Dataset Information

Lipopolysaccharide-Induced Neutrophil Dysfunction Following Transjugular Intrahepatic Portosystemic Stent Shunt (TIPSS) Insertion is Associated with Organ Failure and Mortality.

ABSTRACT: Systemic lipopolysaccharide (LPS) is implicated in increasing mortality in patients with alcoholic hepatitis but the underlying mechanisms are not well characterised. The objective of this study was to characterise neutrophil function, LPS and cytokine concentrations within the splanchnic circulation of alcoholic cirrhotic patients undergoing TIPSS insertion for variceal haemorrhage and correlate this with outcome. 26 patients with alcoholic cirrhosis and variceal haemorrhage were studied prior to and 1-hour after TIPSS insertion. Neutrophil function, LPS and cytokine concentrations were determined in arterial, hepatic venous (HV) and portal venous blood (PV). Significantly higher LPS concentrations and neutrophil reactive oxidant species (ROS) production were observed in PV vs HV blood. Cross-incubation of HV plasma with PV neutrophils resulted in reduced ROS production. Insertion of TIPSS was associated with a significant increase in arterial LPS concentrations and deterioration in neutrophil phagocytosis. Number of organ failures and arterial IL-6 concentrations at presentation were associated with increased mortality. The portal circulation has a distinct immunological milieu characterised by a pathological neutrophil phenotype and an anti-inflammatory cytokine profile associated with heightened LPS levels. TIPSS insertion renders this neutrophil functional defect systemic, associated with an increase in arterial LPS and a susceptibility to sepsis.

SUBMITTER: Macnaughtan J

PROVIDER: S-EPMC5209675 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Lipopolysaccharide-Induced Neutrophil Dysfunction Following Transjugular Intrahepatic Portosystemic Stent Shunt (TIPSS) Insertion is Associated with Organ Failure and Mortality.

Macnaughtan Jane J Mookerjee Rajeshwar P RP van der Merwe Schalk S Jalan Rajiv R

Scientific reports 20170104

Systemic lipopolysaccharide (LPS) is implicated in increasing mortality in patients with alcoholic hepatitis but the underlying mechanisms are not well characterised. The objective of this study was to characterise neutrophil function, LPS and cytokine concentrations within the splanchnic circulation of alcoholic cirrhotic patients undergoing TIPSS insertion for variceal haemorrhage and correlate this with outcome. 26 patients with alcoholic cirrhosis and variceal haemorrhage were studied prior ...[more]

PMID: 28051160

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Project description:BACKGROUND: A portosystemic stent shunt may impair cardiac function and haemodynamics. AIMS: To investigate the effects of a transjugular intrahepatic portosystemic shunt (TIPS) on cardiac function and pulmonary and systemic circulation in patients with alcoholic cirrhosis. PATIENTS/METHODS: 17 patients with alcoholic cirrhosis and recent variceal bleeding were evaluated by echocardiography and catheterisation of the splanchnic and pulmonary circulation before and after TIPS. The period of catheter measurement was extended to nine hours in nine of the patients. The portal vein was investigated by Doppler ultrasound before and nine hours after TIPS. RESULTS: Baseline echocardiography showed the left atrial diameter to be slightly increased and the left ventricular volume to be in the upper normal range. Nine hours after TIPS, the left atrial diameter and left ventricular end diastolic volume were increased (by 6% (p<0.01) and 7% (p<0.01) respectively); end systolic volume had not changed significantly. Invasive measurements showed a sharp increase in right atrial pressure (by 101%; p<0.01), mean pulmonary artery pressure (by 92%; p<0.01), pulmonary capillary wedge pressure (by 111%; p<0.01), and cardiac output (8.1 (1.6) to 11.9 (2.4) l/min; p<0.01). Systemic vascular resistance decreased (824 (242) to 600 (265) dyn.s.cm-5 p<0.01), and total pulmonary resistance increased (140 (58.5) to 188 (69.5) dyn.s.cm-5; p<0.05). Total pulmonary resistance (12%; NS), cardiac output (1.4 l/min; p<0. 05), and portal vein blood flow (1.4 l/min; p<0.05) remained elevated for nine hours after TIPS in the subgroup. Portoatrial pressure gradient (43%; p<0.05), portohepatic vascular resistance (72%; p<0.05), and systemic vascular resistance (27%; p<0.01) were consistently reduced. CONCLUSIONS: The increase in the left atrial diameter, the pulmonary capillary wedge pressure, and total pulmonary resistance observed after the TIPS procedure reflected diastolic dysfunction of the hyperdynamic left ventricle in patients with alcoholic cirrhosis. The haemodynamic effects of the portosystemic stent shunt itself on the splanchnic circulation seem to be mainly responsible for the further decrease in systemic vascular resistance. TIPS may unmask a coexisting preclinical cardiomyopathy in patients with alcoholic cirrhosis and portal hypertension.

Project description:Background and aimsTransjugular intrahepatic portosystemic shunt (TIPS) is used for decompressing clinically significant portal hypertension. The aims of this study were to evaluate clinical outcomes and adverse events associated with this procedure.MethodsRetrospective single-center study including 78 patients submitted to TIPS placement between January 2015 and November 2018. Follow-up data were missing in 27 patients, and finally 51 patients were included in the study sample. Data collected from individual registries included demographics, comorbidities, laboratory results, complications, and clinical results according to the indication.ResultsAverage pre-TIPS portosystemic pressure gradient decreased from 18.1 ± 5 to 6 ± 3 mm Hg after TIPS placement. Indications for TIPS were refractory ascites (63%, n = 49), recurrent or uncontrolled variceal bleeding (36%, n = 28), and Budd-Chiari syndrome (1.3%, n = 1). TIPS-related adverse events occurred in 29/51 (56.8%) patients, with hepatic encephalopathy (HE) in 21 (41%) patients, sepsis in 3, liver failure in 2, hemolytic anemia in 1, acute pulmonary edema in 1, and capsular perforation in 1 patient. Mean follow-up was 15.7 ± 15 months. First-month mortality was 11.7% (n = 6) (sepsis, n = 3; acute liver failure, n = 2; and recurrence of variceal bleeding, n = 1) and was significantly higher for patients with Child-Pugh >9 points (p = 0.01), model of end-stage liver disease (MELD) scores >19 (p = 0.02), and for patients with a history of HE before the procedure (p = 0.001). Older age (p = 0.006) and higher levels of creatinine (p = 0.008) were significantly higher in patients developing HE after TIPS. Ascites persisted in 21.2% (7/33 patients) and was more frequent in patients with lower baseline albumin levels (p = 0.003). Recurrent variceal bleeding occurred in 22% (n = 4/18 patients) and was more frequent in patients with lower baseline hemoglobin levels (p = 0.03).ConclusionTIPS is effective in up to 80% of patients presenting with variceal bleeding or refractory ascites. Careful patient selection based on age and HE history may reduce adverse events after TIPS.

Dataset Information

Lipopolysaccharide-Induced Neutrophil Dysfunction Following Transjugular Intrahepatic Portosystemic Stent Shunt (TIPSS) Insertion is Associated with Organ Failure and Mortality.

Publications

Lipopolysaccharide-Induced Neutrophil Dysfunction Following Transjugular Intrahepatic Portosystemic Stent Shunt (TIPSS) Insertion is Associated with Organ Failure and Mortality.

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