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Different response to anti-HCV treatment may be related to immunological gene expression profile in chronically HCV-infected patients

Abstract number: R2487

Almeida A., Caetano J., Santos P., Martinho A., Paiva A., Valente C., Pais B., Luxo C.

Objectives: Hepatitis C virus (HCV) is estimated to infect approximately 170 million people worldwide, being the leading cause of chronic liver diseases in many countries. Without an effective vaccine for HCV, our weapons in the fight against HCV infection are limited to antiviral treatments. Combination therapy with pegylated interferon alpha (peg INF-alpha) and ribavirin is currently the standard treatment for patients with chronic hepatitis C however, this treatment is still limited by a high non-response rate. The mechanism by which peg INF-alpha and ribavirin therapy induces resolution of chronic HCV infection is not fully understood. As immunological mechanisms behind response differences still not completely known, we approached to immunological gene expression profile of chronically HCV-infected patients. Gene expression was accessed in eight chronically HCV-infected patients (four responder and four non-responder patients) during peg IFN-alpha and ribavirin treatment.

Methods: Peripheral blood mononuclear cells were collected before treatment, and one month after starting therapy. RNA isolated from PBMC, was reverse transcribed and gene expression relative quantification was performed by real-time PCR, responders vs non-responders patients.

Results: Our results show differences in various genes expression levels between responders and non-responders patients in pre-treatment and one month after starting therapy. In pre-treatment we observed Increments (1–2 logs) on IL-12p40, IL-2, IL-5, IL-8, FAS, FASL, HLADRB1, GZMB, MADH3 and a lower expression of IL6, IL-17, IL-18, CD4 in responders vs non-responders patients. One month after starting therapy we observed a higher expression of IL-3, IL-6, IL-18, CD4, C3, CCR4, cox-2, HLA-DRB1, IKB2, MADH3 and a lower expression of IL-10, IL-12p35, IP-10, ITAC, MCP-1, MIP-1a in responders vs non-responders patients.

Conclusions: These results point out that response to therapy may be related to differences in expression of genes involved in effectors mechanisms of viral elimination, suggesting potential markers for future approaches. Further prospective large studies are needed to confirm these observations.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Barcelona, Spain
Presentation type:
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