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Open Access Research article

Meta-analysis: implications of interleukin-28B polymorphisms in spontaneous and treatment-related clearance for patients with hepatitis C

María A Jiménez-Sousa*, Amanda Fernández-Rodríguez, María Guzmán-Fulgencio, Mónica García-Álvarez and Salvador Resino*

Author affiliations

Unit of HIV/Hepatitis Coinfection, National Center for Microbiology, Health Institute Carlos III (ISCIII), 28220 Majadahonda, Madrid, Spain

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Citation and License

BMC Medicine 2013, 11:6  doi:10.1186/1741-7015-11-6

Published: 8 January 2013

Abstract

Background

Since 2009, several studies have identified single-nucleotide polymorphisms (SNPs) near the gene encoding for interleukin (IL)-28 (IL28B) that are strongly associated with spontaneous and treatment-induced hepatitis C virus (HCV) clearance. Because this large amount of data includes some inconsistencies, we consider assessment of the global estimate for each SNP to be essential.

Methods

Relevant studies assessing IL28B polymorphisms associated with sustained virologic response (SVR) and spontaneous clearance (SC) were identified from a literature search of PubMed up to 9 July, 2012. Studies were eligible studies if they included patients infected with HCV or HCV/HIV, or assessed any SNP located within or near the IL28B gene, SVR data available under standard treatment, and/or SC data in patients with acute HCV infection. Pooled odds ratios were estimated by fixed or random effects models when appropriate. Variables such as HCV genotype, ethnicity, and type of co-infection were studied.

Results

Of 282 screened studies, 67 were selected for SVR and 10 for SC. In total, 20,163 patients were studied for SVR and 3,554 for SC. For SVR, we found that all SNPs showed strong associations in patients with HCV genotypes 1 and 4, whereas the pooled ORs were almost three times lower for genotypes 2 and 3 (rs12979860 and rs8099917). Regarding ethnicity, the SNP most associated with SVR was rs12979860 in white patients, whereas in East Asians it seemed to be rs8099917. The most studied SNP (rs12979860) showed similar results for patients co-infected with HCV/HIV, as for those infected with HCV only. Finally, rs12979860 and rs8099917 both appeared to be associated with SC.

Conclusions

IL28B polymorphisms influence both the outcome of interferon treatment and the natural clearance of HCV. However we did not identify a universal predictor SNP, as the best genetic markers differed depending on patient ethnicity, genotype, and type of infection. Nevertheless, our results may be useful for more precise treatment decision-making.

Keywords:
meta-analysis; systematic review; interleukin 28B; HCV; polymorphisms