Anti-fibrotic therapy: lost in translation?
While preclinical development of potential anti-fibrotics is far advanced, with numerous pharmacological targets and promising agents, almost none has entered clinical validation. Reasons are manifold, including the usually slow progression of liver fibrosis, requiring high numbers of well-stratified patients undergoing long-term treatment when conventional liver biopsy based parameters or hard liver-related endpoints are used. Importantly, there is a notorious lack of sensitive and specific surrogate markers or imaging technologies for liver fibrosis progression or regression that would permit a rapid clinical screening for potential anti-fibrotics. Nonetheless, in view of an urgent need for anti-fibrotics that positively impact morbidity and mortality from chronic liver diseases, the field is now moving more quickly towards clinical translation. This development is driven by thoughtful preclinical validation, a better study design and improved surrogate readouts using currently available methodologies. Moreover, upcoming novel biomarkers and imaging technologies will soon permit a more exact and efficient assessment of fibrosis progression and regression.
Division of Molecular and Translational Medicine, Dept. of Medicine I, University of Mainz Medical School, Mainz, Germany. detlef.schuppan@unimedizin-mainz.de
Detlef
D
Schuppan
Massimo
M
Pinzani
D000818:Animals; D015415:Biomarkers; D004195:Disease Models, Animal; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control*; D008279:Magnetic Resonance Imaging; D018579:Patient Selection; D057170:Translational Research, Biomedical
D015415:Biomarkers