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Review
. 2014 Dec;28(11):607-18.
doi: 10.1155/2014/757929.

Biomarkers in nonalcoholic fatty liver disease

Manuela G Neuman, Lawrence B Cohen, Radu M Nanau
Review

Biomarkers in nonalcoholic fatty liver disease

Manuela G Neuman et al. Can J Gastroenterol Hepatol. 2014 Dec.

Abstract
in English, French

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.

HISTORIQUE :: La stéatose hépatique non alcoolique (SHNA), une maladie hépatique chronique caractérisée par l’insulinorésistance, le diabète de type 2 et l’accumulation de lipides dans le foie, peut être responsable d’une inflammation hépatique et d’une fibrose progressive qui peut entraîner une stéatohépatite non alcoolique (SNA) et une atteinte hépatique irréversible (cirrhose). Par conséquent, on convient de plus en plus de la nécessité d’utiliser des biomarqueurs pour assurer une surveillance étroite des patients. Cette surveillance portera sur les facteurs de risque de divers aspects de la SHNA et de la SNA, ainsi que sur la gravité de ces maladies.

OBJECTIF :: Analyser les biomarqueurs utilisés pour diagnostiquer et définir la gravité de la SHNA et de la SNA.

MÉTHODOLOGIE :: Les auteurs ont effectué une analyse bibliographique approfondie des articles indexés dans PubMed et Google Scholar entre 2004 et 2014 au moyen des termes non-alcoholic fatty liver disease, nonalcoholic steatohepatitis et du nom de chacun des biomarqueurs qu’ils savaient être utilisés. Chaque auteur a lu les publications séparément et ensemble, ils ont discuté des résultats.

RÉSULTATS :: Les biomarqueurs procurent un pronostic potentiel d’indicateurs diagnostiques de manifestations ou d’évolution de la maladie, ou de ces deux problèmes. Les biomarqueurs sériques, y compris le cholestérol total, les triglycérides, l’insulinorésistance et le peptide C, sont utilisés depuis de nombreuses années. Des biomarqueurs émergents, tels que l’apolipoprotéine A1, l’apolipoprotéine B, la leptine, l’adiponectine, les acides gras libres, la ghréline et le facteur de nécrose tumorale alpha, sont des outils susceptibles de fournir de l’information précieuse, qui complétera celle obtenue grâce aux biomarqueurs habituels. De plus, les marqueurs de mort cellulaire et de dysfonction mitochondriale (les cytokératines) sont de puissants prédicteurs de risque. Pour que les biomarqueurs soient utiles sur le plan clinique pour bien diagnostiquer et traiter ces maladies, il faut obtenir des intervalles de référence propres à l’âge qui tiennent compte des différences en fonction du sexe et de l’origine ethnique.

CONCLUSIONS :: La présente analyse visait à effectuer un examen approfondi des biomarqueurs émergents du risque de SHNA et de SNA et à utiliser la signification clinique et les considérations analytiques de chaque biomarqueur qui met en lumière les caractéristiques sentinelles d’une évolution pathologique.

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Figures

Figure 1)
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
See this image and copyright information in PMC

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