DNA polymorphisms and response to treatment in patients with chronic hepatitis C: Results from the HALT-C trial

• Published in: Journal of hepatology Vol. 49; no. 4; pp. 548 - 556
• Main Authors: Morgan, Timothy R, Lambrecht, Richard W, Bonkovsky, Herbert L, Chung, Raymond T, Naishadham, Deepa, Sterling, Richard K, Fontana, Robert J, Lee, William M, Ghany, Marc G, Wright, Elizabeth C, O’Brien, Thomas R
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01.10.2008; Elsevier
• Subjects: Adult; Antiviral Agents - therapeutic use; Biological and medical sciences; Chronic/genetics; Drug Therapy, Combination; Female; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; Gene frequency; Genetic; Genotype; Haplotypes; Hepacivirus - genetics; Hepatitis C; Hepatitis C - drug therapy; Hepatitis C - genetics; Human viral diseases; Humans; Infectious diseases; Interferon alpha-2; Interferon-alfa/therapeutic use; Interferon-alpha - therapeutic use; Interleukin-10 - genetics; Male; Medical sciences; Middle Aged; Polyethylene Glycols - therapeutic use; Polymorphism; Polymorphism, Single Nucleotide - genetics; Predictive Value of Tests; Recombinant Proteins; Ribavirin - therapeutic use; Treatment Outcome; Viral diseases; Viral hepatitis; White People - genetics; Genetic; Interferon-alfa/therapeutic use; Gene frequency; Hepatitis C; Chronic/genetics; Polymorphism; Human; Alpha interferon; Hepatic disease; Infection; Chronic; Treatment; Viral disease; DNA; Gastroenterology; Digestive diseases; Genetics; Interferon alfa; Viral hepatitis C
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2008.05.011

Background/Aims Certain host genetic polymorphisms reportedly affect the likelihood of a sustained virological response (SVR) to interferon treatment in subjects infected with hepatitis C virus (HCV). As part of the HALT-C trial we evaluated genetic associations among patients infected with HCV genotype 1 who had failed previous interferon treatment. Methods SVR was determined 24 weeks after completing treatment with pegylated interferon alfa-2a and ribavirin. Eight single nucleotide polymorphisms (SNPs) were selected on the basis of previously reported associations with treatment response. Genotypes were assessed by polymerase chain reaction-based assays. The percentage of patients who achieved SVR was determined for each genotype and for an IL10 promoter diplotype. Results Among 637 non-Hispanic Caucasian patients there were no significant associations between genotype for any individual SNP ( IL10 −1082, IL10 −592, TNF −308, TNF −238, TGFB1 codon 25, CCL2 −2518, EPHX1 codon 113 and AGT −6) and SVR, but SVR was more common among the patients who were homozygous for the ACC IL10 promoter diplotype (adjusted odds ratio, 3.24; 95% confidence interval, 1.33–7.78; p = 0.001). Conclusions Among non-Hispanic Caucasian patients treated with peginterferon and ribavirin after failing previous treatment with interferon, homozygosity for the ACC IL10 promoter diplotype was associated with SVR.