Noninvasive biomarkers in NAFLD and NASH — current progress and future promise

Abstract

Nonalcoholic fatty liver disease (NAFLD) affects 25% of the global adult population and is the most common chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is the active form of NAFLD, with hepatic necroinflammation and faster fibrosis progression. With an increasing number of patients developing NASH-related end-stage liver disease and pharmacological treatments on the horizon, there is a pressing need to develop NAFLD and NASH biomarkers for prognostication, selection of patients for treatment and monitoring. This requirement is particularly true as liver biopsy utility is limited by its invasive nature, poor patient acceptability and sampling variability. This article reviews current and potential biomarkers for different features of NAFLD, namely, steatosis, necroinflammation and fibrosis. For each biomarker, we evaluate its accuracy, reproducibility, responsiveness, feasibility and limitations. We cover biochemical, imaging and genetic biomarkers and discuss biomarker discovery in the omics era.

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Key points

When assessing a patient with nonalcoholic fatty liver disease (NAFLD), the key histological features of interest include the degree of steatosis, necroinflammation and fibrosis.

MRI-estimated proton density fat fraction is currently the most accurate test to quantify hepatic steatosis and can be considered the gold standard.

Magnetic resonance elastography is the most accurate fibrosis test, yet its use is limited by cost and availability.

Controlled attenuation parameter and liver stiffness measurement by transient elastography also enables simultaneous assessment of hepatic steatosis and fibrosis, albeit with lower accuracy and success rates than MRI-based methods.

Plasma cytokeratin 18 (CK18) fragment levels are a marker of hepatocyte apoptosis and represent the most extensively evaluated biomarker of steatohepatitis, although the accuracy is modest.

A number of gene polymorphisms (such as those in PNPLA3 and TM6SF2) have been shown to correlate with NAFLD and its severity, yet their role in patient assessment remains to be established.