Skip to main content

Table 1 Therapeutic and diagnostic options based on newly identified pathogenetic mechanisms of liver fibrosis

From: Evolving concepts of liver fibrogenesis provide new diagnostic and therapeutic options

Parameter Pathobiochemical basis Potential serum markers of fibrosis Therapeutic approach
TGF-β Fibrogenic master cytokine, up-regulation in fibrotic liver; inducer of epithelial-mesenchymal transition (EMT) Elevation by up-regulation in the fibrotic liver, release from necrotic hepatocytes and reduced hepatic clearance Inhibition of TGF-β, blockade of intracellular signalling
BMP-7 TGF-β antagonist: anti-apoptotic; anti-inflammatory; anti-EMT Elevation in serum, indicator of slow fibrosis? BMP-7 or BMP-7 peptide fragments antagonize TGF-β, antifibrotic effect, stimulation of liver regeneration
TGF-β/BMP-7 Ratio Determines epithelial-mesenchymal transition (EMT) and profibrogenic action of TGF-β Potentially of prognostic significance for estimation of the progression rate of fibrosis (rapid versus slow fibrosis) Modulation of the ratio by addition of recombinant BMP-7 has an antifibrotic effect
CTGF Down-stream modulator protein of TGF-β, influences functional TGF-β/BMP-7 ratio by elevation of TGF-β and decrease of BMP-7 action Elevation under conditions of active fibrogenesis, decrease with advancing cirrhosis and in the terminal stage without fibrogenic activity Inhibition of CTGF expression by siRNAs or blocking with humanized monoclonal anti-CTGF antibodies (FG-3019, FibroGen); has a strong antifibrotic effect
Fibrocytes Bone marrow-derived progenitor cells of fibroblasts increase the pool of fibroblasts in the fibrotic liver Flow-cytometric detection of CD34+, CD45+, and collagen-1+ cells in peripheral blood or buffy coat leucocytes; potential indicator of increased influx into the damaged liver tissue Hormonal modulation of release of fibrocytes from bone marrow and integration into the liver?
G-CSF Recruitment of bone marrow-derived cells in the circulation and stimulation of their homing in the fibrotic liver tissue Elevated concentrations, relation to fibrogenesis not yet established G-CSF triggered haematopoietic stem cells or G-CSF itself accelerates healing of experimental liver damage and improves the survival rate