HCV or Hepatitis C virus infection has over 5 million people affected in US (Chak, et al., 2011) and over 120 million people worldwide hence a global health problem. This virus belongs to Hepacivirus genus and Flaviviridae family (Lindenbach, et al., 2007) with six genotypes and with more than seventy subtypes. In approximately 85% infected individuals it may be unresolved, hence representing a significant hepatocellular carcinoma and liver cirrhosis cause. It is viewed as commonest cirrhosis cause and chronic liver disease in the world. It also represents the main liver transplantation cause in USA, Europe, and Australia (Thimme, et al., 2001). Through HCV-RNA demonstration in blood for a minimum of six months after virus contamination is chronic infection proved (Chen and Morgan, 2006). Those who show chronic liver disease's laboratory or clinical signs must get a chronic HCV infection diagnosis via both HCV-RNA and anti-HCV antibodies demonstration (EASL International Consensus Conference on Hepatitis C, 1999). HCV transmission is caused mainly through infected blood or its products. Other risks however, have got demonstrated for the infection of HCV which get represented through illicit drugs intravenous use haemodialysis, and HCV-infected organ transplantation. HCV infection which is less frequent has got documented as a result of contaminated blood occupational exposure. There has also been publication of HCV sporadic report due to intranasal cocaine use, unsafe sex, vertical transmission and household exposure.
In the course of viral infection, there are various cytokines which do play their role in both tissue damage and viral clearance (Steinke and Borish, 2006). There are over one hundred reported cytokines, which get classified on the basis of their primary role. Cytokines, in relation to their roles, they play a significant function during HCV infection pathogenesis, progression and outcome of treatment. Multiple biomarkers screening could best clarify disease immunopathogenesis and predict antiviral therapy responses because cytokines production control is highly complex and cytokines effects are spread widely through multiple networks of regulation (Nathan, et al., 1983). Immune response which is conducted essentially by cytokines may be able to play a significant function in HCV infection pathogenesis. A strong Th1 response which is characterized by interferon-gamma, tumor necrosis factor-alpha and interleukin-2 production is associated with clearance of HCV (Saito and Gale, 2008).
Certain information has recommended that cytokines contribute to autoimmunity, hepatic injury and even HCV persistence (Gramenzi, et al., 2005). Chronic HCV infection patients posses a T-cell response activated cytokine pattern, which has elevated serum levels of interferon gamma, tumor necrosis factor alpha, IL-2, IL-4, and IL-10. Severe chronic liver cirrhosis or hepatitis C patients poses an enhanced IL-2 and interferon gamma expression compared to individuals having mild disease and healthy controls (Napoli, et al., 1996). Essentially, cytokines conducted immune response plays a significant role in HCV infection pathogenesis. A strong Th1 response that is characterized by interferon gamma, tumor necrosis factor alpha, and IL-2 production does seems to have HCV clearance association (Mosmann, 1996). However, they may be seen responsible for damage of the liver during a persistent infection. There has been reported an important circulating and intrahepatic Th1 type cytokines correlation with liver injury degree (Tao, et al., 1997).
The cytokine which plays a major role in angiogenesis and collagen synthesis suppression, and in Th1 cell differentiation enhancement is the interferon gamma that is made by the Th1 cells (Reitamoet, et al., 1994). Forty eight weeks HCV infected patients treatment with interferon gamma leads to approximately 20% sustained response rates. Virologic response related factors include gender, liver biopsy degree of fibrosis, HCV ribonucleic acid level pretreatment, and HCV genotype. Interferon gamma production get controlled by APCs secreted cytokines, most notably IL-15 and IL-2. These cytokines do serve as an infection link bridge with production of interferon gamma in inmate immune response.
Immune response which is conducted by cytokines plays a significant HCV infection pathogenesis role. A strong Th1 response that is characterized by interferon gamma, tumor necrosis factor alpha, and IL-2 production does seems to have HCV clearance association. IL-10, IL-13, 1L-5, and IL-4 are produced by Th2 cells that limit Th1 response and facilitate antibody production. Our analysis of cytokine showed that adaptive immunity, is able to promote significantly Th2 and Th1 cells to secrete IL-10 and interferon gamma elevated levels in positive patients with HCV infection(Del Prete, et al., 1994). Th1 lymphocytes, which are characterized by tumor necrosis factor alpha, interferon gamma, and interleukin IL-2 predominant secretion are involved in cytotoxic T-lymphocye responses and cellular immunity, Th2 cells that modulate humoral responses via IL-13, IL-10, IL-5, and IL-4 production (Del Prete, et al., 1994).
In this study, the highest human interferon gamma serum levels got observed in positive patients with HCV infection (p < 0.05). The interferon gamma observed increase in positive patients of HCV infection, it is as a result of replication of HCV virus, and progression of the disease, according to the previous reports observation (Posta, et al., 2009). The important cd4+ helper T cells role in spontaneous mediation of viral clearance got demonstrated through several observations. Proliferation of CD4+ helper T cell loss responses in the context of acute HCV had an association with chronic infection development and viral recurrence, in one of them (Gerlach, et al., 1999). That reason explains IL-10 concentration in this study's result was found to be significantly lower compared to the concentration of interferon gamma in positive patients of HCV infection. On the other hand, there was a revelation by cytokine analysis that humoral immunity according to the age of patient was significantly able to promote Th2 into secretion of IL-10 elevated levels in positive patients with HCV infection. And there was direct correlation seen between high IL-10 levels and age, as found in this particular project.
Being consistent with the previous reports in this study showed that AST enzymes activity got increased significantly with interferon gamma in positive patients with HCV infection compared to control group (Missiha, et al., 2008). The higher AST levels of serum observed in the positive patient with HCV infection suggest a chronic HCV co-infection synergistic effect in the damage of liver cells. Some results got also reported for HCV (Petrova, et al., 2010).
Some authors suggested that ALT/AST ratio is correlated strongly with portal fibrosis level in HCV patients who are non uremic (Sheth, et al., 1998). It is also stated that this ratio has no correlation with liver's necroinflamatory activity, and a ratio which is less than 1 does exclude cirrhosis and severe fibrosis patients (Sheth, et al., 1998). In this study ALT?AST was an important marker in patients having HCV infection. HCV infection's natural outcome varies among individuals dramatically. In fortunate minority, HCV infection seems self limited, while in the majority subjects, do develop the persistent chronic infection (Seeff, 1997). Though HCV infection in adults does progress in about (Terrault,et al., 2008) five percent to chronic stage, in persistent infection of HCV individuals, majority do develop liver cancer, progressive fibrosis, and even CH (Vildozola and Salinas, 2009). However, other cases won't progress significantly to any liver disease (Kenny Walsh, 1999).
Cytokines have a crucial function to regulate inflammatory and immune responses. IL-10 and interferon gamma are Th1 cytokines and have powerful effect of immunoregulation on activation and proliferation stimulation of most B lymphocytes, natural killer cells, and T lymphocytes (Seder and Paul, 1994). According to some evidence IL-10 , interferon gamma, and IL-2 patients' levels with severe or moderate cirrhosis and CH are significantly decreased compared to those of the controls which are healthy (Polwaska, et al., 2005). Other authors observation is that increased IL-10, interferon gamma, and IL-2 expression has correlation with the staging or grading of chronic hepatitis. IL-10 and interferon gamma in this study increased significantly in positive patients with HCV infection (P < 0.05). HCV is usually a chronic viral infection which is unusual in individuals despite its treatment clearing the virus. Differing viremia control rates with treatment has enabled some human immunological questions which are interesting to be addressed, like those pertaining to CD4+ T-cell response nature and relationship and the antigen clearance kinetics.
It is accepted widely that CD4+ T-cell responses do have a major function in the noncytopathic viruses control. CD4+ T-cell responses which are HCV specific by interferon gamma production have ability to proliferate in HCV infection (Godkin, et al., 2008). T-cell role is marked by other cytokines production such asIL-17 or IL-2, the vast antiviral T-cells majority appear to produce and or proliferate interferon gamma (Bes, et al., 2012), this does with our interferon gamma result that is increased significantly in positive patients of HCV infection. Therefore, as it seems, other immune mechanisms should get activated via high dose interferon gamma exposure which are significant for clearance of the virus ( Su, et al., 2002) by numerous cell types which include dendritic cells, monocytes, macrophages, NK, IL-10 may donwregulate the processing of antigen by transporter associated having antigen processing, expressionof MCH and production of IL-2 by APC or antigen presenting cells, hence resulting to impaired T-cell proliferation, memory and effector function.
Additionally, serum changes or levels of T-cell IL-10 have association with the antiviral therapy efficacy in some studies. In this study the interferon gamma response which is HCV-specific strength is correlated with immunological. virological, and clinical parameters during the acute infection. Direct associations viremia, and sALT levels and interferon gamma which is HCV-specific as well as proliferation of CD4+ T-cell which is suppressed in this context of acute infection does suggest IL-10 response to be induced as a mechanism of compensation to dampen inflammation which is ongoing.
A study by (Luik, et al., 2004), identified interferon gamma response which is HCV-specific observed with HCV resolved infection. According to this suggestion T-cells which are HCV-specific are maintained on a similar antigenic hierarchy, scope and frequency in HCV infection which is chronic just like those found in recovered HCV infection though they are polarized toward production of IL-10 instead of production of interferon gamma characteristic of spontaneous clearance of HCV. The possible this finding's explanation include the T-cell maturation alteration as a result of antigen presenting cells virus induced dysfunction (Yakushijin, et al., 2006).
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