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Cheng et al. Advances in liver fibrosis

isoform of TGF-β by means of monoclonal antibodies can modify the natural history of chronic liver diseases,
is also feasible. Activation of TGF-β receptors can and more importantly, to improve patient outcome in
be inhibited by the use of specific inhibitors, thereby the near future.
halting downstream signaling. Local activation of
TGF-β induced by αvβ6 integrin and by tropomyosin- DECLARATIONS
related kinase (TSP)-1 can be prevented. [151]
The amino acid sequence Leu-Ser-Lys-Leu (LSKL) Authors’ contributions
naturally occurs in the region of the amino terminus of Drafting of the manuscript: J.Y.K. Cheng, G.L.H. Wong
the LAP and that it can hamper the activation of latent Critical revision of the manuscript for important
TGF-β by TSP-1 through competitive inhibition. [152] intellectual content: J.Y.K. Cheng, G.L.H. Wong
LSKL peptides significantly decrease DMN-induced
liver atrophy and fibrosis in an animal model. [153] Yet Financial support and sponsorship
LSKL has not been developed clinically. More recently None.
nanoconjugate siRNA against TGF-β1 equipped with
an N-acetylglucosamin targeting moiety intending to Conflicts of interest
reach HSCs via desmin was reported to colocalize with
HSCs and to reduce liver fibrosis. [154] Grace L.H. Wong has served as an advisory committee
member for Gilead Sciences. She has also served as
Connective tissue growth factor inhibitor a speaker for Abbott, Abbvie, Bristol-Myers Squibb,
CTGF is a mediator of ECM accumulation and Echosens, Furui, Gilead Sciences, Janssen and
coordinates a late common pathway to fibrosis. [155] Roche.
Blocking connective tissue growth factor (CTGF)
activity reduces liver fibrosis and preserves liver Patient consent
function. [156] FG-3019 is a recombinant human anti- Not applicable.
CTGF monoclonal immunoglobulin G antibody. FG-
3019 reduces collagen deposition in nonclinical Ethics approval
models of liver. FG-3019 was tested in CHB patients Not applicable.
in a Phase 2 randomized trial; unfortunately the study
terminated due to an unexpected prominent effect of REFERENCES
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164 Hepatoma Research ¦ Volume 3 ¦ August 08, 2017