Letter to the Editor: Beyond the liver - integrating emerging predictors in hepatic encephalopathy after transjugular intrahepatic portosystemic shunt

Abstract

We read with great interest the prospective study by Zhuang et al published in the recent issue of the World Journal of Radiology, regarding the cerebral blood flow changes following transjugular intrahepatic portosystemic shunt creation provides a vital hemodynamic correlate to the pathogenesis of hepatic encephalopathy. However, this letter argues that cerebrovascular alterations should not be interpreted in isolation but rather as the downstream consequence of broader systemic dysregulation. We highlight the critical role of emerging predictors such as sarcopenia, shunt magnitude, and portal vein anatomy, in modulating the neurotoxic burden within the gut-liver-brain axis. By integrating these systemic variables with cerebral hemodynamic metrics, we propose a multidimensional approach to improve risk stratification. This perspective is essential for developing personalized transjugular intrahepatic portosystemic shunt planning strategies that minimize hepatic encephalopathy risk while maintaining shunt efficacy.

Key Words: Hepatic encephalopathy; Transjugular intrahepatic portosystemic shunt; Cerebral blood flow; Sarcopenia; Portal hypertension

Core Tip: While Zhuang et al identify cerebral hypoperfusion as a hallmark of post-transjugular intrahepatic portosystemic shunt encephalopathy, this letter argues that these changes represent the final downstream consequence of a systemic multi-hit failure. We integrate emerging evidence on the gut-liver-muscle axis, emphasizing that sarcopenia, the AMMON-OHE model, and shunt magnitude are critical upstream determinants of neurotoxicity. We propose that to prevent cognitive decline, specialists must move beyond isolated hemodynamic targets and adopt a precision medicine approach, tailoring stent expansion to the patient's individual metabolic and muscular reserve.

TO THE EDITOR

We read with great interest the prospective study by Zhuang et al[1] published in the recent issue of the World Journal of Radiology, regarding the role of cerebral blood flow changes in post-transjugular intrahepatic portosystemic shunt (TIPS) overt hepatic encephalopathy (OHE). The authors identify specific regional hypoperfusion, notably in the fusiform and angular gyri, which provides a crucial hemodynamic fingerprint of the neurological dysfunction associated with this intervention.

Since its inception, TIPS has revolutionized the management of portal hypertension, serving as a critical bridge to transplantation and a definitive treatment for refractory bleeding, yet encephalopathy remains as a critical concern for clinicians[2,3]. In this sense, we must recognize that these cerebrovascular alterations do not occur in a vacuum. They are the downstream consequence of a synergistic failure involving the gut-liver-muscle axis and the hemodynamic properties of the shunt itself[4-6]. In consequence, we should integrate these findings with emerging high-level evidence on systemic and technical predictors to improve patient selection and outcomes.

The pathophysiological cascade begins with the metabolic burden, which determines the neurotoxic threshold the brain must withstand. Recently, Wang et al[7] explores the predictive performance of the AMMON-OHE model, which incorporates age, diabetes, albumin, and venous ammonia, in a TIPS cohort and validate the prognostic relevance between OHE and all-cause mortality, highlighting that systemic metabolic reserve is the primary determinant of neurological resilience.

As demonstrated by Wang et al[7], dynamic ammonia levels and albumin function are superior to traditional liver scores in predicting OHE. This aligns with the gut-muscle hypothesis wherein gut dysbiosis generates the initial toxic load[8], while sarcopenia represents a failure of the body’s primary extrahepatic detoxification buffer[3,9]. Consequently, a sarcopenic patient with high ammonia production will suffer a more severe toxic hit to the blood-brain barrier, likely precipitating the very cerebral blood flow dysregulation and cognitive decline observed by Zhuang et al[1].

Furthermore, we must address stent physiology as a modifiable risk factor that directly influences cerebral hemodynamics. The correlation between shunt dimensions and encephalopathy is critical, yet nuanced[10,11]. While early studies focused on nominal diameter, recent data suggests that the shunt magnitude, defined by the effective flow volume and the degree of portosystemic pressure gradient reduction, is the true driver of neurotoxicity[12,13]. Achieving this balance requires rigorous endovascular assessment of liver hemodynamics, as accurate, reproducible measurement of the portosystemic gradient is foundational to optimizing shunt diameter decisions.

Evidence indicates that controlled expansion using smaller calibers of stent can maintain a delicate balance that is sufficient to decongest the portal system but restrictive enough to limit the flux of neurotoxins reaching the cerebral circulation[14,15]. Therefore, the degree of stent dilation should be tailored to the patient’s sarcopenic status and metabolic risk, such as their AMMON-OHE score, to mitigate the cerebral hypoperfusion risks described by the authors. Additionally, anatomical nuances such as the differential streaming of toxins from the left vs the right portal vein may further modulate the regionality of cerebral impact[16,17].

In conclusion, post-TIPS encephalopathy is a multi-hit phenomenon: The dysbiotic gut loads the gun, the sarcopenic muscle fails to engage the safety, and the high-flow shunt pulls the trigger. We congratulate the authors for elucidating the neurological endpoint of this pathway. To translate these insights into clinical practice, we advocate for a paradigm shift towards a three-step precision approach: (1) Pre-procedural stratification: Mandatory assessment of sarcopenia and metabolic reserve (e.g., AMMON-OHE score) should complement standard liver function tests; (2) Procedural customization: Implementation of controlled expansion strategies specifically for patients with low muscular reserve to limit the neurotoxic flux; and (3) Post-procedural monitoring: Integration of the specific cerebral perfusion markers identified by the authors into surveillance protocols to detect early subclinical encephalopathy before overt cognitive decline occurs.

Ultimately, shifting our clinical focus from isolated hemodynamic targets to an integrative model where the gut, muscle, and shunt are managed as a single functional unit offers the most promising path to reducing the burden of encephalopathy. By adopting this multimodal strategy, we can ensure that the relief of portal hypertension does not come at the cost of the patient's cognitive integrity.

ACKNOWLEDGEMENTS

Lindner C thanks JPM for their continued support in the development of the manuscript.