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<p>Ammonia is a product of amino acid metabolism that accumulates in the blood of patients with liver cirrhosis, leading to neurotoxic effects and hepatic encephalopathy (HE). HE manifestations can range from mild, subclinical disturbances in cognition, or minimal HE (mHE) to gross disorientation and coma, a condition referred to as overt HE. Many blood-based biomarkers reflecting these neurotoxic effects of ammonia and liver disease can be measured in the blood allowing the development of new biomarkers to diagnose cirrhosis patients at risk of developing HE. The effect of ammonia on the brain is modulated by severity of systemic inflammation, and both hyperammonemia and inflammation can induce oxidative stress, which may mediate the neurological alterations associated to HE. This review aims to provide the latest evidence on biomarkers of HE beyond ammonia. We present different approaches to predict overt HE based on the combination of blood ammonia with some analytical and clinical parameters. Magnetic resonance analysis of brain images could also provide sensitive diagnostic biomarkers based on neuroimaging parameters. Some reports suggest that markers of systemic inflammation, oxidative stress, and central nervous system-derived components, may serve as additional biomarkers of HE. The involvement of extracellular vesicles and microbiota in the pathophysiology of mHE and HE has recently acquired importance and it would be interesting to explore their usefulness as early biomarkers of the disease. It is important to have a biomarker or a combination of them for early diagnosis of mHE to improve its treatment and prevent progression to overt HE.</p>

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Ammonia and beyond – biomarkers of hepatic encephalopathy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月15日

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  • Juan-José Gallego,
  • María-Pilar Ballester,
  • Alessandra Fiorillo,
  • Franc Casanova-Ferrer,
  • Adrià López-Gramaje,
  • Amparo Urios,
  • Yaiza María Arenas,
  • María-Pilar Ríos,
  • Lucía Durbán,
  • Javier Megías,
  • Teresa San-Miguel,
  • Salvador Benlloch,
  • Paloma Lluch,
  • Rajiv Jalan,
  • Carmina Montoliu

摘要

Ammonia is a product of amino acid metabolism that accumulates in the blood of patients with liver cirrhosis, leading to neurotoxic effects and hepatic encephalopathy (HE). HE manifestations can range from mild, subclinical disturbances in cognition, or minimal HE (mHE) to gross disorientation and coma, a condition referred to as overt HE. Many blood-based biomarkers reflecting these neurotoxic effects of ammonia and liver disease can be measured in the blood allowing the development of new biomarkers to diagnose cirrhosis patients at risk of developing HE. The effect of ammonia on the brain is modulated by severity of systemic inflammation, and both hyperammonemia and inflammation can induce oxidative stress, which may mediate the neurological alterations associated to HE. This review aims to provide the latest evidence on biomarkers of HE beyond ammonia. We present different approaches to predict overt HE based on the combination of blood ammonia with some analytical and clinical parameters. Magnetic resonance analysis of brain images could also provide sensitive diagnostic biomarkers based on neuroimaging parameters. Some reports suggest that markers of systemic inflammation, oxidative stress, and central nervous system-derived components, may serve as additional biomarkers of HE. The involvement of extracellular vesicles and microbiota in the pathophysiology of mHE and HE has recently acquired importance and it would be interesting to explore their usefulness as early biomarkers of the disease. It is important to have a biomarker or a combination of them for early diagnosis of mHE to improve its treatment and prevent progression to overt HE.