Biomarkers in nonalcoholic fatty liver disease

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition characterized by insulin resistance, type 2 diabetes and fat accumulation in the liver that may cause hepatic inflammation and progressive scarring leading to nonalcoholic steatohepatitis (NASH) and irreversible liver damage (cirrhosis). As a result, there has been increased recognition of the need to assess and closely monitor individuals for risk factors of components of NAFLD and NASH, as well as the severity of these conditions using biomarkers.

Aim: To review the biomarkers used to diagnose and define the severity of NAFLD and NASH.

Methods: A comprehensive PubMed and Google Scholar literature search was performed using the terms "non-alcoholic fatty liver disease", "non-alcoholic steatohepatitis", as well as the name of each biomarker known to be used. Articles indexed between 2004 and 2014 were used. Each author read the publications separately and the results were discussed.

Results: Biomarkers offer a potential prognostic or diagnostic indicator for disease manifestation, progression or both. Serum biomarkers, including total cholesterol, triglycerides, insulin resistance and C-peptide, have been used for many years. Emerging biomarkers, such as apolipoprotein A1, apolipoprotein B, leptin, adiponectin, free fatty acids, ghrelin and tumour necrosis factor-alpha, have been proposed as tools that could provide valuable complementary information to that obtained from traditional biomarkers. Moreover, markers of cell death and mitochondrial dysfunction (cytokeratins) represent powerful predictors of risk. For biomarkers to be clinically useful in accurately diagnosing and treating disorders, age-specific reference intervals that account for differences in sex and ethnic origin are a necessity.

Conclusions: The present review attempts to provide a comprehensive analysis of the emerging risk biomarkers of NAFLD and NASH, and to use the clinical significance and analytical considerations of each biomarker pointing out sentinel features of disease progression.

Figures

Figure 1)

Noninvasive biomarkers. Biomarkers can be measured using several technologies including glycomics, proteomics and/or metabolomics, and imaging techniques such as magnetic resonance (MR) and elastography. Pathophysiology: oxidative stress, lipid peroxidation and activity of microbiota can lead to an increase in mitochondrial permeability and caspase activation. At the tissue level, this leads to steatosis, and death by apoptosis and necrosis. An increase in interleukin (IL)-6 and transforming growth factor (TGF)-beta levels leads to transglutamination, which may induce formation of Mallory-Denk bodies in the cells. An increase in TGF-beta, IL8 and RANTES levels result in the recruitment of neutrophils, leading to cellular inflammation. An increase in TGF-beta levels activates stellate cells and leads to collagen secretion as well as a reduction in extracellular matrix degradation. This phenomenon ultimately results in histological fibrosis. FasL Fas ligand; TNF Tumour necrosis factor