**3. Conclusions/concluding remarks**

Non-alcoholic fatty liver disease is the most common liver disease in the western world. Yet, the mechanisms underlying the pathogenesis of this formidable is largely vague, thus lacks effective treatment so far. HSPGs are the main constituent of the extracellular matrix, and play important roles in liver pathologies, through cellcell and cell-ECM interactions, besides their role in uptake and processing of lipid particles by the liver cells. Heparanase is the enzyme that degrades heparan sulfate side chains in HSPGs, involves in remodeling of structure and alter the function of the HSPG macromolecules. Heparanase inhibition was proved to exert favorable results in different pathologies, including malignant diseases, complications of diabetes mellitus, kidney pathologies, inflammatory processes, and vessel wall pathologies like atherosclerosis. Recently we have demonstrated remarkable attenuation in the development of fatty liver in animal models with the use of two different heparanase inhibitors, an additional evidence for the involvement of heparanase in the development of fatty liver, putting heparanase inhibition as a reliable target for future research concerning the development of possible effective treatment for NAFLD. It could be wise to impliment heparanase inhibition as a part of treatment approach for preventing and treating NAFLD, along with restriction of lipid uptake, preventing

weight gain and weight, and optimal control of additional conditions that contribute to the development of NAFLD, such insulin resistance and diabetes mellitus.
