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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Models of Liver Fibrosis: Exploring the dynamic nature of inflammation and repair in a solid organ
J. P. Iredale |
Journal of Clinical Investigation | 2007 |
Common and Unique Mechanisms Regulate Fibrosis in Various Fibroproliferative Diseases
Thomas A. Wynn |
Journal of Clinical Investigation | 2007 |
NOX in liver fibrosis
SD Minicis, DA Brenner |
Archives of Biochemistry and Biophysics | 2007 |
Fibrosis and cancer: Do myofibroblasts come also from epithelial cells via EMT?
DC Radisky, PA Kenny, MJ Bissell |
Journal of Cellular Biochemistry | 2007 |
Bioconjugation of Oligonucleotides for Treating Liver Fibrosis
Z Ye, HS Houssein, RI Mahato |
Oligonucleotides | 2007 |
The Effect of Ras Inhibition on the Proliferation, Apoptosis and Matrix Metalloproteases Activity in Rat Hepatic Stellate Cells
I Zvibel, D Bar-Zohar, Y Kloog, R Oren, S Reif |
Digestive Diseases and Sciences | 2007 |
The Myofibroblast
B Hinz, SH Phan, VJ Thannickal, A Galli, ML Bochaton-Piallat, G Gabbiani |
The American Journal of Pathology | 2007 |
Inflammation and Repair in Viral Hepatitis C
MG Neuman, K Sha, R Esguerra, S Zakhari, RE Winkler, N Hilzenrat, J Wyse, CL Cooper, D Seth, MD Gorrell, PS Haber, GW McCaughan, MA Leo, CS Lieber, M Voiculescu, E Buzatu, C Ionescu, J Dudas, B Saile, G Ramadori |
Digestive Diseases and Sciences | 2007 |
Evolving concepts of liver fibrogenesis provide new diagnostic and therapeutic options
OA Gressner, R Weiskirchen, AM Gressner |
Comparative hepatology | 2007 |
Biomarkers of hepatic fibrosis, fibrogenesis and genetic pre-disposition pending between fiction and reality
OA Gressner, R Weiskirchen, AM Gressner |
Journal of Cellular and Molecular Medicine | 2007 |
A new xenobiotic-induced mouse model of sclerosing cholangitis and biliary fibrosis
P Fickert, U Stöger, A Fuchsbichler, T Moustafa, HU Marschall, AH Weiglein, O Tsybrovskyy, H Jaeschke, K Zatloukal, H Denk, M Trauner |
The American Journal of Pathology | 2007 |
Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-β as major players and therapeutic targets
Gressner AM, Weiskirchen R |
Journal of Cellular and Molecular Medicine | 2007 |
Treatment of fibrosis in nonalcoholic fatty liver disease.
Hoteit MA, Anania FA |
Current Gastroenterology Reports | 2007 |
Different profiles of Ca2+responses to endothelin-1 and PDGF in liver myofibroblasts during the process of cell differentiation
N Kojima, M Hori, T Murata, Y Morizane, H Ozaki |
British Journal of Pharmacology | 2007 |
A ribosomal S-6 kinase-mediated signal to C/EBP-beta is critical for the development of liver fibrosis
M Buck, M Chojkier |
PloS one | 2007 |
Proangiogenic cytokines as hypoxia-dependent factors stimulating migration of human hepatic stellate cells
E Novo, S Cannito, E Zamara, LV di Bonzo, A Caligiuri, C Cravanzola, A Compagnone, S Colombatto, F Marra, M Pinzani, M Parola |
The American Journal of Pathology | 2007 |
Bone Morphogenetic Protein 7 is Elevated in Patients with Chronic Liver Disease and Exerts Fibrogenic Effects on Human Hepatic Stellate Cells
F Tacke, E Gäbele, F Bataille, RF Schwabe, C Hellerbrand, F Klebl, RH Straub, T Luedde, MP Manns, C Trautwein, DA Brenner, J Schölmerich, B Schnabl |
Digestive Diseases and Sciences | 2007 |
Simple Tests to Predict Hepatic Fibrosis in Nonalcoholic Chronic Liver Diseases
Shin WG, Park SH, Jun SY, Jung JO, Moon JH, Kim JP, Kim KO, Park CH, Hahn TH, Yoo KS, Kim JH, Park CK |
Gut and Liver | 2007 |
Gene Modulation for Treating Liver Fibrosis
Cheng K, Mahato RI |
Critical reviews in therapeutic drug carrier systems | 2007 |
Adeno-associated virus vector-mediated production of hepatocyte growth factor attenuates liver fibrosis in mice
Suzumura K, Hirano T, Son G, Iimuro Y, Mizukami H, Ozawa K, Fujimoto J |
Hepatology International | 2007 |
Sonic Hedgehog Is An Autocrine Viability Factor for Myofibroblastic Hepatic Stellate Cells
Yang L, Wang Y, Mao H, Fleig S, Omenetti A, Brown KD, Sicklick JK, Li YX, Diehl AM |
Journal of Hepatology | 2007 |
Cholangiocytes with Mesenchymal Features Contribute to Progressive Hepatic Fibrosis of the Polycystic Kidney Rat
Sato Y, Harada K, Ozaki S, Furubo S, Kizawa K, Sanzen T, Yasoshima M, Ikeda H, Sasaki M, Nakanuma Y |
The American Journal of Pathology | 2007 |
Tumor Necrosis Factor-α 308.2 Polymorphism Is Associated with Advanced Hepatic Fibrosis and Higher Risk for Hepatocellular Carcinoma
Jen-Eing J, Jung-Fa T, Lee-Yea C, Mei-Shang H, Zu-Yau L, Min-Yuh H, Shin-Chern C, Wan-Lung C, Liang-Yen W, Ming-Lung Y, Chia-Yen D, Jan-Gowth C |
Neoplasia (New York, N.Y.) | 2007 |
Pathophysiological characteristics of dimethylnitrosamine-induced liver fibrosis in acute and chronic injury models: a possible contribution of KLF5 to fibrogenic responses.
Ohara F, Nii A, Sakiyama Y, Tsuchiya M, Ogawa S |
Digestive Diseases and Sciences | 2007 |
Immunological response in alcoholic liver disease.
Duryee MJ, Klassen LW, Thiele GM |
World Journal of Gastroenterology | 2007 |
Role of iron in hepatic fibrosis: one piece in the puzzle.
Philippe MA, Ruddell RG, Ramm GA |
World Journal of Gastroenterology | 2007 |
Identification and functional characterization of the hepatic stellate cell CD38 cell surface molecule.
March S, Graupera M, Rosa Sarrias M, Lozano F, Pizcueta P, Bosch J, Engel P |
The American Journal of Pathology | 2007 |