosis & therapy | 2008 |
TGF-beta and mesenchymal hepatic involvement after visceral leishmaniasis
MI Duarte, , CF Takamura, A Sesso, FF Tuon |
Parasitology Research | 2008 |
Effects of silymarin and pentoxifylline on matrix metalloproteinase-1 and -2 expression and apoptosis in experimental hepatic fibrosis.
Kara E, Coşkun T, Kaya Y, Yumuş O, Vatansever S, Var A |
Current Therapeutic Research | 2008 |
Inhibition of Integrin Alphavbeta6 on Cholangiocytes Blocks Tgfbeta Activation and Retards Biliary Fibrosis Progression
Patsenker E, Popov Y, Stickel F, Jonczyk A, Goodman SL, Schuppan D |
Gastroenterology | 2008 |
Nonalcoholic fatty liver disease: diagnosis and relation to metabolic syndrome and approach to treatment.
Lidofsky SD |
Current Diabetes Reports | 2008 |
Senescence of activated stellate cells limits liver fibrosis
Krizhanovsky V, Yon M, Dickins RA, Hearn S, Simon J, Miething C, Yee H, Zender L, Lowe SW |
Cell | 2008 |
Chronic Intermittent Hypoxia and Acetaminophen Induce Synergistic Liver Injury
Savransky V, Reinke C, Jun J, Bevans-Fonti S, Nanayakkara A, Li J, Myers AC, Torbenson MS, Polotsky VY |
Experimental Physiology | 2008 |
Effect of propranolol on the splanchnic and peripheral renin angiotensin system in cirrhotic patients
Vilas-Boas WW, Jr AR, da Cunha Ribeiro R, Vieira RL, Almeida J, Nadu AP, Silva AC, Santos RA |
World journal of gastroenterology : WJG | 2008 |
Therapy with bone marrow cells reduces liver alterations in mice chronically infected by Schistosoma mansoni
Oliveira SA, Souza BS, Guimarães-Ferreira CA, Barreto ES, Souza SC, Freitas LA, Ribeiro-dos-Santos R, Soares MB |
World journal of gastroenterology : WJG | 2008 |
Endothelial nitric oxide synthase is a critical factor in experimental liver fibrosis
Leung TM, Tipoe GL, Liong EC, Lau TY, Fung ML, Nanji AA |
International Journal of Experimental Pathology | 2008 |
TNFα is required for cholestasis-induced liver fibrosis in the mouse
Gäbele E, Froh M, Arteel GE, Uesugi T, Hellerbrand C, Schölmerich J, Brenner DA, Thurman RG, Rippe RA |
Biochemical and Biophysical Research Communications | 2008 |
Involvement of hepatic stimulator substance in experimentally induced fibrosis and cirrhosis in the rat.
Gribilas G, Zarros A, Zira A, Giaginis C, Tsourouflis G, Liapi C, Spiliopoulou C, Theocharis SE |
Digestive Diseases and Sciences | 2008 |
Protective effect of morin on dimethylnitrosamine-induced hepatic fibrosis in rats.
Lee HS, Jung KH, Park IS, Kwon SW, Lee DH, Hong SS |
Digestive Diseases and Sciences | 2008 |
Additive inhibitory effect of experimentally induced hepatic cirrhosis by agonists of peroxisome proliferator activator receptor gamma and retinoic acid receptor.
Bruck R, Weiss S, Aeed H, Pines M, Halpern Z, Zvibel I |
Digestive Diseases and Sciences | 2008 |