IL28B polymorphisms are associated with severity of liver disease in human immunodeficiency virus (HIV) patients coinfected with hepatitis C virus

被引:14
作者
Guzman-Fulgencio, Maria [1 ]
Berenguer, Juan [2 ]
Garcia-Alvarez, Monica [1 ]
Fernandez-Rodriguez, Amanda [1 ]
Jimenez-Sousa, Maria A. [1 ]
Alvarez, Emilio [3 ]
Micheloud, Dariela [4 ]
Carlos Lopez, Juan [2 ]
Miralles, Pilar [2 ]
Cosin, Jaime [2 ]
Catalan, Pilar [5 ]
Resino, Salvador [1 ]
机构
[1] Inst Salud Carlos III, Ctr Nacl Microbiol, Unit HIV Hepatitis Coinfect, Majadahonda 28220, Madrid, Spain
[2] Hosp Gen Gregorio Maranon, Infect Dis HIV Unit, Madrid, Spain
[3] Hosp Gen Gregorio Maranon, Dept Pathol, Madrid, Spain
[4] Hosp Gen Gregorio Maranon, Dept Internal Med, Madrid, Spain
[5] Hosp Gen Gregorio Maranon, Dept Microbiol, Madrid, Spain
关键词
AIDS; Hepatitis C; SNPs; Liver biopsy; Fibrosis; Transaminases; INTERFERON-ALPHA-2B PLUS RIBAVIRIN; FIBROSIS PROGRESSION; GENETIC-VARIATION; INFECTED INDIVIDUALS; INSULIN-RESISTANCE; NATURAL-HISTORY; STEATOSIS; THERAPY; INFLAMMATION; EXPRESSION;
D O I
10.1016/j.jinf.2012.10.025
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Objective: To evaluate the association of IL28B polymorphisms and severity of liver disease among human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients. Methods: We carried out a cross-sectional study on 223 patients. Liver biopsies were evaluated according to Metavir score. IL28B polymorphisms (rs12980275, rs8099917, rs7248668, and rs11881222) were genotyped using GoldenGate (R) assay. Results: IL28B polymorphisms were in strong linkage disequilibrium, especially the couples rs12980275/rs11881222 and rs8099917/rs7248668. For all patients, the rs12980275 A allele increased the odds for significant fibrosis (F >= 2) odds ratio (OR) = 1.68; p = 0.018) and more rapid fibrosis progression (FPR >= 0.075 fibrosis units/year) (OR = 1.64; p = 0.035), and decreased the odds for liver steatosis (OR = 0.61; p = 0.046). Furthermore, the rs8099917 T allele increased the odds for F >= 2 (OR = 1.93; p = 0.020), FPR >= 0.075 (OR = 2.08; p = 0.021), and elevated ALT (>= 80 IU/l) (OR = 1.78; p = 0.048). For HCV-genotype 1 patients, rs12980275 A and rs8099917 T alleles decreased the odds for liver steatosis (OR = 0.22; p < 0.001 and OR = 0.39; p = 0.048; respectively). For HCV-genotype 3 patients, the rs12980275 A allele increased the odds for F >= 2 ((OR = 6.30; p = 0.012), FPR >= 0.075 (OR = 6.40; p = 0.025), and elevated ALT (OR = 4.12; p = 0.037); and the rs8099917 T allele also increased the odds for F >= 2 (OR = 7.56; p = 0.027), FPR >= 0.075 (OR = 50.8; p = 0.012), and elevated ALT (OR = 5.39; p = 0.043). However, we did not find significant trends in patients infected with HCV-genotype 4. Conclusion: The major alleles of IL28B (rs12980275 A, rs11881222 A, rs8099917 T, and rs7248668 G) are associated with increased odds of liver disease severity in HIV patients infected with HCV-genotype 3. In contrast, HCV-genotype 1 patients carrying the major alleles of IL28B polymorphisms had lower odds for liver steatosis. (C) 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:170 / 178
页数:9
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