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

Abstract

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.

FibroGENE: A gene-based model for staging liver fibrosis

“…Fibrosis progression rate (FPR) was calculated by taking the ratio between the fibrosis stage and the estimated disease duration (in years). Patients were stratified into two groups of stage-constant FPR, according to the median rate (0.076 fibrosis units/year) which was used as a cutoff [16].…”

“…The ILDGC included patients from 20 tertiary and academic centers from 7 countries (Australia, the United Kingdom, Italy, Germany, Spain, Egypt and Hong Kong). The details of the cohort and inclusion criteria have been reported previously [16]. Briefly, for patients with chronic hepatitis C, all consecutive patients who had a liver biopsy before antiviral therapy, with scoring for fibrosis stage and disease activity between 1999 and 2011, were included.…”

“…Based on our recent hypothesis that IFNL genotype is a core variant associated with liver fibrosis independent of disease etiology [16], we tested the validity of the model in 555 patients with chronic hepatitis B (CHB) and 488 with nonalcoholic fatty liver disease (NAFLD). Practice [18].…”

“…We recently reported that single-nucleotide polymorphisms (rs12979860) in the intronic region of the interferon-λ4 (IFNL4) gene modulate liver inflammation and fibrosis, in an etiology independent manner [16]. Thus, it could be hypothesized that this polymorphism, a test for which is widely used and commonly available, might have a role in algorithms that predict fibrosis.…”

Data Mining and Machine Learning Algorithms Using <i>IL28B</i> Genotype and Biochemical Markers Best Predicted Advanced Liver Fibrosis in Chronic Hepatitis C

“…Liver cirrhosis leads to hepatocellular dysfunction, portal hypertension, and the development of hepatocellular carcinoma (HCC) (1,2). Egypt has the highest prevalence of HCV, with genotype 4 (G4) being responsible for over 90 of the cases and the remaining due to genotype 1 (G1) (3).…”