Liver fibrosis is a wound healing scar response following acute and chronic liver diseases including chronic hepatitis B and C, autoimmune hepatitis, non-alcoholic steatohepatitis and alcoholic liver disease. The patho-histological findings of liver cirrhosis, the end-stage of liver fibrosis, show hepatocellular death, a lobular inflammatory cell infiltrate, excessive deposition of extracellular matrix (ECM) proteins, and the appearance of regenerative nodules that may result in liver failure, portal hypertension and hepatocellular carcinoma. The pathophysiology of liver injury has attracted the interest of experimentalists and clinicians over many centuries.  With the discovery of liver- HSC, the insight into the cellular and molecular pathobiology of liver fibrosis has evolved and the pivotal role of Hepatic Stellate cell (HSC) as a precursor cell-type for ECM–producing myofibroblasts has been established.. Although activation and trans-differentiation of HSC to myofibroblasts (MFs) is still regarded as the pathogenetic key mechanism of fibrogenesis, recent studies point to a prominent heterogeneity of the origin of myofibroblasts . The newly discovered pathways supplement the concept of HSC activation to myofibroblasts (MFs), point to fibrosis as a systemic response involving extrahepatic organs (lung and kidney) and reactions, and offer innovative approaches for the development of non-invasive biomarkers and anti-fibrotic agents.