The transjugular intrahepatic portosystemic shunt (TIPS) has been shown to be effective in the control of refractory or recidivant ascites. However, the effect of TIPS on survival as compared with that of large-volume paracentesis plus albumin is uncertain. A multicenter, prospective, clinical trial was performed in 66 patients with cirrhosis and refractory or recidivant ascites (16 Child-Turcotte-Pugh class B and 50 Child-Turcotte-Pugh class C) randomly assigned to treatment with TIPS (n ‫؍‬ 33) or with large-volume paracentesis plus human albumin (n ‫؍‬ 33). The primary endpoint was survival without liver transplantation. Secondary endpoints were treatment failure, rehospitalization, and occurrence of complications. Thirteen patients treated with TIPS and 20 patients treated with paracentesis died during the study period, 4 patients in each group underwent liver transplantation. The probability of survival without transplantation was 77% at 1 year and 59% at 2 years in the TIPS group as compared with 52% and 29% in the paracentesis group (P ‫؍‬ .021). In a multivariate analysis, treatment with paracentesis and higher MELD score showed to independently predict death. Treatment failure was more frequent in patients assigned to paracentesis, whereas severe episodes of hepatic encephalopathy occurred more frequently in patients assigned to TIPS. The number and duration of rehospitalizations were similar in the two groups. In conclusion, compared to large-volume paracentesis plus albumin, TIPS improves survival without liver transplantation in patients with refractory or recidivant ascites. (HEPATOLOGY 2004;40:629 -635.)

Cirrhosis is associated with cardiovascular abnormalities. Scanty information is available as to whether these include left ventricle diastolic dysfunction and wall thickness increase. To this aim in 27 cirrhotic patients with tense ascites, 17 cirrhotic patients with previous episodes of ascites (not actual), and 11 controls we investigated by echocardiography and echocolor Doppler left ventricle diastolic function (E wave, A wave, E/A ratio, deceleration time of E wave), systolic function (ejection fraction), and wall thickness (left ventricle posterior wall thickness + interventricular septum thickness) along with neurohumoral variables. All measurements (supine position) were repeated after total paracentesis (10.7 +/- 0.6 L of ascites) in ascitic patients. Both in patients with and without ascites E/A ratio was reduced as compared with controls (0.93 +/- 0.07 and 0.97 +/- 0.06 vs. 1.18 +/- 0.08, P < .05) while left ventricle wall thickness was increased (18.6 +/- 0.6 and 20.1 +/- 0.8 vs. 17.2 +/- 0.7, P < .05 and P < .01, respectively), irrespective of the postviral or alcoholic cause of liver disease. In all cirrhotics both right and left atrial and right ventricle diameters were significantly greater. Ejection fraction was slightly but significantly (P < .01) reduced in ascitic patients. Paracentesis induced a reduction of the highly increased basal plasma renin activity, aldosterone, norepinephrine (P < .01), and epinephrine (P < .05) and improved diastolic function (E/A, P < .05). Systolic function was unaffected. Thus, irrespective of ascites and cause, advanced cirrhosis is associated with left ventricle diastolic dysfunction and wall thickness increase. We can speculate that neurohumoral overactivity, known to stimulate cardiac tissue growth, may challenge the heart, promoting fibrosis and exerting a further hindrance to ventricular relaxation in patients with cirrhosis experiencing episodes of ascites.

These results provide the first direct evidence that in congestive heart failure chronic ACE inhibitor treatment is accompanied by a marked reduction in central sympathetic outflow. This reduction may depend on a persistent restoration of baroreflex restraint on the sympathetic neural drive.

A prolongation of QT interval has been shown in patients with cirrhosis and it is considered as part of the definition of the so-called 'cirrhotic cardiomyopathy'. The aim of the present study was to assess the determinants of QT interval prolongation in cirrhotic patients. Forty-eight male patients with different stages of liver disease were divided into three subgroups according to the Child-Pugh classification. All patients underwent a 24-h ECG Holter recording. The 24-h mean of QT intervals corrected for heart rate (termed QTc) and the slope of the regression line QT/RR were calculated. HRV (heart rate variability), plasma calcium and potassium concentration and HVPG (hepatic venous pressure gradient) were measured. QTc was progressively prolonged from Child A to Child C patients (P=0.001). A significant correlation between QTc and HVPG was found (P=0.003). Patients with alcohol-related cirrhosis presented QTc prolongation more frequently than patients with post-viral cirrhosis (P<0.001). The QT/RR slope was steeper in subjects with alcoholic aetiology as compared with viral aetiology (P=0.02), suggesting that these patients have a further QTc prolongation when heart rate decreases. The plasma calcium concentration was inversely correlated with QTc (P<0.001). The presence of severe portal hypertension was associated with decreased HRV (P<0.001). Cirrhotic patients with a more severe disease, especially of alcoholic aetiology, who have greater HVPG and lower calcium plasma levels, have an altered ventricular repolarization and a reduced vagal activity to the heart, which may predispose to life-threatening arrhythmias.

The purpose of this study is to characterize synovial fluid- (SF-) derived exosomes of patients with gonarthrosis comparing two methods of isolation and to investigate their immune regulatory properties. Extracellular vesicles (EVs) have been isolated from inflamed SF by polymer precipitation method and quantified by Exocet kit and by nanoparticle tracking analysis. Vesicles expressed all the specific exosomal markers by immunoblot and FACS. After isolation with Exoquick, a relevant contamination by immune complexes was detected, which required further magnetic bead-based purification to remove. SF-derived exosomes significantly stimulated the release of several inflammatory cytokines and chemokines and metalloproteinases by M1 macrophages but did not influence the expression of CD80 and CD86 costimulatory molecules. In conclusion, we characterized purified exosomes isolated from inflamed SF and demonstrate that purified exosomes are functionally active in their ability to stimulate the release of proinflammatory factors from M1 macrophages. Our data indicate that SF-derived exosomes from gonarthrosis patients play a role in disease progression.