The transforming growth factor-beta high-producer genotype is associated with response to hepatitis C virus-specific therapy in HIV-positive patients with acute hepatitis C.
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-beta signaling has been suggested as a potential mechanism involved in HCV pathogenesis. Transforming growth factor-beta, a multifunctional cytokine, displays gene polymorphisms (transforming growth factor-beta codon 10T/C and codon 25G/C) associated with differential cytokine secretion. Here, we studied whether transforming growth factor-beta gene polymorphisms affect treatment response in HCV/HIV coinfection.


METHODS
Transforming growth factor-beta genotypes were determined in 60 HIV-positive patients with acute hepatitis C treated with pegylated interferon-alpha. 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-beta genotype distribution did not differ significantly between the groups. In HIV/HCV coinfection carriers of the transforming growth factor-beta high-producer genotype had significantly higher sustained virological response rates than patients with a transforming growth factor-beta non-high-producer genotype (75 vs. 41.7%; P = 0.039). In a forward-conditional stepwise regression model, transforming growth factor-beta high-producer genotype was confirmed as an independent positive predictor for sustained virological response in interferon-alpha therapy (odds ratio, 4.4; 95% confidence interval, 1.5-13.4; P = 0.009).


CONCLUSIONS
Response rates to interferon-alpha therapy are enhanced in acute HCV-infected HIV-positive patients carrying the transforming growth factor-beta 'high-producer' genotype. This finding may indicate that a transforming growth factor-beta 'high-producer' state can partially compensate HCV NS5A-induced inhibition of transforming growth factor-beta signaling.
Nattermann
Jacob
J
Department of Internal Medicine I, University of Bonn, Bonn, Germany. jacob.nattermann@ukb.uni-bonn.de
Vogel
Martin
M
Nischalke
Hans Dieter
HD
Danta
Mark
M
Ahlenstiel
Golo
G
Michalk
Monika
M
Sauerbruch
Tilman
T
Rockstroh
Jürgen K
JK
Spengler
Ulrich
U
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006526:Hepatitis C / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008875:Middle Aged; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics*; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D016898:Interferon-alpha; D016212:Transforming Growth Factor beta