Association between PNPLA3[G]/I148M variant, steatosis and fibrosis stage in hepatitis C virus - genetic matters.

There is an established correlation between the PNPLA3 rs738409 C > G single nucleotide polymorphism (SNP) and hepatic steatosis and fibrosis in hepatitis C virus (HCV) infected patients. However not all data is convergent regarding the exact impact of this SNP on the pattern of disease progression in different clinical settings. In this study, we aimed to further bridge the knowledge gap on this topic by investigating the role of the G allele in promoting steatosis, fibrosis and disease progression in relation to other metabolic and anthropometric host factors. Two hundred and fifty consecutive patients, previously diagnosed with chronic hepatitis C (CHC) underwent liver biopsy. Histology was assessed using the Metavir scoring system. Transient elastography was used for follow-up. Ninety-eight patients were genotyped for PNPLA3 rs738409 and followed up for fibrosis progression. PNPLA3 rs738409[G] allele was significantly correlated with severe steatosis (P = 0.04), severe fibrosis at the time of enrollment (P = 0.0005) and fibrosis progression with an OR of 10.31 (95% CI 1.06 - 99.59, P = 0.04), after a mean follow-up time of 62.85 (95%CI: 52.21 - 76.15) months. Severe steatosis at the time of enrollment had an OR of 11.02 (95% CI 1.48 - 82.09, P = 0.01) for the association with fibrosis progression. The HOMA-IR index was also positively correlated with severe fibrosis (P = 0.03) and fibrosis progression on univariate analysis (P = 0.02). PNPLA3 rs738409[G] allele is a reliable predictor for steatosis and fibrosis in CHC. The presence of G allele, along with severe steatosis and insulin resistance are significant predictors for fibrosis progression.

A novel pathophysiological-based panel of biomarkers for the diagnosis of nonalcoholic steatohepatitis.

Non-invasive biochemical markers are useful to distinguish between nonalcoholic steatohepatitis (NASH) and simple steatosis. The aim of this study was to test the diagnostic value of a panel of biomarkers derived from the pathophysiological events involved in the development of NASH. A total of 79 patients: 20 not-NASH and 59 NASH were included in the study. Definitive NASH was defined according to Kleiner's classification. In all subjects, parameters of the metabolic syndrome, insulin resistance (HOMA-IR), adiponectin, interleukin-6 (IL-6) and total cytokeratin-18 (M65 antigen) were determined. Univariate and multivariate analysis were used to identify independent predictors of NASH. In multivariate analysis three markers were independently predictors of NASH: adiponectin, IL-6 and M65 levels. In decreasing order, the independent predictors of NASH (NAS≥5) were M65 with an AUROC of 0.791, IL-6 with an AUROC of 0.727 and adiponectin with an AUROC of 0.709. The combination of two biomarkers yelded an AUROC of 0.828 for M65 and IL-6, 0.841 for adiponectin and M65 and 0.852 for adiponectin and IL-6. The best value was obtained by triple combination: adiponectin, M65 and IL-6 with and AUROC of 0.903, Sp=85.7% (PPV=94.2%) and Se=84.5% (NPV=66.7%). In conclusion, a novel pathophysiological - based panel of biomarkers combining total CK-18, IL-6 and adiponectin may be useful to predict NASH.