Chronic HCV Infection
Chronic infection with HCV is a major cause of liver disease and liver cancer worldwide (4) . In recent years, HCV infection has emerged as a major health problem in Egypt. It shows a strikingly high prevalence and was found to be the most important cause of chronic liver disease in Egypt (Reker and Islam,2014).Chronic HCV infection has been associated with a variety of extra-hepatic disorders, in which either immunological or cytopathic mechanisms are likely to play a role. For a few of these conditions, such as mixed cryoglobulinemia, porphyria cutanea tarda and autoimmune hepatitis, the link with HCV infection has been proven. For other manifestations, such as rheumatoid arthritis and idiopathic pulmonary fibrosis, this association has been
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disproved, For the remaining disorders, such as lichen planus, Sjogren's syndrome, and autoimmune thyroiditis, the evidence incriminating HCV is still being debated. Accordingly, it is postulated that HCV infection is not only a liver disease but rather a systemic infection that affects other organs of the body (6).
The association between HCV infection and development of DM has been observed ().
Although these clinical studies were set out to evaluate the role of HCV infection in the pathogenesis of DM, many questions remain unanswered (7). The increased prevalence of type 2 DM among patients with chronic HCV infection is independent of cirrhosis (7). The role of the direct cytopathic effect of HCV on β-cells in the development of DM was strongly supported by autoimmunity directed to β cells is usually present long before the clinical onset of DM. Either acute or persistent viral infection could trigger the autoimmune process, render the target cells vulnerable to autoimmune attack without necessarily causing an acute cell damage. This autoimmune hypothesis was disproved by Grimbert et al (1996) who found no significant statistical correlation between the presence of islet cell antibodies and HCV infection. This discrepancy among the different clinical studies about the role of HCV infection in the pathogenesis of DM could be attributed to that these works have been biased by the retrospective design of the studies and, more importantly, by lack of an adequately age- and gender- matched control …show more content…
group.
The host cellular immune defense, including CD4+ and CD8+ T-cell response, is activated in patients with HCV infection(8).(Penna et al.,2007).The intensity of the T-cell response during the early stages of infection may be a critical determinant of disease resolution and control of infection(10) In many cases, an infection is fought with both arms of the immune system.
At other times, one of them is predominantly controls the infection. In a healthy immune system both Th1 and Th2 are balanced to allows quick eradication of a threat and then a return to balance. After analyzing the results of this study we found that patients with DM and chronic HCV infection (were not receiving interferon therapy) (Group 2) had significantly elevated serum levels of IL-10 (Th2 marker) and significantly decreased serum levels of IL-2 (Th1 marker)compared with HCV patients only (Group I). Also, there is a highly significantly elevated serum level of IL 10 between the two groups than control subjects, and also highly significant decrease in levels of IL-2 between the first two groups and the third group (control group).This increase in serum IL-10 in patients with HCV , infection is in agreement with Eksioglu et al., (2010) who had reported that level of IL-10 production by CD4+ T cells in patients developing chronicity was significantly higher than control group. While, Laidlaw et al., (2015) was in agreement with our results. The elevation of IL-10 in the serum of the patients indicates that
Th2 like response play a role in chronic hepatitis C patients trying to ameliorate the tissue damaging effects of immune responses mediated by Th1 like responses (13) .Thus the interference against Th1 cells by increasing production of IL-10 might be one mechanism by which the host immune response is compromised in chronic HCV disease (Saraiva and O’Garra,2010).On the other hand, Kim et al., (2007) observed a down-regulation of IL -10 expression compared with normal
disproved, For the remaining disorders, such as lichen planus, Sjogren's syndrome, and autoimmune thyroiditis, the evidence incriminating HCV is still being debated. Accordingly, it is postulated that HCV infection is not only a liver disease but rather a systemic infection that affects other organs of the body (6).
The association between HCV infection and development of DM has been observed ().
Although these clinical studies were set out to evaluate the role of HCV infection in the pathogenesis of DM, many questions remain unanswered (7). The increased prevalence of type 2 DM among patients with chronic HCV infection is independent of cirrhosis (7). The role of the direct cytopathic effect of HCV on β-cells in the development of DM was strongly supported by autoimmunity directed to β cells is usually present long before the clinical onset of DM. Either acute or persistent viral infection could trigger the autoimmune process, render the target cells vulnerable to autoimmune attack without necessarily causing an acute cell damage. This autoimmune hypothesis was disproved by Grimbert et al (1996) who found no significant statistical correlation between the presence of islet cell antibodies and HCV infection. This discrepancy among the different clinical studies about the role of HCV infection in the pathogenesis of DM could be attributed to that these works have been biased by the retrospective design of the studies and, more importantly, by lack of an adequately age- and gender- matched control …show more content…
group.
The host cellular immune defense, including CD4+ and CD8+ T-cell response, is activated in patients with HCV infection(8).(Penna et al.,2007).The intensity of the T-cell response during the early stages of infection may be a critical determinant of disease resolution and control of infection(10) In many cases, an infection is fought with both arms of the immune system.
At other times, one of them is predominantly controls the infection. In a healthy immune system both Th1 and Th2 are balanced to allows quick eradication of a threat and then a return to balance. After analyzing the results of this study we found that patients with DM and chronic HCV infection (were not receiving interferon therapy) (Group 2) had significantly elevated serum levels of IL-10 (Th2 marker) and significantly decreased serum levels of IL-2 (Th1 marker)compared with HCV patients only (Group I). Also, there is a highly significantly elevated serum level of IL 10 between the two groups than control subjects, and also highly significant decrease in levels of IL-2 between the first two groups and the third group (control group).This increase in serum IL-10 in patients with HCV , infection is in agreement with Eksioglu et al., (2010) who had reported that level of IL-10 production by CD4+ T cells in patients developing chronicity was significantly higher than control group. While, Laidlaw et al., (2015) was in agreement with our results. The elevation of IL-10 in the serum of the patients indicates that
Th2 like response play a role in chronic hepatitis C patients trying to ameliorate the tissue damaging effects of immune responses mediated by Th1 like responses (13) .Thus the interference against Th1 cells by increasing production of IL-10 might be one mechanism by which the host immune response is compromised in chronic HCV disease (Saraiva and O’Garra,2010).On the other hand, Kim et al., (2007) observed a down-regulation of IL -10 expression compared with normal