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Details

Autor(en) / Beteiligte
Titel
Influence of Interleukin-28B Single-Nucleotide Polymorphisms on Progression to Liver Cirrhosis in Human Immunodeficiency Virus-Hepatitis C Virus-Coinfected Patients Receiving Antiretroviral Therapy
Ist Teil von
  • The Journal of infectious diseases, 2011-06, Vol.203 (11), p.1629-1636
Ort / Verlag
Oxford: Oxford University Press
Erscheinungsjahr
2011
Link zum Volltext
Quelle
Oxford Journals 2020 Medicine
Beschreibungen/Notizen
  • Background. Single-nucleotide polymorphisms (SNPs) near the IL28B gene have recently been associated with spontaneous hepatitis C virus (HCV) clearance and response to interferon-based therapies in patients with chronic hepatitis C. Because human immunodeficiency virus (HIV) coinfection appears to accelerate HCV-related liver fibrosis progression, any influence of IL28B SNP on the risk of developing cirrhosis might be more easily recognized in the coinfected population. Methods. All HIV-HCV-coinfected patients who underwent hepatic elastography before initiating a course of pegylated interferon plus ribavirin therapy at 2 Spanish clinics were retrospectively identified. Liver cirrhosis was defined as > 14.5 kPa by transient elastography. The IL28B rs 12979860 SNP was examined in a blinded fashion. Results. A total of 304 HIV-HCV-coinfected individuals were analyzed (mean age, 43 years; 80% were male; and 85% were receiving antiretroviral therapy), of whom 18% had cirrhosis. IL28B genotype distribution was as follows: CC, 46%; CT, 43%; and TT, 11%. Cirrhosis was more frequent in CC than CT/TT carriers (24% vs 13%; Ñ = .01). Logistic regression analysis revealed that older age (odds ratio [OR], 1.05; 95% confidence interval [CI], 0.99-1.12]; P = .08), past alcohol abuse (OR, 1.97; 95% CI, 0.95-4.06; P = .07), and CC IL28B genotype (OR, 2.32; 95% CI, 1.22-4.41; P = .01) were predictors of cirrhosis. Interestingly, mean (SD) alanine aminotransferase (ALT) levels were greater (90 = 53 vs 71 ± 33 IU/L;, P = .01) in IL28B CC than CT/TT carriers during the prior 4.8 ±3.8 years. Conclusions. The IL28B rs 12979860 CC genotype is associated with a higher prevalence of cirrhosis in HIV-HCV coinfected patients than CT/TT genotypes, suggesting that IL28B CC carriers may experience a more rapid progression of HCV-related liver fibrosis, perhaps as result of increased liver inflammation. Thus, access to HCV treatment is of utmost importance in IL28B CC carriers, in whom treatment response is better and in whom progression to cirrhosis might occur more rapidly.

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