title: 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.
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.
authors.affiliation: 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@aphp.fr.|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@aphp.fr.|Institut de Neurosciences Translationnelles de Paris, Institut-Hospitalo-Universitaire-A-Institut du Cerveau et de la Moelle (IHU-A-ICM), Paris, France. nicolas.weiss@aphp.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Weiss
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, UK.
authors.forename: Matteo
authors.initials: M
authors.lastname: Rosselli
authors.affiliation: 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.|Soins Intensifs d'Hépatologie, Service d'Hépato-Gastroentérologie, Hôpital de la Pitié Salpétrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Mouri
authors.affiliation: Service de Neuroradiologie, Hôpital de la Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Galanaud
authors.affiliation: 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.
authors.forename: Louis
authors.initials: L
authors.lastname: Puybasset
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, UK.
authors.forename: Banwari
authors.initials: B
authors.lastname: Agarwal
authors.affiliation: 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.|Soins Intensifs d'Hépatologie, Service d'Hépato-Gastroentérologie, Hôpital de la Pitié Salpétrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Thabut
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, UK.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Jalan
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D000368:Aged; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D001923:Brain Chemistry; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D002908:Chronic Disease; D005260:Female; D006501:Hepatic Encephalopathy / Q000134:cerebrospinal fluid; D006801:Humans; D008103:Liver Cirrhosis / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013046:Specific Gravity; D014057:Tomography, X-Ray Computed
keywords: Blood-brain barrier; Blood-cerebrospinal fluid-barrier; Brain edema; CT scan; Hepatic encephalopathy