Introduction: 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.
Areas covered: 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.
Expert opinion: 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.
Keywords: cirrhosis; clinical trials; end-stage liver disease; liver fibrosis; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis.