Prognostic power of dynamic enhancement in advanced chronic liver disease: Moving beyond static liver structure

Abstract

The recent study by Stanciu et al, published in World Journal of Hepatology, highlights an important transition in hepatology, shifting from structural assessment toward functional evaluation in advanced chronic liver disease. Their work demonstrates that quantitative hepatic enhancement on gadoxetate-enhanced magnetic resonance imaging (MRI), specifically within Segment VI, provides clinically relevant prognostic information for mortality and decompensation. This editorial evaluates the clinical utility of hepatic enhancement and the semi-quantitative Functional Liver Imaging Score, which integrates hepatocyte uptake via organic anion-transporting polypeptides, biliary excretion mediated by multidrug resistance associated protein 2, and portal hemodynamics. While MRI-derived metrics offer powerful risk stratification, their widespread implementation is often hindered by high costs, inter-scanner variability, and renal contraindications. Conversely, dynamic contrast-enhanced ultrasound provides a cost-effective alternative for real-time hemodynamic profiling, specifically through metrics like hepatic vein arrival time. We propose a tiered diagnostic hierarchy where simpler non-invasive tests and contrast-enhanced ultrasound serve as broad screening tools, reserving advanced functional MRI for high-risk patients. Such a stratified approach facilitates broader access to precision medicine approaches by bridging the gap between sophisticated scientific metrics and scalable clinical practice. Integrating artificial intelligence-driven quantification and rapid protocols will be essential to achieving a truly function-guided management strategy in patients suffering from advanced chronic liver disease.

Key Words: Advanced chronic liver disease; Functional liver imaging score; Hepatic enhancement; Gadoxetate-enhanced magnetic resonance imaging; Contrast-enhanced ultrasound; Hepatic vein arrival time; Portal hypertension; Risk stratification; Prognosis

Core Tip: Current approaches in hepatology increasingly emphasize functional assessment in addition to structural evaluation. While magnetic resonance imaging-derived scores, such as the functional liver imaging score, offer relevant prognostic information, their practical limitations, including cost and technical variability, may restrict widespread use. In contrast, contrast-enhanced ultrasound offers a widely accessible technique for dynamic hemodynamic assessment. The future of clinical practice lies in a stepwise diagnostic approach – utilizing simpler bedside tests for broad screening while reserving advanced magnetic resonance imaging for high-risk cases to support broader implementation of personalized liver care.

This editorial refers to "Hepatic enhancement and signal intensity analysis on magnetic resonance imaging as prognostic biomarkers in advanced chronic liver disease" by Stanciu et al, 2025; https://dx.doi.org/10.4254/wjh.v17.i12.111418.

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INTRODUCTION

The management of chronic liver disease is progressively evolving, shifting from traditional structural evaluations toward a nuanced analysis of hepatic function. Within this evolving landscape, the research conducted by Stanciu et al[1], published in World Journal of Hepatology, supports the prognostic relevance of quantitative hepatic enhancement (HE) via contrast-enhanced magnetic resonance imaging (MRI). In patients with advanced chronic liver disease (ACLD), HE acts as a functional indicator, correlating strongly with established clinical scoring systems while providing independent predictive value for mortality[2]. Crucially, Stanciu et al[1] identified that HE within Segment VI possesses the highest prognostic utility, reflecting the regional interplay between hepatocellular health and microvascular integrity. By quantifying parenchymal changes, this metric extends evaluation beyond structural assessment, offering an objective measure of the progressive distortion of sinusoidal vasculature and reduced portal inflow. This shift necessitates a broader evaluation of how MRI-derived functional biomarkers can be integrated into routine clinical decision-making.

MRI FUNCTIONAL LIVER IMAGING SCORE: EVALUATION OF PROGNOSTIC UTILITY

The Functional Liver Imaging Score (FLIS) represents a strategic advancement in the visual assessment of hepatocellular reserve. As the semi-quantitative imaging tool, the FLIS summarizes hepatocellular function into a clinically usable score by consolidating liver physiology into a composite score ranging from 0 to 6[2]. This score is derived from three distinct physiological pillars: Hepatocellular uptake of contrast media via organic anion-transporting polypeptides, subsequent biliary excretion mediated through the transporter multidrug resistance associated protein 2, and the hemodynamic status of the portal vein[3]. The clinical implications are significant; a high FLIS (5-6) indicates preserved functional competence, whereas a low FLIS (0-2) serves as an indicative of impaired hepatocellular function and significant portal hypertension. Studies indicate that a low FLIS is an independent predictor of post-hepatectomy liver failure and diminished overall survival[4-8].

Despite its robust prognostic utility, the widespread adoption of FLIS is tempered by inherent limitations. First, its semi-quantitative nature introduces reader dependency and subjectivity. Second, the protocol is contingent upon hepatobiliary contrast agents, which are more expensive than standard media and carry specific contraindications, such as severe renal impairment. Furthermore, inter-scanner and inter-manufacturer variability across different field strengths remain significant technical hurdles to standardization[6-8]. These constraints highlight the need for “real-time” alternatives that can assess microvascular changes without the high overhead of advanced MRI.

DYNAMIC CONTRAST-ENHANCED ULTRASOUND: REAL-TIME HEMODYNAMIC PROFILING

Dynamic contrast-enhanced ultrasound (CEUS) represents a practical alternative by providing real-time, bedside assessment of hepatic hemodynamics. Unlike the static phases of other modalities, CEUS allows for the second-by-second visualization of the vascular shunts and flow alterations that characterize ACLD[9,10]. A key parameter in this context is hepatic vein arrival time, which has been validated as a reliable indicator of disease severity[10-14]. Previous studies have shown that the hepatic vein arrival time threshold of approximately 17 seconds can identify cirrhosis with high diagnostic accuracy[15-17].

The strategic value of CEUS lies in its ability to enable broader clinical use; it is a rapid, portable, and low-cost examination providing immediate physiological feedback[18]. Furthermore, a recent study has highlighted the potential of spleen-specific CEUS parameters to non-invasively estimate the hepatic venous pressure gradient, thereby providing insight into the severity of portal hypertension[19]. While CEUS lacks the hepatocyte-specific phase provided by gadoxetate-enhanced MRI, its strength in characterizing microvascular dynamics makes it a synergistic component of a multiparametric diagnostic approach (Table 1)[1,2,4,6,8,10,15,18-21].

Table 1 Comparative strategic utility of magnetic resonance imaging-functional liver imaging score vs contrast-enhanced ultrasound.

Modality	Parameter	Strategic strength	Clinical constraint
MRI-Functional Liver Imaging Score	Uptake (organic anion-transporting polypeptides), excretion (multidrug resistance associated protein 2), and portal flow	Comprehensive assessment of cellular health and reserve[2,4,21]	High cost; inter-scanner variability; renal contraindications[6,8]
MRI-hepatic enhancement	Segment VI quantitative signal intensity	Objective and continuous metric; strong mortality predictor[1]	Logistical complexity; manual regions of interest placement; single-center limits[1]
Contrast-enhanced ultrasound	Hepatic vein arrival time and transit times	Real-time microvascular profiling; bedside-ready; low cost[10,15,18]	Operator-dependent; no hepatocyte-specific phase[19,20]

MRI: Magnetic resonance imaging.

SYNTHESIS: A STRATIFIED DIAGNOSTIC PATHWAY

The transition toward precision hepatology requires a stepwise integration of non-invasive tests. While Stanciu et al[1] successfully objectified functional assessment through quantitative HE in Segment VI, the study's clinical scalability is currently limited by its single-center design and manual placement of regions of interest. To bridge this gap, a tiered diagnostic hierarchy – aligned with Baveno VII and EASL guidelines – is essential[22,23]. In this model, initial screening with blood-based scores and liver stiffness measurements identifies at-risk populations. CEUS can then be utilized for real-time hemodynamic profiling, leveraging its temporal resolution against the spatial depth of MRI. Functional MRI then serves as the “comprehensive assessment tool” for high-risk patients requiring definitive assessment for transplantation or major resection[24-27].

CONCLUSION

The important objective in modern hepatology is the rational integration of advanced functional imaging into scalable clinical workflows. While Stanciu et al[1] have demonstrated the potent prognostic power of quantitative MRI-derived metrics, the path to universal application relies on the development of rapid, abbreviated protocols and artificial intelligence-driven automated quantification. By utilizing a stratified approach – leveraging the accessibility of CEUS for hemodynamic screening[19,20,28,29] and the depth of functional MRI for cellular reserve – clinicians can achieve more individualized patient management. The ultimate goal is to complement structural assessment with functional evaluation and embrace a dynamic, functional understanding of ACLD[30-34].