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The transforming growth factor- high-producer genotype is associated with response to hepatitis C virus-specific therapy in HIV-positive patients with acute hepatitis C

Nattermann, Jacoba; Vogel, Martina; Nischalke, Hans Dietera; Danta, Markb; Ahlenstiel, Goloa; Michalk, Monikaa; Sauerbruch, Tilmana; Rockstroh, Jürgen Ka; Spengler, Ulricha; for the Kompetenznetz HIV/AIDS

doi: 10.1097/QAD.0b013e3282f85daa
Basic Science: Concise Communications

Background: Coinfection with the hepatitis C virus (HCV) in HIV-positive patients is an emerging health problem. The factors affecting response to HCV-specific therapy are poorly understood but may involve host genetic factors. HCV NS5A-induced inhibition of transforming growth factor-β signaling has been suggested as a potential mechanism involved in HCV pathogenesis. Transforming growth factor-β, a multifunctional cytokine, displays gene polymorphisms (transforming growth factor-β codon 10T/C and codon 25G/C) associated with differential cytokine secretion. Here, we studied whether transforming growth factor-β gene polymorphisms affect treatment response in HCV/HIV coinfection.

Methods: Transforming growth factor-β genotypes were determined in 60 HIV-positive patients with acute hepatitis C treated with pegylated interferon-α. Patients were classified into those with a high-producer genotype and others with non-high-producer genotypes. Rates of sustained virological responses were compared between high-producer and non-high-producer patients. As a control, 100 healthy, 201 HIV(+)/HCV(−), and 148 HCV(+)/HIV(−) subjects were studied.

Results: Transforming growth factor-β genotype distribution did not differ significantly between the groups. In HIV/HCV coinfection carriers of the transforming growth factor-β high-producer genotype had significantly higher sustained virological response rates than patients with a transforming growth factor-β non-high-producer genotype (75 vs. 41.7%; P = 0.039). In a forward-conditional stepwise regression model, transforming growth factor-β high-producer genotype was confirmed as an independent positive predictor for sustained virological response in interferon-α therapy (odds ratio, 4.4; 95% confidence interval, 1.5–13.4; P = 0.009).

Conclusion: Response rates to interferon-α therapy are enhanced in acute HCV-infected HIV-positive patients carrying the transforming growth factor-β ‘high-producer’ genotype. This finding may indicate that a transforming growth factor-β ‘high-producer’ state can partially compensate HCV NS5A-induced inhibition of transforming growth factor-β signaling.

aDepartment of Internal Medicine I, University of Bonn, Bonn, Germany

bFaculty of Medicine UNSW, St Vincent's Clinical School, Sydney, Australia.

Correspondence to J. Nattermann, Department of Internal Medicine I, University of Bonn, Sigmund Freud Straße 25, D-53105 Bonn, Germany. Tel: +49 228 287 15383; fax: +49 228 287 14611; e-mail: jacob.nattermann@ukb.uni-bonn.de

© 2008 Lippincott Williams & Wilkins, Inc.