Interferon-λ rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease
- Eslam, M
- Hashem, AM
- Leung, R
- Romero-Gomez, M
- Berg, T
- Dore, GJ
- Chan, HLK
- Irving, WL
- Sheridan, D
- Abate, ML
- Adams, LA
- 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, NJ
- Douglas, MW
- Liddle, C
- Booth, DR
- George, J
- Ahlenstiel, G
- Ampuero, J
- Bassendine, M
- Wong, VWS
- Rosso, C
- White, R
- Mezzabotta, L
- Suppiah, V
- Michalk, M
- Malik, B
- Matthews, G
- Applegate, T
- Grebely, J
- Fragomeli, V
- Jonsson, JR
- Santaro, R
DOIAbstract
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...
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