Hepatic Gene Expression Discriminates Responders and Nonresponders in Treatment of Chronic Hepatitis C Viral Infection

Chen, Limin; Borozan, Ivan; Feld, Jordan J.; Sun, Jing; Tannis, Laura Lee; Coltescu, Catalina; Heathcote, Jenny; Edwards, A.M.; McGilvray, Ian

doi:10.1053/j.gastro.2005.01.059

“…Nevertheless, this information provides additional support for a relationship between host genetics and HCV viral clearance and is consistent with several recent reports that evaluated gene expression and gene polymorphisms in individuals with and without sustained virological response to interferon-based regimens (49)(50)(51)(52)(53)(54). Using microarrays in hepatic tissue, Chen and colleagues identified a number of interferon-sensitive genes that correlated with response to antiviral therapy (50). Similarly, among black and white patients with chronic hepatitis C treated with interferon, different patterns of expression of interferon-stimulated genes, such as 2,5-OAS, MxA, and PKR, were identified between individuals of African and European ancestry, suggesting potential mechanisms for diminished response to antiviral therapy seen in African American patients (55).…”

Section: Discussionsupporting

confidence: 89%

“…Nevertheless, this information provides additional support for a relationship between host genetics and HCV viral clearance and is consistent with several recent reports that evaluated gene expression and gene polymorphisms in individuals with and without sustained virological response to interferon-based regimens (49)(50)(51)(52)(53)(54). Using microarrays in hepatic tissue, Chen and colleagues identified a number of interferon-sensitive genes that correlated with response to antiviral therapy (50).…”

Section: Discussionsupporting

confidence: 80%

Hemophilic Siblings With Chronic Hepatitis C: Familial Aggregation of Spontaneous and Treatment-Related Viral Clearance

Fried

¹

,

Kröner

²

,

Preiss

³

et al. 2006

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“…Interferon-sensitive gene 15 (ISG15) and ubiquitin-specific protease 18 (USP18), which are linked biochemically in IFN-regulatory pathway, modulate the IFN responses against HCV [216]. USP18 up-regulation is one of the factors predicting a lack of response to IFN treatment [217].…”

Section: Role Of Immune Responses In Outcome Following Ifn and Ribavimentioning

confidence: 99%

Immune responses during acute and chronic infection with hepatitis C virus

Ishii

¹

,

Koziel

²

2008

Clinical Immunology

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Hepatitis C virus (HCV) induces persistent infection and causes chronic liver disease in most infected patients. Vigorous HCV-specific CD4+ and CD8+ T cell responses against HCV multiple epitopes are necessary for spontaneous viral clearance during the acute phase, but the virus appears to have multiple strategies to evade these defenses. There are relatively few studies on the role of immune responses during the chronic phase of infection. CD4+ T cell responses appear to protect against liver injury and may be important to clearance during interferon and ribavirin based therapy. Classic cytotoxic T cells (CTL) may primarily damage the liver in chronic HCV, but there may be subpopulations of T cells that protect against liver inflammation. Resolution of these outstanding questions is important to the development of a prophylactic vaccine as well as improving therapeutic options for those with chronic infection.

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“…Data from microarray or other gene expression studies have highlighted the importance of ISGs as well as genes of the interferon signaling pathway (IPGs) in the host response to HCV infection [7][8][9][10][11]. Furthermore, association studies have suggested that polymorphisms in these genes may play a role in differential drug response [12,13].…”

Section: Introductionmentioning

confidence: 99%