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
Title and authors | Publication | Year |
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CCR1 and CCR5 Promote Hepatic Fibrosis
Ekihiro Seki , Samuele De Minicis, Johannes Kluwe, Sayaka Inokuchi, Geum-Youn Gwak, Christina A. Bursill, Josep M. Llovet, David A. Brenner and Robert F. Schwabe |
Journal of Clinical Investigation | 2009 |
In liver fibrosis, dendritic cells govern hepatic inflammation by acquiring enhanced capacity to engage innate and adaptive immunity via TNF-alpha
Michael Connolly, Andrea Bedrosian, Jon Mallen-St. Clair, Aaron Mitchell, Junaid Ibrahim, Andrea Stroud, H. Leon Pachter, Dafna Bar-Sagi, Alan Frey, George Miller |
Journal of Clinical Investigation | 2009 |
Hedgehog-mediated epithelial-to-mesenchymal transition and fibrogenic repair in nonalcoholic fatty liver disease
WK Syn, Y Jung, A Omenetti, M Abdelmalek, CD Guy, L Yang, J Wang, RP Witek, CM Fearing, TA Pereira, V Teaberry, SS Choi, J Conde-Vancells, GF Karaca, AM Diehl |
Gastroenterology | 2009 |
Peroxidasin is secreted and incorporated into the extracellular matrix of myofibroblasts and fibrotic kidney
Z Péterfi, A Donkó, A Orient, A Sum, A Prókai, B Molnár, Z Veréb, E Rajnavölgyi, KJ Kovács, V Müller, AJ Szabó, M Geiszt |
The American Journal of Pathology | 2009 |
Cathepsins B and D drive hepatic stellate cell proliferation and promote their fibrogenic potential
A Moles, N Tarrats, JC Fernández-Checa, M Marí |
Hepatology | 2009 |
Antifibrotic effects of CXCL9 and its receptor CXCR3 in livers of mice and humans
HE Wasmuth, F Lammert, MM Zaldivar, R Weiskirchen, C Hellerbrand, D Scholten, ML Berres, H Zimmermann, KL Streetz, F Tacke, S Hillebrandt, P Schmitz, H Keppeler, T Berg, E Dahl, N Gassler, SL Friedman, C Trautwein |
Gastroenterology | 2009 |
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd |
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology | 2009 |
Toll-like receptors as targets in chronic liver diseases
A Mencin, J Kluwe, RF Schwabe |
Gut | 2009 |
AMP-activated protein kinase in the regulation of hepatic energy metabolism: from physiology to therapeutic perspectives
B Viollet, B Guigas, J Leclerc, S Hébrard, L Lantier, R Mounier, F Andreelli, M Foretz |
Acta physiologica (Oxford, England) | 2009 |
Role of the receptor for advanced glycation end products in hepatic fibrosis
C Lohwasser, D Neureiter, Y Popov, M Bauer, D Schuppan |
World journal of gastroenterology : WJG | 2009 |
Disruption of TAK1 in hepatocytes causes hepatic injury, inflammation, fibrosis, and carcinogenesis
S Inokuchi, T Aoyama, K Miura, CH Osterreicher, Y Kodama, K Miyai, S Akira, DA Brenner, E Seki |
Proceedings of the National Academy of Sciences | 2009 |
Liver natural killer and natural killer T cells: immunobiology and emerging roles in liver diseases
B Gao, S Radaeva, O Park |
Journal of leukocyte biology | 2009 |
CCR2 promotes hepatic fibrosis in mice
E Seki, S Minicis, S Inokuchi, K Taura, K Miyai, N Rooijen, RF Schwabe, DA Brenner |
Hepatology | 2009 |
Protection against hepatocyte mitochondrial dysfunction delays fibrosis progression in mice
C Mitchell, MA Robin, A Mayeuf, M Mahrouf-Yorgov, A Mansouri, M Hamard, D Couton, B Fromenty, H Gilgenkrantz |
The American Journal of Pathology | 2009 |
Pharmacological inhibition of integrin alphavbeta3 aggravates experimental liver fibrosis and suppresses hepatic angiogenesis
E Patsenker, Y Popov, F Stickel, V Schneider, M Ledermann, H Sägesser, G Niedobitek, SL Goodman, D Schuppan |
Hepatology | 2009 |
Dual Role of CCR2 in the Constitution and the Resolution of Liver Fibrosis in Mice
C Mitchell, D Couton, JP Couty, M Anson, AM Crain, V Bizet, L Rénia, S Pol, V Mallet, H Gilgenkrantz |
The American Journal of Pathology | 2009 |
Curcumin eliminates oxidized LDL roles in activating hepatic stellate cells by suppressing gene expression of lectin-like oxidized LDL receptor-1
Q Kang, A Chen |
Laboratory Investigation | 2009 |
Diverse roles of invariant natural killer T cells in liver injury and fibrosis induced by carbon tetrachloride
O Park, WI Jeong, L Wang, H Wang, ZX Lian, ME Gershwin, B Gao |
Hepatology | 2009 |
Hepatic wound repair
M Parola, M Pinzani |
Fibrogenesis & Tissue Repair | 2009 |
Hepatic Stellate Cell-Specific Gene Silencing Induced by an Artificial MicroRNA for Antifibrosis In Vitro
Y Chang, H Jiang, X Sun, X Cai, X He, P Li, W Tang, Y Song, J Lin |
Digestive Diseases and Sciences | 2009 |
Histone deacetylase inhibition and the regulation of cell growth with particular reference to liver pathobiology
F Joanna, V Mathieu, S Sarah, D Sarah, V Karin, V Tamara, R Vera |
Journal of Cellular and Molecular Medicine | 2009 |
Role of host genetics in fibrosis
GL Hold, P Untiveros, KA Saunders, EM El-Omar |
Fibrogenesis & Tissue Repair | 2009 |
Insulin-like growth factor binding protein-7 induces activation and transdifferentiation of hepatic stellate cells in vitro
LX Liu, S Huang, QQ Zhang, Y Liu, DM Zhang, XH Guo, DW Han |
World journal of gastroenterology : WJG | 2009 |
Evaluation of intracellular signalling pathways in response to insulin-like growth factor I in apoptotic-resistant activated human hepatic stellate cells
A Gentilini, B Lottini, M Brogi, A Caligiuri, L Cosmi, F Marra, M Pinzani |
Fibrogenesis & Tissue Repair | 2009 |
Alterations of Bone Marrow Sinusoidal Endothelium in Rat and Patients with Liver Cirrhosis
S Zhao, YM Fu, XF Li, ZF Jin, RB Zhao, Q Huang, FM Zhang, WH Zhang |
Digestive Diseases and Sciences | 2009 |
Kupffer cells mediate leptin-induced liver fibrosis
J Wang, I Leclercq, JM Brymora, N Xu, M Ramezani-Moghadam, RM London, D Brigstock, J George |
Gastroenterology | 2009 |
Renin-angiotensin system in the pathogenesis of liver fibrosis
RM Pereira, RA Santos, FL da Dias, MM Teixeira, AC Silva |
World journal of gastroenterology : WJG | 2009 |
Antifibrotic effects of green tea on in vitro and in vivo models of liver fibrosis
HK Kim, TH Yang, HY Cho |
World journal of gastroenterology : WJG | 2009 |
Retinoic Acid-mediated Nuclear Receptor Activation and Hepatocyte Proliferation
N Bushue, YJ Wan |
Journal of Experimental & Clinical Medicine | 2009 |
Molecular mechanisms underlying hepatocellular carcinoma.
Merle P, Trepo C |
Viruses | 2009 |
Chinese medicinal herbs in treating model rats with hepatic fibrosis.
Zhou YX, Chen J, Li JP, Wang YL, Jin XD |
African journal of traditional, complementary, and alternative medicines : AJTCAM | 2009 |
Implications of Cellular Senescence in Tissue Damage Response, Tumor Suppression, and Stem Cell Biology
Krizhanovsky V, Xue W, Zender L, Yon M, Hernando E, Lowe SW |
Cold Spring Harbor Symposia on Quantitative Biology | 2009 |
Multiple variants in toll-like receptor 4 gene modulate risk of liver fibrosis in Caucasians with chronic hepatitis C infection
Yonghong L, Chang M, Abar O, Garcia V, Rowland C, Catanese J, Ross D, Broder S, Shiffman M, Cheung R, Wright T, Friedman SL, Sninsky J |
Journal of Hepatology | 2009 |
CD38-mediated Ca2+ Signaling Contributes to Angiotensin II-induced Activation of Hepatic Stellate Cells: ATTENUATION OF HEPATIC FIBROSIS BY CD38 ABLATION
Kim SY, Cho BH, Kim UH |
The Journal of biological chemistry | 2009 |
Emerging role of microRNAs in liver diseases
Bala S, Marcos M, Szabo G |
World journal of gastroenterology : WJG | 2009 |
Involvement of Sphingosine 1-Phosphate (SIP)/S1P3 Signaling in Cholestasis-Induced Liver Fibrosis
Li C, Jiang X, Yang L, Liu X, Yue S, Li L |
The American Journal of Pathology | 2009 |
TGF-β1 Gene Silencing for Treating Liver Fibrosis
Cheng K, Yang N, Mahato RI |
Molecular Pharmaceutics | 2009 |
Effect of Fuzheng Huayu formula and its actions against liver fibrosis
Liu C, Hu Y, Xu L, Liu C, Liu P |
Chinese medicine | 2009 |
Liver and spleen volume variations in patients with hepatic fibrosis
Liu P, Li P, He W, Zhao LQ |
World journal of gastroenterology : WJG | 2009 |
Novel Serum Markers of Fibrosis Progression for the Follow-Up of Hepatitis C Virus-Infected Patients
Caillot F, Hiron M, Goria O, Gueudin M, Francois A, Scotte M, Daveau M, Salier JP |
The American Journal of Pathology | 2009 |
Insoluble, Speckled Cytosolic Distribution of Retinoic Acid Receptor Alpha Protein as a Marker of Hepatic Stellate Cell Activation In Vitro
Mezaki Y, Yamaguchi N, Yoshikawa K, Miura M, Imai K, Itoh H, Senoo H |
Journal of Histochemistry & Cytochemistry | 2009 |
Up-regulation of uPARAP/Endo180 during culture activation of rat hepatic stellate cells and its presence in hepatic stellate cell lines from different species
Mousavi SA, Fønhus MS, Berg T |
BMC cell biology | 2009 |
Relationship between angiotensin-(1-7) and angiotensin II correlates with hemodynamic changes in human liver cirrhosis
Vilas-Boas WW, Ribeiro-Oliveira Jr A, Pereira RM, da Cunha Ribeiro R, Almeida J, Nadu AP, Simões e Silva AC, dos Santos RA |
World journal of gastroenterology : WJG | 2009 |
Angiotensin-receptor blockers as therapy for mild-to-moderate hypertension-associated non-alcoholic steatohepatitis
Georgescu EF, Ionescu R, Niculescu M, Mogoanta L, Vancica L |
World journal of gastroenterology : WJG | 2009 |
HCV Induces Oxidative and ER Stress, and Sensitizes Infected Cells to Apoptosis in SCID/Alb-uPA Mice
Joyce MA, Walters KA, Lamb SE, Yeh MM, Zhu LF, Kneteman N, Doyle JS, Katze MG, Tyrrell DL |
PLoS pathogens | 2009 |
TNF-α plays a role in hepatocyte apoptosis in Niemann-Pick type C liver disease
Rimkunas VM, Graham MJ, Crooke RM, Liscum L |
Journal of lipid research | 2009 |
Inhibition of hepatic stellate cell proliferation by heat shock protein 90 inhibitors in vitro.
Sun X, Zhang XD, Cheng G, Hu YH, Wang HY |
Molecular and Cellular Biochemistry | 2009 |
Natural killer cell receptors and their ligands in liver diseases.
Yamagiwa S, Kamimura H, Ichida T |
Medical Molecular Morphology | 2009 |
Platelet-activating factor involvement in thioacetamide-induced experimental liver fibrosis and cirrhosis.
Karantonis HC, Gribilas G, Stamoulis I, Giaginis C, Spiliopoulou C, Kouraklis G, Demopoulos C, Theocharis SE |
Digestive Diseases and Sciences | 2009 |
The GABAB receptor inhibits activation of hepatic stellate cells.
Xiao F, Yu K, Dong F, Liang Y, Jun C, Wei H |
Digestive Diseases and Sciences | 2009 |
Effect of anluohuaxian tablet combined with gamma-IFN on schistosomal liver fibrosis.
Huang J, Huang H, Jiao Y, Ai G, Huang T, Li L, Yu H, Ma K, Xiao F |
2009 | |
Reversal of liver fibrosis.
Ismail MH, Pinzani M |
Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association | 2009 |
Activated hepatic stellate cells promote tumorigenicity of hepatocellular carcinoma
Amann T, Bataille F, Spruss T, Mühlbauer M, Gäbele E, Schölmerich J, Kiefer P, Bosserhoff A, Hellerbrand C |
Cancer Science | 2009 |