title: Early to Phase II drugs currently under investigation for the treatment of liver fibrosis.
abstract: BACKGROUND
  Chronic liver diseases represent a high unmet medical need and are characterized by persistent inflammation, parenchymal damage and fibrotic remodeling, leading eventually to cirrhosis and hepatic failure. Besides the persisting high prevalence of chronic viral hepatitis B and C, the dramatic increase in nonalcoholic steatohepatitis is now considered to be a major pathophysiologic driver for fibrosis development and subsequently cirrhosis. Increasing evidence suggests that also liver cirrhosis can regress when treated adequately.
  
  
  METHODS
  Herein, the authors review the underlying pathophysiologic mechanisms leading to fibrotic remodeling in the liver. They also highlight the options for novel treatment strategies by using molecular targeted agents.
  
  
  CONCLUSIONS
  New in vitro and preclinical animal models, and the careful selection of patients with high disease dynamics for clinical studies, provide a sound basis for the clinical development of antifibrotic agents in humans. Surrogate parameters of liver function, inflammation, tissue remodeling and damage, as well as noninvasive imaging techniques, can be applied in clinical trials to provide fast readouts and novel and reliable endpoints for trial design, and provide an attractive regulatory environment for this emerging disease area.
authors.affiliation: Bayer Pharma AG , Berlin , Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hauff
authors.forename: Ulrich
authors.initials: U
authors.lastname: Gottwald
authors.forename: Matthias
authors.initials: M
authors.lastname: Ocker
mesh_terms: D000818:Animals; D017322:Clinical Trials, Phase II as Topic; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000503:physiopathology; D008111:Liver Function Tests; D058990:Molecular Targeted Therapy; D018579:Patient Selection
keywords: cirrhosis; clinical trials; end-stage liver disease; liver fibrosis; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis