PNPLA3 Variant and Portal/periportal Histological Pattern in Patients with Biopsy-proven Non-alcoholic Fatty Liver Disease: a Possible Role for Oxidative Stress

Overview

Journal Sci Rep

Specialty Science

Date 2017 Nov 19

PMID 29150621

Citations 33

Authors

Guido Carpino

Daniele Pastori

Francesco Baratta

Diletta Overi

Giancarlo Labbadia

Licia Polimeni

Alessia Di Costanzo

Gaetano Pannitteri

Roberto Carnevale

Maria Del Ben

Marcello Arca

Francesco Violi

Francesco Angelico

Eugenio Gaudio

Affiliations

Soon will be listed here.

Abstract

Pathogenesis of non-alcoholic fatty liver disease (NAFLD) is influenced by predisposing genetic variations, dysmetabolism, systemic oxidative stress, and local cellular and molecular cross-talks. Patatin-like phospholipase domain containing 3 (PNPLA3) gene I148M variant is a known determinant of NAFLD. Aims were to evaluate whether PNPLA3 I148M variant was associated with a specific histological pattern, hepatic stem/progenitor cell (HpSC) niche activation and serum oxidative stress markers. Liver biopsies were obtained from 54 NAFLD patients. The activation of HpSC compartment was evaluated by the extension of ductular reaction (DR); hepatic stellate cells, myofibroblasts (MFs), and macrophages were evaluated by immunohistochemistry. Systemic oxidative stress was assessed measuring serum levels of soluble NOX2-derived peptide (sNOX2-dp) and 8-isoprostaglandin F (8-iso-PGF). PNPLA3 carriers showed higher steatosis, portal inflammation and HpSC niche activation compared to wild-type patients. DR was correlated with NAFLD activity score (NAS) and fibrosis score. Serum 8-iso-PGF were significantly higher in I148M carriers compared to non-carriers and were correlated with DR and portal inflammation. sNox2-dp was correlated with NAS and with HpSC niche activation. In conclusion, NAFLD patients carrying PNPLA3 I148M are characterized by a prominent activation of HpSC niche which is associated with a more aggressive histological pattern (portal fibrogenesis) and increased oxidative stress.

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