IFN-λ3, not IFN-λ4, likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis.

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.

FibroGENE: A gene-based model for staging liver fibrosis.

Background & Aims: The extent of liver fibrosis predicts long-term outcomes, and hence impacts management and therapy. We developed a non-invasive algorithm to stage fibrosis using non-parametric, machine learning methods designed for predictive modeling, and incorporated an invariant genetic marker of liver fibrosis risk.

Methods: Of 4277 patients with chronic liver disease, 1992 with chronic hepatitis C (derivation cohort) were analyzed to develop the model, and subsequently validated in an independent cohort of 1242 patients.