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Prognostication in NAFLD: physiological bases, clinical indicators, and newer biomarkers

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Abstract

Non-alcoholic fatty liver disease (NAFLD) is becoming an epidemic in Western countries. Notably, while the majority of NAFLD patients will not evolve until advanced liver disease, a minority of them will progress towards liver-related events. Therefore, risk stratification and prognostication are emerging as fundamental in order to optimize human and economic resources for the care of these patients.

Liver fibrosis has been clearly recognized as the main predictor of poor hepatic and extrahepatic outcomes. However, a prediction based only on the stage of fibrosis is near-sighted and static, as it does not capture the propensity of disease to further progress, the speed of progression and their changes over time. These determinants, which result from the interaction between genetic predisposition and acquired risk factors (obesity, diabetes, etc.), express themselves in disease activity, and can be synthesized by biomarkers of hepatic inflammation and fibrogenesis.

In this review, we present the currently available clinical tools for risk stratification and prognostication in NAFLD specifically with respect to the risk of progression towards hard hepatic outcomes, i.e., liver-related events and death. We also discuss about the genetic and acquired drivers of disease progression, together with the physiopathological bases of their come into action. Finally, we introduce the most promising biomarkers in the direction of repeatedly assessing disease activity over time, mainly in response to future therapeutic interventions.

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  1. Francesca Terracciani and Andrea Falcomatà shared first authorship.

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  1. Hepatology and Clinical Medicine Unit, University Campus Bio-Medico of Rome, Rome, Italy

    Francesca Terracciani, Andrea Falcomatà, Paolo Gallo, Antonio Picardi & Umberto Vespasiani-Gentilucci

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Key points

• The degree of liver fibrosis is the main determinant of prognosis in NAFLD patients.

• At each time point, NAFLD prognosis is affected by disease propensity to progress.

• Genetic determinants and acquired risk factors are key drivers of NAFLD activity.

• Newer biomarkers are expected to help in evaluating speed of progression over time.

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Terracciani, F., Falcomatà, A., Gallo, P. et al. Prognostication in NAFLD: physiological bases, clinical indicators, and newer biomarkers. J Physiol Biochem 79, 851–868 (2023). https://doi.org/10.1007/s13105-022-00934-0

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