Study to Evaluate the Possible Antifibrotic Effect of Zinc Sulphate in Chronic HCV Patient Receiving Direct Acting Anti-viral Therapy.

This study aims to evaluate the possible antifibrotic effect of zinc sulphate in chronic HCV patient receiving direct acting anti-viral therapy

Chronic infection with hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide and predisposes to liver fibrosis and end-stage liver complications. Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, and is considered as a wound healing response to chronic liver injury. Removal or elimination of the causative agent such as control or cure of viral infection has shown that liver fibrosis is reversible. Thus, there is a huge unmet medical need for anti-fibrotic therapies to prevent liver disease progression and Hepatocellular Carcinoma (HCC) development. However, while many anti-fibrotic candidate agents have shown robust effects in experimental animal models, but uptill now, no approved therapy exists for liver fibrosis. The once-daily oral combination of Daclatasvir 60 mg and Sofosbuvir 400 mg once daily, for the treatment of non-cirrhotic naïve patients with chronic hepatitis C virus genotype 4 infection for 12 weeks, is effective and well tolerated in these patients. Zinc, an essential trace element, is involved in the enzymatic activities and structural maintenance of numerous enzymes and proteins, and it has various physiological roles in the body. Specifically, zinc works as a growth factor and exerts immunomodulatory , antioxidant, anti-apoptotic and anti-inflammatory effects. Zinc deficiency is prevalent in cirrhosis patients, whereas nitrogen metabolic disorders, particularly hypoalbuminemia, can be an indicator of zinc deficiency. Zinc supplementation therapy has a great benefit in the management of chronic liver disease and seems to improve liver pathology and reduce the incidence of liver fibrosis and HCC. It has been found that zinc supplementation inhibited liver inflammation and fibrosis in bile duct ligation (BDL) mice through selective suppression of M1 macrophages. Therefore, oral zinc supplementation is recommended as a means of suppressing HCC development in patients who have achieved sustained virological response (SVR) after direct acting antiviral therapies (DAAs) treatment . Zinc is a powerful supplement not only to increase SVR in non-responders but also to improve hepatic functions and fibrosis. Fibronectin (FN), which is produced by hepatic stellate cells (HSCs), is a multifunctional glycoprotein and extracellular matrix (ECM) component that is present in the cell membrane and cytoplasm and associated with cell cycle progression, participates in cell adhesion and proliferation, and has an important role in fibrotic progression, excessive FN deposition occurs prior to collagen deposition. Fibronectin expression was gradually increased in response to TGFβstimulation of HSCs, It is a good noninvasive marker for the assessment of liver fibrosis in patients with chronic HCV. Transforming growth factor (TGF)-β is a master profibrogenic cytokine and a promising target to treat fibrosis. Hyaluronic acid is a chief component of the extracellular matrix (ECM) of connective tissues and plays the main structural role in the formation of ECM. The most important organ involved in the synthesis of hyaluronic acid is the liver and the results of clinical studies have shown its high diagnostic sensitivity in the pathological processes of the liver.