A guide to pathophysiology, signaling pathways, and preclinical models of liver fibrosis

Liver fibrosis is potentially a reversible form of liver disease that evolved from the early stage of liver scarring as a consequence of chronic liver injuries. Recurrent injuries in the liver without any appropriate medication cause the injuries to get intense and deeper, which gradually leads to the progression of irreversible cirrhosis or carcinoma. Unfortunately, there are no approved treatment strategies for reversing hepatic fibrosis, making it one of the significant risk factors for developing advanced liver disorders and liver disease-associated mortality. Consequently, the interpretation of the fundamental mechanisms, etiology, and pathogenesis is crucial for identifying the potential therapeutic target as well as evaluating novel anti-fibrotic therapy. However, despite innumerable research, the functional mechanism and disease characteristics are still obscure. To accelerate the understanding of underlying disease pathophysiology, molecular pathways and disease progression mechanism, it is crucial to mimic human liver disease through the formation of precise disease models. Although various in vitro and in vivo liver fibrotic models have emerged and developed already, a perfect clinical model replicating human liver diseases is yet to be established, which is one of the major challenges in discovering proper therapeutics. This review paper will shed light on pathophysiology, signaling pathways, preclinical models of liver fibrosis, and their limitations.