الفهرس 
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Abstract
Levels) and haemoglobin.
Summary
• Thesis title: Association of Vitamin D Receptor Gene Polymorphisms (BsmI and Fok1) with HCV Quantitation by Real Time PCR in HCV Patients under Treatment with Sovaldi
• Hepatitis C : HCV is a liver disease caused by the hepatitis C virus this virus can cause both acute and chronic hepatitis, ranging in severity from a mild illness lasting a few weeks to a serious, lifelong illness (Roger et al., 2021). The hepatitis C virus is a blood borne virus and the most common modes of infection are through exposure to small quantities of blood. This may happen through injection drug use, unsafe injection practices, unsafe health care, and the transfusion of unscreened blood and blood products (Bunz et al., 2022). Globally, an estimated 171 million people have chronic hepatitis C infection. A significant number of those who are chronically infected will develop cirrhosis or liver cancer. Approximately (399.000) people die each year from hepatitis C, mostly from cirrhosis and hepatocellular carcinoma.(Wang et al., 2021) Antiviral medicines can cure more than 95% of persons with hepatitis C infection, thereby reducing the risk of death from liver cancer and cirrhosis, but access to diagnosis and treatment is low (Shimotohno, 2021). There is currently no vaccine for hepatitis C; however research in this area is ongoing.(Alshuwaykh and Kwo, 2020) Hepatitis C virus (HCV) causes both acute and chronic infection. Acute HCV infection is usually asymptomatic, and is only very rarely (if ever) associated with life-threatening disease. About 15–45% of infected persons spontaneously clear the virus within 6 months of infection without any treatment . The remaining 60–80% of persons will develop chronic HCV infection. Of those with chronic HCV infection, the risk of cirrhosis of the liver is between 15–30% within 20 years .(Haykal et al., 2021) HCV is a major cause of liver disease worldwide and a potential cause of substantial morbidity and mortality in the future. The complexity and uncertainty related to the geographic distribution of HCV infection and chronic hepatitis C, determination of its associated risk factors, and evaluation of cofactors that accelerate its progression, underscore the difficulties in global prevention and control of HCV .
• Vitamin D: It’s no longer a secret that vitamin D has effects beyond those on calcium and bone homeostasis. Since the vitamin D receptor is expressed on immune cells (B cells, T cells, and antigen presenting cells), and all of these immune cells are capable of creating the active vitamin D metabolite, it is possible that vitamin D works in an auto-crine manner in a local immunologic milieu..(Youssef et al., 2018). Vitamin D may have effects on the immune system’s innate and adaptive responses. Vitamin D insufficiency has been associated to increased autoimmune disease and increased infection susceptibility. It has been shown that immune cells in autoimmune diseases are responsive to the ameliorative effects of vitamin D, suggesting that the benefits of vitamin D may extend beyond those on bone and calcium homeostasis...(Feld and Ward, 2021) Tolerance to self is maintained while protective immunity is fostered by the immune system in its fight against invading pathogens. Increased vulnerability to infection and adiathesis in a genetically predisposed host to autoimmunity are only Vitamin D insufficiency has been related to two immune system problems in recent years...(Deffieu et al., 2022) Bone health and calcium homeostasis are two of vitamin D’s traditional activities. Vitamin D aids in the absorption of calcium in the digestive tract and stimulates the formation of osteoclasts, which are responsible for the reabsorption of calcium from bone. Bones’ collagen matrix is mineralized in part thanks to vitamin D. Vitamin D may come from food or from the body’s own natural production in the skin.
• Sovaldi (Sofosbuvir) : The introduction of sofosbuvir marked a major improvement in the care of patients with chronic hepatitis C. Since sofosbuvir only takes a single dose and may be administered as required without adverse effects, it represents a viable therapy option for those with advanced liver disease. The first and only all-oral medication for hepatitis C is sofosbuvir in conjunction with ribavirin. An lengthier term of all-oral therapy is required for genotype 3 infection, and it should be noted that genotype 3 seems to have less activity than genotype 2. The use of sofosbuvir as part of fixed-dose combinations is now the standard treatment...(Brener et al., 2020)
• Class and mechanism : Sofosbuvir is an analogue of a nucleotide that blocks the activity of NS5B polymerase, a key enzyme in the replication of HCV RNA. More than 90% of the total systemic exposure of sofosbuvir is due to its rapid metabolism in the body into the active form of the medicine, GS-331007. Absorption of GS-331007 is enhanced in hepatocytes, and Once within the cell, uridine analogue 5’-triphosphate is converted to the pharmacologically active form by cellular kinases (GS-461203). HCV uses a protein called HCV-T to trigger chain termination in the growing RNA primer strand. RNA polymerase integrates this triphosphate molecule, which is similar to the natural biological uridine nucleotide...(Syed et al., 2021) In its active form, GS-461203 is a chain terminator that selectively binds to the NS5B catalytic region. To the contrary, GS-461203, the active chemical, does not inhibit host DNA polymerases, RNA polymerases, or mitochondrial RNA polymerase.