Liver renewal: detecting misrepair and optimizing regeneration.

UNLABELLED: Cirrhosis and liver cancer, the main causes of liver-related morbidity and mortality, result from defective repair of liver injury. This article summarizes rapidly evolving knowledge about liver myofibroblasts and progenitors, the 2 key cell types that interact to orchestrate effective repair, because deregulation of these cells is likely to be central to the pathogenesis of both cirrhosis and liver cancer. We focus on cirrhosis pathogenesis because cirrhosis is the main risk factor for primary liver cancer. Emerging evidence suggests that the defective repair process has certain characteristics that might be exploited for biomarker development. Recent findings in preclinical models also indicate that the newly identified cellular and molecular targets are amenable to therapeutic manipulation. Thus, recent advances in our understanding about key cell types and fundamental mechanisms that regulate liver regeneration have opened new avenues to improve the outcomes of liver injury. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01899859.