J.C. Nieto

Effects of intravenous albumin in patients with cirrhosis and episodic hepatic encephalopathy: A randomized double-blind study

BACKGROUND & AIMSnEpisodic hepatic encephalopathy is frequently precipitated by factors that induce circulatory dysfunction, cause oxidative stress-mediated damage or enhance astrocyte swelling. The administration of albumin could modify these factors and improve the outcome of hepatic encephalopathy. The aim of this study is to assess the efficacy of albumin in a multicenter, prospective, double-blind, controlled trial (ClinicalTrials.gov number, NCT00886925).nnnMETHODSnCirrhotic patients with an acute episode of hepatic encephalopathy (grade II-IV) were randomized to receive albumin (1.5g/kg on day 1 and 1.0g/kg on day 3) or isotonic saline, in addition to the usual treatment (laxatives, rifaximin 1200mg per day). The primary end point was the proportion of patients in which encephalopathy was resolved on day 4. The secondary end points included survival, length of hospital stay, and biochemical parameters.nnnRESULTSnFifty-six patients were randomly assigned to albumin (n=26) or saline (n=30) stratified by the severity of HE. Both groups were comparable regarding to demographic data, liver function, and precipitating factors. The percentage of patients without hepatic encephalopathy at day 4 did not differ between both groups (albumin: 57.7% vs. saline: 53.3%; p>0.05). However, significant differences in survival were found at day 90 (albumin: 69.2% vs. saline: 40.0%; p=0.02).nnnCONCLUSIONSnAlbumin does not improve the resolution of hepatic encephalopathy during hospitalization. However, differences in survival after hospitalization suggest that the development of encephalopathy may identify a subgroup of patients with advanced cirrhosis that may benefit from the administration of albumin.

Randomized Pilot Study: Effects of an Exercise Programme and Leucine Supplementation in Patients with Cirrhosis

BackgroundPhysical exercise could improve functional limitations, muscle mass, and health-related quality of life (HRQoL) in patients with cirrhosis.AimThe purpose of this study was to evaluate the efficacy and safety of an exercise programme and leucine supplementation to increase exercise capacity, muscle mass, and HRQoL in patients with cirrhosis.Patients and MethodsSeventeen outpatients with cirrhosis were randomized to an exercise group (nxa0=xa08) or a control group (nxa0=xa09) in a pilot study. The programme of moderate exercise was performed for 12xa0weeks under supervision of a physiotherapist. All patients received oral leucine (10xa0g/day) during the study. At baseline and at the end of the study, we determined exercise capacity (6-min walk and 2-min step tests), anthropometric measurements, and HRQoL by Short Form-36 (SF-36) questionnaire. We also analyzed safety regarding complications of cirrhosis, liver and renal function, inflammatory response and oxidative stress.ResultsIn the exercise group, exercise capacity improved, as shown by the increase in the 6-min walk test from 365 (160–420) to 445xa0m (250–500) (pxa0=xa00.01), and in the 2-min step test (pxa0=xa00.02). Lower thigh circumference also increased, from 41 (34–53) to 46 cm (36–56) (pxa0=xa00.02), and the domains of SF-36 general health (pxa0=xa00.03), vitality (pxa0=xa00.01) and social function (pxa0=xa00.04) improved significantly. In the control group, no statistically significant changes were observed in any of the parameters. We did not observe complications of cirrhosis in either group during the study.ConclusionsA programme of moderate physical exercise together with leucine supplements in patients with cirrhosis is safe and improves exercise capacity, leg muscle mass and HRQoL.

VSL#3 probiotic treatment decreases bacterial translocation in rats with carbon tetrachloride-induced cirrhosis

Probiotics can prevent pathological bacterial translocation in cirrhosis by modulating intestinal microbiota and improving gut barrier and immune disturbances. To evaluate the effect of probiotic VSL#3 on bacterial translocation, intestinal microbiota, gut barrier and inflammatory response in rats with experimental cirrhosis.

Impaired innate immune response of leukocytes from ascitic fluid of patients with spontaneous bacterial peritonitis

An ascitic microenvironment can condition the immune response of cells from cirrhotic patients with spontaneous bacterial peritonitis. To characterize this response, we determined the cytokine concentrations in ascitic fluid and analyzed the phenotype and function of ascitic leukocytes at diagnosis and after antibiotic‐induced resolution in sterile ascites and ascitic fluid of 2 spontaneous bacterial peritonitis variants: positive and negative bacteriological culture. At diagnosis, a high concentration was found of IL‐6 and IL‐10 in the ascitic fluid from negative and positive bacteriological culture. The IL‐6 concentration correlated with the percentage of neutrophils (R = 0.686, P < 0.001). In this context, positive and negative culture neutrophils had an impaired oxidative burst, and, after the antibiotic, the negative culture spontaneous bacterial peritonitis burst was fully recovered. Higher concentrations of IL‐6 and IL‐10 correlated with the presence of low granular CD 14low macrophages (R = −0.436, P = 0.005 and R = 0.414, P = 0.007, respectively). Positive culture spontaneous bacterial peritonitis macrophages expressed the lowest levels of CD16, CD86, CD11b and CD206, and HLA‐DR, suggesting an impaired global function. Treatment increased all markers on the positive culture macrophages and CD11b and CD86 on negative culture macrophages. In negative culture spontaneous bacterial peritonitis, this increase was accompanied by phagocytic function recovery. The antibiotics then reverted the marker levels on positive and negative culture macrophages to the levels on sterile ascitis macrophages and restored ascitic negative culture cell function.

Inverse Association Between Circulating Monocyte-Platelet Complexes and Inflammation in Ulcerative Colitis Patients

BackgroundnCirculating monocytes from active ulcerative colitis (UC) patients produced high levels of tumor necrosis factor-alpha(TNFα) and interleukin(IL)-6 after Toll-like receptors (TLR) stimulation. Since platelets (PLT) can bind to leukocytes, thereby decreasing inflammatory cytokine production, UC patients may exhibit different levels of monocyte-platelet complexes depending on disease activity.nnnMethodsnWe compared among healthy donors, active (onset flare and relapse), and inactive UC patients the presence of circulating monocyte-platelet complexes (CD14+PLT+) and membrane CD162 expression by flow cytometry. Lipopolysaccharide- binding protein, TNFα, and IL-10 were compared by ELISA. Binding of CD14+PLT+ to human umbilical vein endothelial cells (HUVECs) were analyzed by immunofluorescence.nnnResultsnOnset flare UC patients had the lowest levels of CD14+PLT+. Membrane CD162, crucial for the PLT binding, was downregulated only on monocytes from onset flare UC patients. Membrane CD162 expression on CD14+ cells inversely correlated with lipopolysaccharide binding protein levels. As an expected consequence, more CD14+PLT+ than CD14+PLT- from onset flare UC patients bound to activated HUVECs. TNFα tended to negatively correlate with CD14+PLT+ in relapse and inactive UC patients, whereas IL-10 positively correlated with CD14+PLT+ in all UC patients (r = -0.43, P = 0.1 and r = 0.61, P = 0.01, respectively). The anti-inflammatory role of PLT binding to monocytes was confirmed in cocultures of PLT and monocytes. These cocultures increased the percentage of CD14+PLT+ and IL-10 production, and decreased TNFα production. These anti-inflammatory effects were abolished when we blocked the binding of PLT with neutralizing anti-CD62P antibody.nnnConclusionsnDecreased CD162 expression associated with endotoxemia reduced the binding of PLT to monocytes through membrane CD162-CD62P, favoring the inflammatory response of onset flare UC patients.