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Interferon-λ rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease

Eslam, M., Hashem, A.M., Leung, R., Romero-Gomez, M., Berg, T., Dore, G.J., Chan, H.L.K., Irving, W.L., Sheridan, D., Abate, M.L., Adams, L.A., Mangia, A., Weltman, M., Bugianesi, E., Spengler, U., Shaker, O., Fischer, J., Mollison, L., Cheng, W., Powell, E., Nattermann, J., Riordan, S., McLeod, D., Armstrong, N.J.ORCID: 0000-0002-4477-293X, Douglas, M.W., Liddle, C., Booth, D.R., George, J., Ahlenstiel, G., Ampuero, J., Bassendine, M., Wong, V.W.S., Rosso, C., White, R., Mezzabotta, L., Suppiah, V., Michalk, M., Malik, B., Matthews, G., Applegate, T., Grebely, J., Fragomeli, V., Jonsson, J.R. and Santaro, R. (2015) Interferon-λ rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease. Nature Communications, 6 . p. 6422.

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Tissue fibrosis is a core pathologic process that contributes to mortality in ~45% of the population and is likely to be influenced by the host genetic architecture. Here we demonstrate, using liver disease as a model, that a single-nucleotide polymorphism (rs12979860) in the intronic region of ​interferon-λ4 (​IFNL4) is a strong predictor of fibrosis in an aetiology-independent manner. In a cohort of 4,172 patients, including 3,129 with chronic hepatitis C (CHC), 555 with chronic hepatitis B (CHB) and 488 with non-alcoholic fatty liver disease (NAFLD), those with rs12979860CC have greater hepatic inflammation and fibrosis. In CHC, those with rs12979860CC also have greater stage-constant and stage-specific fibrosis progression rates (P<0.0001 for all). The impact of rs12979860 genotypes on fibrosis is maximal in young females, especially those with HCV genotype 3. These findings establish rs12979860 genotype as a strong aetiology-independent predictor of tissue inflammation and fibrosis.

Item Type: Journal Article
Publisher: Nature Publishing Group
Copyright: © 2015 Macmillan Publishers Limited.
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