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Genetic testing is not yet a standard procedure for the identification of individual risks for spontaneous clearance or
Different investigational approaches have been used to identify genetic susceptibility factors for the natural course and treatment response in hepatitis C and B. Until the last decade the candidate gene approach was most frequently used. More recently genome wide association studies were applied to identify genetic predictors of spontaneous course and therapy outcome in chronic viral hepatitis C and B.
Cytokines represent a large family of molecules, including the chemokines, interleukins, interferons and members of the tumour necrosis factor (TNF) family, all which play an important role for the initiation and regulation of immune responses and, therefore, might affect susceptibility to and/or natural course of HCV infection.
Recently, allelic variants in the IL28B gene have gained major scientific interest as several genome-wide association studies identified a panel of single nucleotide
Chronic viral hepatitis C is difficult to cure and current standard treatment options suffer from variable success rates and considerable adverse effects [73]. A number of viral and clinical factors such as viral genotype, viral load, gender and stage of fibrosis have been identified as predictors of response. However, different studies suggest that genetically determined inter-individual differences in immune response may also have an impact on treatment outcome [4], [5], [6], [74], [75].
Current standard of care for chronic HCV infection is treatment with peginterferon and ribavirin. However, this therapy is hampered by a number of possible side effects. Two of the most common being anaemia and neuropsychiatric symptoms.
Ribavirin dose reduction due to anaemia is associated with poorer treatment outcome. Recently, variants in the inosine triphosphatase (ITPA) gene, which confers a corresponding enzyme deficiency, have been associated with anaemia in patients treated with
The influence of individual genetic characteristics on the course of HCV and probably also HBV became obvious by the recent discovery of the impact of genetic variants in the interferon-lambda pathway. These observations stress the importance of further in depth genetic analysis in the field of pharmacogenomics in order to improve current therapy standards. Genetic testing is not yet a standard procedure for the identification of individual risks for spontaneous clearance orPractice points
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As shown in Fig. 3A and C, compared with those immunized with the Ha prime-R boost regimen, HI mice immunized with the Hpa prime-R boost regimen exhibited greater S-specific production of IFN-γ and TNF-α by CD4+ T cells, and significantly greater production of TNF-α by CD8+ T cells. Cytokines play an important role in the initiation and regulation of immune responses and so may contribute to the inhibition of virus replication (Grunhage and Nattermann, 2010; Li et al., 2016). Thus, we evaluated cytokine levels in splenocyte culture supernatants at 2 weeks after the second immunization.
Finally, it is believed that the host genetic factors are the third agent which can change the outcomes of HBV infection. Although the effects of virological and environmental factors on HBV infection have been well known but the influence of the host genetic factors on susceptibility to HBV infection is not clearly understood (Dean et al., 2002; Grünhage and Nattermann, 2010; Hill, 1998a; Hill, 1998b; Mackay, 2006; McNicholl et al., 2000; Thursz, 1997; Thursz et al., 2011). Studies on identical twins reveals that host genetic factors can alter the natural history of HBV infection (Lin et al., 1989).
Thus predicting the likelihood of response of treatment before initiating therapy would be very useful to estimate the potential for treatment success [5]. Cytokines represent a large family of molecules which play an important role for the initiation and regulation of immune responses and, therefore, might affect susceptibility and response to treatment of HCV infection [6]. Many SNPs in genes encoding different cytokines have been reported to be associated with treatment effect [7], with some controversies [8].
They can help clinicians in the decision on whether or not to start antiviral therapy and this information can also motivate patients who might have a high chance for virological response. Cytokines represent a large family of molecules, including the chemokines, interleukins, interferons and members of the TNF family, all of which play an important role for the initiation and regulation of immune responses and, therefore, might affect susceptibility to and/or natural course of HCV infection [28]. The majority of previous studies concerning impact of cytokines on HCV focused on genotypes 1, 2 and 3.