Reversal of Hepatic Fibrosis — Fact or Fantasy?

The prospect of reversing hepatic fibrosis has generated great interest now that basic science advances are being translated into promising new antifibrotic therapies. It is appropriate to recognize both the historical advances that created the framework for these successes, and the important role that Hepatology has played in disseminating them. A sense of urgency underlies this effort as the epidemics of HCV and NASH are becoming associated with advancing fibrosis. To maintain progress and minimize confusion among investigators and clinicians it is essential to standardize terms referring to fibrosis 'reversal' and 'regression.' There must also be rapid optimization of non-invasive markers of fibrosis to relieve this current bottleneck to conducting clinical trials. Progress in identifying genetic determinants of fibrosis could further refine patient selection for clinical trials and shorten their duration, as well as unearthing new directions of scientific inquiry. Realistic expectations for successful anti-fibrotic therapies reflect solid evidence of fibrosis regression in patients treated effectively for viral liver disease, as well as growing clarity in the understanding mechanisms of extracellular matrix production and degradation. The paradigms of stellate cell activation and apoptosis remain valuable frameworks for understanding pathways of hepatic fibrogenesis and fibrosis regression, respectively. Continued progress is essential in order to identify the determinants and dynamics of fibrosis reversibility, to discover additional targets for anti-fibrotic therapy, and to develop customized multi-drug regimens. These advances are sure to be captured in the next 25 years by Hepatology , and to profoundly impact the prognosis of patients with chronic liver disease.