Preclinical Promise and Clinical Challenges for Innovative Therapies Targeting Liver Fibrogenesis

Abstract

Liver fibrosis resulting from chronic liver injury can progress to cirrhosis and liver failure. Current treatments are limited, creating an urgent need for novel antifibrotic therapies. Multiple emerging approaches have shown preclinical promise in inhibiting liver fibrogenesis or stimulating regeneration, including artificial liver support, stem cell therapy, cell/gene therapy, nanomedicines, immunotherapy, and herbal medicines. Artificial liver support provides detoxification but has shown inconsistent transplant bridging benefits. Stem cell transplantation demonstrates antifibrotic paracrine effects and differentiation potential. Cell therapy with hepatocytes or modulatory immune cells, as well as genetic engineering approaches, aims to replace damaged cells or suppress inflammation. Nanoparticles enable targeted delivery of antifibrotic drugs and genes. Immunotherapy using checkpoint inhibitors, vaccines, or engineered cells can attenuate fibrogenesis-related inflammation. Some traditional Chinese herbal formulas and compounds exhibit antifibrotic, anti-inflammatory, and regenerative mechanisms. Despite encouraging preclinical data, most novel antifibrotic therapies have yet to achieve clinical translation, limited by challenges in safety, delivery, and efficacy. Combination treatment regimens may provide maximal therapeutic impact. Ongoing optimization and rigorous clinical evaluation are needed to develop effective new antifibrotic therapies for patients with chronic liver disease.