The INFL3–IFNL4 region (encoding IFNλ3–IFNλ4) has been associated with hepatic inflammation and fibrosis across a spectrum of liver disease, including viral hepatitis and NAFLD, but the exact contributions of IFNλ subclasses in this association was unclear. Eslam et al. now pinpoint IFNλ3 rather than IFNλ4 as the probable mediator of INFL3–IFNL4 haplotype-dependent hepatic inflammation and fibrosis. The researchers examined the phenotypes of a cohort of 1,923 patients with chronic hepatitis C. They observed increased levels of hepatic inflammation, more severe liver fibrosis stage and increased hepatic infiltration of immune cells in individuals with the risk haplotype that produces IFNλ3, rather than IFNλ4. By studying haplotype variants for IFNλ4 (such as those functionally defective or with reduced activity), they found that IFNλ4 activity did not seem to contribute to hepatic inflammation or fibrosis.
Eslam, M. et al. IFN-λ3, not IFN-λ4, likely mediates IFNL3–IFNL4 haplotype-dependent hepatic inflammation and fibrosis. Nat. Genet. 49, 795–800 (2017)
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Ray, K. Deciphering the role of IFNλ subclasses in hepatic inflammation and fibrosis. Nat Rev Gastroenterol Hepatol 14, 326 (2017). https://doi.org/10.1038/nrgastro.2017.63