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Modification in CSF specific gravity in acutely decompensated cirrhosis and acute on chronic liver failure independent of encephalopathy, evidences for an early blood-CSF barrier dysfunction in cirrhosis

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Abstract

Although hepatic encephalopathy (HE) on the background of acute on chronic liver failure (ACLF) is associated with high mortality rates, it is unknown whether this is due to increased blood-brain barrier permeability. Specific gravity of cerebrospinal fluid measured by CT is able to estimate blood-cerebrospinal fluid-barrier permeability. This study aimed to assess cerebrospinal fluid specific gravity in acutely decompensated cirrhosis and to compare it in patients with or without ACLF and with or without hepatic encephalopathy. We identified all the patients admitted for acute decompensation of cirrhosis who underwent a brain CT-scan. Those patients could present acute decompensation with or without ACLF. The presence of hepatic encephalopathy was noted. They were compared to a group of stable cirrhotic patients and healthy controls. Quantitative brain CT analysis used the Brainview software that gives the weight, the volume and the specific gravity of each determined brain regions. Results are given as median and interquartile ranges and as relative variation compared to the control/baseline group. 36 patients presented an acute decompensation of cirrhosis. Among them, 25 presented with ACLF and 11 without ACLF; 20 presented with hepatic encephalopathy grade ≥ 2. They were compared to 31 stable cirrhosis patients and 61 healthy controls. Cirrhotic patients had increased cerebrospinal fluid specific gravity (CSF-SG) compared to healthy controls (+0.4 %, p < 0.0001). Cirrhotic patients with ACLF have decreased CSF-SG as compared to cirrhotic patients without ACLF (−0.2 %, p = 0.0030) that remained higher than in healthy controls. The presence of hepatic encephalopathy did not modify CSF-SG (−0.09 %, p = 0.1757). Specific gravity did not differ between different brain regions according to the presence or absence of either ACLF or HE. In patients with acute decompensation of cirrhosis, and those with ACLF, CSF specific gravity is modified compared to both stable cirrhotic patients and healthy controls. This pattern is observed even in the absence of hepatic encephalopathy suggesting that blood-CSF barrier impairment is manifest even in absence of overt hepatic encephalopathy.

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Acknowledgment

The authors gratefully acknowledge the help of Dr. Dominic Yu, Consultant Radiologist at Royal Free Hospital.

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Authors and Affiliations

  1. Brain-Liver Pitié-Salpêtrière Study Group (BLIPS), Hôpital de la Pitié Salpétrière, and INSERM UMR_S 938, CDR Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France

    Nicolas Weiss, Sarah Mouri & Dominique Thabut

  2. Unité de réanimation neurologique, Fédération de Neurologie, Pôle des maladies du système nerveux, Hôpital de la Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France

    Nicolas Weiss

  3. Institut de Neurosciences Translationnelles de Paris, Institut-Hospitalo-Universitaire-A-Institut du Cerveau et de la Moelle (IHU-A-ICM), Paris, France

    Nicolas Weiss

  4. Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, UK

    Matteo Rosselli, Banwari Agarwal & Rajiv Jalan

  5. Soins Intensifs d’Hépatologie, Service d’Hépato-Gastroentérologie, Hôpital de la Pitié Salpétrière, Assistance Publique-Hôpitaux de Paris, Paris, France

    Sarah Mouri & Dominique Thabut

  6. Service de Neuroradiologie, Hôpital de la Pitié-Salpêtrière, Assistance Publique – Hôpitaux de Paris, Paris, France

    Damien Galanaud

  7. Neuro-réanimation chirurgicale, département d’anesthésie-réanimation, Hôpital de la Pitié-Salpêtrière, Assistance Publique – Hôpitaux de Paris, France and Université Pierre et Marie Curie, Paris, France

    Louis Puybasset

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  1. Nicolas Weiss
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  2. Matteo Rosselli
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  3. Sarah Mouri
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  4. Damien Galanaud
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  7. Dominique Thabut
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  8. Rajiv Jalan
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Correspondence to Nicolas Weiss.

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Conflict of interest

Nicolas Weiss declares the following potential conflicts of interest.

Research grant

Eumedica, Gilead.

Speaker fees

Alpha-Wasserman, Norgine, Gore.

Dominique Thabut declares the following potential conflicts of interest. Research grant: Eumedica, Gilead. Speaker fees: Alpha-Wasserman, Norgine, Gore, Gilead, BMS, Janssen.

Rajiv Jalan declares the following potential conflicts of interest. Inventor: Ornithinephenylacetate, a treatment for hepatic encephalopathy; UCL Liver dialysis device. Research grant: Ocera therapeutics, Gambro, Sequana and Grifols. Consultant: Ocera therapeutics, Conatus. Founder: Yaqrit ltd. (UCL spin out). Speaker fees: Grifols, Norgine.

The other authors have nothing to declare.

Additional information

Nicolas Weiss and Matteo Rosselli contributed equally to the work

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Supplemental figure

Specific gravity of different brain regions according to the presence or not of cirrhosis and the presence or not of acute decompensation of cirrhosis. (JPEG 43 kb)

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Weiss, N., Rosselli, M., Mouri, S. et al. Modification in CSF specific gravity in acutely decompensated cirrhosis and acute on chronic liver failure independent of encephalopathy, evidences for an early blood-CSF barrier dysfunction in cirrhosis. Metab Brain Dis 32, 369–376 (2017). https://doi.org/10.1007/s11011-016-9916-9

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  • DOI: https://doi.org/10.1007/s11011-016-9916-9

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