Protein-S-100-beta is increased in patients with decompensated cirrhosis admitted to ICU

Background Hepatic encephalopathy(HE)is highly prevalent in patients with liver diseases.The pathophysiology of HE is centered on the synergic role of hyperammonemia and systemic inflammation.However,some data suggest altered functioning of the blood–brain barrier(BBB).Assessing BBB function is challenging in clinical practice and at the bedside.Protein-S-100 Beta(PS100-Beta)could be a useful peripheral marker of BBB permeability in HE.This study aimed to assess plasmatic PS100-Beta levels in a prospective cohort of patients admitted to the intensive care unit(ICU)with decompensated cirrhosis with and without overt HE.Methods We retrospectively evaluated a prospective cohort of cirrhotic patients admitted to the ICU from October 2013 to September 2015 that had an available plasmatic PS100-Beta measurement.Patients with previous neurological impairment or limitation of intensive or resuscitative measures were excluded.Overt HE was defined as West-Haven grades 2 to 4.The patients were compared to a control cohort of outpatient clinic cirrhotic and non-cirrhotic patients explored for isolated elevation of liver enzymes.After ICU discharge,the patients were followed for at least 3 months for the occurrence of overt HE.Adverse outcomes(liver transplantation or death)were collected.The ability of PS100-Beta–in combination with other factors–to predict overt HE was evaluated in a multivariate analysis using logistic regression.Likelihood ratios were used to determine the effects and calculate odds ratios(OR).Survival analysis was performed by using the Kaplan–Meier method and survival between groups was compared using a Log-rank test.Results A total of 194 ICU patients and 207 outpatients were included in the study.Increased levels of plasmatic PS100-Beta were detected in the ICU decompensated cirrhotic patients compared with the outpatients([0.15±0.01]mg/L vs.[0.08±0]mg/L,P<0.001).ICU patients with overt HE had higher levels of PS100-Beta([0.19±0.03]mg/L)compared with the ICU patients without overt HE([0.13±0.01]mg/L)(P=0.003).PS100-Beta levels did not differ in outpatients with F 0–3 compared to F 4 fibrosis(P=0.670).PS100-Beta values were correlated with Child-Pugh score(P<0.001),Model for End-Stage Liver Disease(MELD)score(P=0.004),C-reactive protein(P<0.001),ammonemia(P<0.001),and chronic liver failure consortium(CLIF-C)organ failure(P<0.001)and CLIF-C acute-on-chronic(P=0.038)scores,but not with leukocytes(P=0.053),procalcitonin(PCT)(P=0.107),or the lymphocyte-to-neutrophil ratio in ICU patients(P=0.522).In a multivariate model including age,ammonemia,PS100-Beta,PCT,MELD,presence of transjugular portosystemic shunt,and sodium level,the diagnostic performance was 0.765 for the diagnosis of overt HE.Patients with a PS100-Beta level<0.12 mg/L had a better overall survival(P=0.019)and a better survival without liver transplantation(P=0.013).Conclusions Serum levels of PS100-Beta are elevated in ICU patients with decompensated cirrhosis,and even more so in those displaying overt HE,and the levels are correlated with outcome.This suggests an increase in the permeability of the BBB in these patients.

肝硬化静脉曲张出血

静脉曲张出血是肝硬化患者死亡的一个主要原因。对于其急性期的处理及二级预防都已明确。最近的2015 Baveno VI专家共识认为,肝硬化静脉曲张出血应作为一个急症,在肝脏或普通ICU中接受治疗。其治疗策略包括早期应用血管活性药物(内镜治疗前)、预防性抗生素及限制性输血方案(目标血红蛋白是7 g/dL)。内镜治疗主要是血管结扎术,而硬化疗法已被摒弃。对于一些严重的肝病患者(Child Pugh C级或初始内镜治疗时发现活动性出血的Child Pugh B级),应在入院后72 h内行经颈静脉肝内门体分流术(TIPS),以降低再出血的风险。二级预防主要是联合应用非选择性β受体阻滞剂(NSBBs)和重复的血管结扎术。当无法耐受NSBBs二级预防、或尽管很好地接受了二级预防但仍然发生再次出血时,抑或是对于顽固性出血,应考虑行TIPS。而当TIPS无法控制出血或对于肝功能已严重恶化的病例,可考虑肝移植。