Response to combination therapy with interferon alfa-2a and ribavirin in chronic hepatitis C according to a TNF-alpha promoter polymorphism.
BACKGROUND
Tumor necrosis factor-alpha (TNF-alpha) is involved in the pathogenesis of chronic active hepatitis C. Polymorphisms in the promoter region of the TNF-alpha gene can alter the TNF-alpha expression and modify the host immune response. The present study aimed at the correlation of the G308A TNF-alpha polymorphism with the response to antiviral combination therapy in chronic hepatitis C.


METHODS
62 patients with HCV and 119 healthy unrelated controls were genotyped for the G308A TNF-alpha promoter polymorphism. The patients received 3 x 3 million units of interferon alfa-2a and 1,000-1,200 mg ribavirin daily according to their body weight. A response was defined as absence of HCV-RNA and normalization of S-ALT after 6 months of combination therapy.


RESULTS
With respect to the allele and genotype frequency, a significant difference was not observed between controls and patients with chronic hepatitis C. Furthermore, such a difference was also not observed if responders and non-responders to antiviral therapy were compared.


CONCLUSIONS
The promoter polymorphism of the TNF-alpha gene investigated herein is equally distributed in healthy individuals and patients with hepatitis C and does not seem to predict the response to therapy with interferon alfa-2a and ribavirin.
Schiemann
U
U
Medizinische Klinik, Klinikum der Universität, Innenstadt, Ludwig-Maximilians-Universität München, München, Deutschland. usciema@helios.med.uni-muenchen.de
Glas
J
J
Török
P
P
Simperl
C
C
Martin
K
K
König
A
A
Schmidt
F
F
Schaefer
M
M
Folwaczny
C
C
D000328:Adult; D000483:Alleles; D000998:Antiviral Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D012254:Ribavirin