Zinc Sulphate in Treatment Fibrosis in HBV Patient Receiving Antiviral Therapy

Hepatitis B virus (HBV) is a serious public health problem worldwide and major cause of chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). It was estimated that approximately 2 billion people have serological evidence of past or present HBV infection. More than 350 million are chronic carriers of HBV. (1)

Chronic hepatitis B describes a spectrum of disease usually characterized by the presence of detectable hepatitis B surface antigen (HBsAg) in the blood or serum for longer than 6 months. In some people, chronic hepatitis B is inactive and does not present significant health problems, but others may progress to liver fibrosis, cirrhosis and HCC. (1)

Liver fibrosis due to viral or metabolic chronic liver diseases is a major challenge of global health. Correlating with liver disease progression, fibrosis is a key factor for liver disease outcome and risk of HCC. (2)

Removal or elimination of the causative agent such as control or cure of viral infection has shown that liver fibrosis is reversible. There is a huge unmet medical need for anti-fibrotic therapies to prevent liver disease progression and HCC development. (2) Liver fibrosis is the excessive accumulation of extracellular matrix proteins including collagen that occurs in most types of chronic liver diseases. In the case of chronic HBV infection, ongoing liver inflammation and immune-mediated damage led to fibrosis over time. (2) Zinc is an essential trace element required for normal cell growth, development, and differentiation. It is involved in DNA synthesis, RNA transcription, and cell division and activation. It is a critical component in many zinc protein/enzymes, including critical zinc transcription factors. Zinc deficiency/altered metabolism is observed in many types of liver disease, including alcoholic liver disease and viral liver disease. (3) Serum zinc levels are significantly decreased in patients with acute hepatitis B infection and are frequently depressed with HBV cirrhosis (similar to HCV cirrhosis). Specifically designed zinc finger proteins had been used in an attempt to inhibit HBV viral transcription with some success, and this is a potential therapeutic target for new HBV drugs. Importantly, marginal zinc deficiency appears to impair the efficacy of hepatitis B vaccination. This is another example of how zinc deficiency may impair immune function with special relevance to liver disease. (3) Zinc supplementation suppresses the progression of liver fibrosis induced by bile duct ligation in mice. (4) Liver biopsy is recognized as the gold standard for disease monitoring; however, the procedure is invasive and bedeviled with potential complications. For these reasons, non-invasive biomarkers of fibrosis are now being evaluated as alternatives to liver biopsy. (5) Fibronectin is a glycoprotein involved in wound healing and extracellular matrix formation. Elevated levels are associated with liver fibrosis due to increased extracellular matrix deposition. It reflects fibrogenesis activity and can serve as an early indicator of fibrotic progression or regression. (6) Serum hyaluronic acid (HA) level is a precise predictor of extensive liver fibrosis in chronic hepatitis B. Stage of fibrosis is well correlated with HA which can reflect the severity of fibrosis. Thus, it can be used as a noninvasive test to monitor these patients. (7)