Liver fibrosis can be categorized as a serious health problem worldwide. It is widely recognized that activated hepatic stellate cells (HSC) play a pivotal role in pathological development of liver fibrosis. The activated hepatic stellate cells (aHSCs) are main producers of ECM, which play a significant role in scarring process of the liver derived from variety of etiologies, such as hepatitis B or C virus infection, chronic alcohol abuse, non-alcoholic steatohepatitis, cholestasis, and autoimmune hepatitis. Due to lack of effective treatments, chronic liver diseases and liver fibrosis can eventually progress to liver cirrhosis and even liver cancer. Inhibition of the stellate cell proliferation, differentiation and prevention of its activation is appealing as an ideal strategy for ameliorating hepatic fibrosis. A platelet-derived growth factor (PDGF) is the most potent proliferating stimulus for HSC. Imatinib mesylate (Gleevec), a clinically used PDGF receptor (PDGFR) tyrosine kinase inhibitor could be a promising molecular targeted approach to limit the liver fibrosis development. IL-6/STAT3 is one the pivotal signaling pathways for the activation of HSCs. Herein in our previous study we found that Imatinib upregulates miR-124 and interferes simultaneously with STAT3-HLF-IL-6 pathway. However, due to effective role of imatinib in blocking two important liver fibrosis related pathways, pharmacokinetics of imatinib in patients with liver fibrosis have never been assessed. This study is a phase I/II, double blind labeled, randomized, double arms clinical trial. Consequently, this phase I/II trial was initiated to evaluate the safety and efficacy of imatinib in patients with advanced liver fibrosis. 20 patients with clinical and/or pathologic diagnosis of liver fibrosis grade 3-4 will be registered at Taleghani hospital (Tehran). 10 patients will receive standard medication and imatinib for 24 weeks at the dose of 200mg/day orally. Another 10 patients will be treated with standard medication of liver fibrosis and placebo of imatinib drug as a control group.
When a recurrent, long-term injury and inflammation of the liver causes an excessive accumulation of damaged tissue, a dangerous condition called liver fibrosis develops. Most chronic liver diseases eventually lead to fibrosis. Activated hepatic stellate cells (aHSC) play an important role in the development of hepatic fibrosis. Inhibiting the proliferation of stellate cells and preventing their differentiation and activation is an ideal strategy for ameliorating hepatic fibrosis. Hence imatinib have been prescribed as a promising drug to limit the progression of liver fibrosis as a clinical inhibitor of tyrosine kinase which can affect the two main pathways leading to hepatic stellate cells activation.