Assessment of non-alcoholic fatty liver disease (NAFLD) severity with novel serum-based markers: A pilot study.

Atul Goyale,Marta Guerrero Misas,Davide Roccarina,Anjly Jain,Margarita Papatheodoridi,Laura Iogna Prat,Dimitri P Mikhailidis,Emmanuel Tsochatzis,Devaki Nair,Colette Smith,Pavel Strnad

doi:10.1371/journal.pone.0260313

Abstract

Non-alcoholic fatty liver disease (NAFLD) represents a significant public health issue. Identifying patients with simple steatosis from those with non-alcoholic steatohepatitis (NASH) is crucial since NASH is correlated with increased morbidity and mortality. Serum-based markers, including adipokines and cytokines, are important in the pathogenesis and progression of NAFLD. Here we assessed the usefulness of such markers in patients with NAFLD. This prospective, cross-sectional study included 105 adult patients with varying severity of NAFLD. Twelve serum-based markers were measured by 3 biochip platforms and 2 enzyme-linked immunosorbent assay (ELISA) methods. We also developed a NAFLD individual fibrosis index (NIFI) using the serum-based markers mostly correlated with fibrosis severity. Sixty-one out of 105 patients were male (58.1%) with mean age was 53.5 years. Higher Interleukin-6 (IL-6) increased (p = 0.0321) and lower Matrix Metalloproteinase-9 (MMP-9) serum levels (p = 0.0031) were associated with higher fibrosis as measured by Fibroscan® in multivariable regression analysis. Using receiver-operating characteristic (ROC) curve analysis for the NIFI, area under the curve for predicting Fibroscan values ≥ 7.2 kPa was 0.77 (95%CI: 0.67, 0.88, p<0.001), with sensitivity of 89.3%, specificity of 57.9% and a positive likelihood ratio of 2.8. Increasing fibrosis severity in NAFLD is associated with differential expression of IL-6 and MMP-9. NIFI could be valuable for the prediction of advanced NAFLD fibrosis and potentially help avoid unnecessary interventions such as liver biopsy in low-risk patients.

Highlights

Non-alcoholic fatty liver disease (NAFLD) is an increasing health issue with a world-wide prevalence of around 25% [1]
Increasing fibrosis severity in NAFLD is associated with differential expression of IL-6 and Matrix Metalloproteinase-9 (MMP-9)
NAFLD individual fibrosis index (NIFI) could be valuable for the prediction of advanced NAFLD fibrosis and potentially help avoid unnecessary interventions such as liver biopsy in low-risk patients

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) is an increasing health issue with a world-wide prevalence of around 25% [1]. In NAFLD, there is accumulation of fat in the liver (>5%) in the absence of other liver disease (e.g. viral and auto-immune hepatitis), significant alcohol consumption, use of steatogenic medication (e.g. amiodarone, methotrexate or isoniazid), and hereditary disorders [2]. Further ‘hits’ consist of a combination of hormones secreted from adipose tissue, nutritional factors, gut microbiota in-addition to genetic and epigenetic factors that contributed to oxidative stress and inflammation aiding the progression of steatosis to non-alcoholic steatohepatitis (NASH) [4]. Persistent inflammation results in scar tissue formation and progression to fibrosis, which may progress further to liver cirrhosis, with end-stage liver disease and hepatocellular carcinoma being possible outcomes [6]

Objectives

Methods

Results

Conclusion