RT Journal Article
T1 IFN-λ3, not IFN-λ4, likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis.
A1 Eslam, Mohammed
A1 McLeod, Duncan
A1 Kelaeng, Kebitsaone Simon
A1 Mangia, Alessandra
A1 Berg, Thomas
A1 Thabet, Khaled
A1 Irving, William L
A1 Dore, Gregory J
A1 Sheridan, David
A1 Grønbæk, Henning
A1 Abate, Maria Lorena
A1 Hartmann, Rune
A1 Bugianesi, Elisabetta
A1 Spengler, Ulrich
A1 Rojas, Angela
A1 Booth, David R
A1 Weltman, Martin
A1 Mollison, Lindsay
A1 Cheng, Wendy
A1 Riordan, Stephen
A1 Mahajan, Hema
A1 Fischer, Janett
A1 Nattermann, Jacob
A1 Douglas, Mark W
A1 Liddle, Christopher
A1 Powell, Elizabeth
A1 Romero-Gomez, Manuel
A1 George, Jacob
A1 International Liver Disease Genetics Consortium (ILDGC), 
AB Genetic variation in the IFNL3-IFNL4 (interferon-λ3-interferon-λ4) region is associated with hepatic inflammation and fibrosis. Whether IFN-λ3 or IFN-λ4 protein drives this association is not known. We demonstrate that hepatic inflammation, fibrosis stage, fibrosis progression rate, hepatic infiltration of immune cells, IFN-λ3 expression, and serum sCD163 levels (a marker of activated macrophages) are greater in individuals with the IFNL3-IFNL4 risk haplotype that does not produce IFN-λ4, but produces IFN-λ3. No difference in these features was observed according to genotype at rs117648444, which encodes a substitution at position 70 of the IFN-λ4 protein and reduces IFN-λ4 activity, or between patients encoding functionally defective IFN-λ4 (IFN-λ4-Ser70) and those encoding fully active IFN-λ4-Pro70. The two proposed functional variants (rs368234815 and rs4803217) were not superior to the discovery SNP rs12979860 with respect to liver inflammation or fibrosis phenotype. IFN-λ3 rather than IFN-λ4 likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis.
YR 2017
FD 2017-04-10
LK http://hdl.handle.net/10668/11076
UL http://hdl.handle.net/10668/11076
LA en
DS RISalud
RD Apr 7, 2025