Effects of Albumin Treatment on Systemic and Portal Hemodynamics and Systemic Inflammation in Patients With Decompensated Cirrhosis.

BACKGROUND & AIMS: We investigated the effect of albumin treatment (20% solution) on hypoalbuminemia, cardiocirculatory dysfunction, portal hypertension, and systemic inflammation in patients with decompensated cirrhosis with and without bacterial infections. METHODS: We performed a prospective study to assess the effects of long-term (12 weeks) treatment with low doses (1 g/kg body weight every 2 weeks) and high doses (1.5 g/kg every week) of albumin on serum albumin, plasma renin, cardiocirculatory function, portal pressure, and plasma levels of cytokines, collecting data from 18 patients without bacterial infections (the Pilot-PRECIOSA study). We also assessed the effect of short-term (1 week) treatment with antibiotics alone vs the combination of albumin plus antibiotics (1.5 g/kg on day 1 and 1 g/kg on day 3) on plasma levels of cytokines in biobanked samples from 78 patients with bacterial infections included in a randomized controlled trial (INFECIR-2 study). RESULTS: Circulatory dysfunction and systemic inflammation were extremely unstable in many patients included in the Pilot-PRECIOSA study; these patients had intense and reversible peaks in plasma levels of renin and interleukin 6. Long-term high-dose albumin, but not low-dose albumin, was associated with normalization of serum level of albumin, improved stability of the circulation and left ventricular function, and reduced plasma levels of cytokines (interleukin 6, granulocyte colony-stimulating factor, interleukin 1 receptor antagonist, and vascular endothelial growth factor) without significant changes in portal pressure. The immune-modulatory effects of albumin observed in the Pilot-PRECIOSA study were confirmed in the INFECIR-2 study. In this study, patients given albumin had significant reductions in plasma levels of cytokines. CONCLUSIONS: In an analysis of data from 2 trials (Pilot-PRECIOSA study and INFECIR-2 study), we found that albumin treatment reduced systemic inflammation and cardiocirculatory dysfunction in patients with decompensated cirrhosis. These effects might be responsible for the beneficial effects of albumin therapy on outcomes of patients with decompensated cirrhosis. ClinicalTrials.gov, Numbers: NCT00968695 and NCT03451292.

Effects of Nuclear Factor-E2-related factor 2/Heme Oxygenase 1 on splanchnic hemodynamics in experimental cirrhosis with portal hypertension.

OBJECTIVE: We explored the effects of Nuclear Factor-E2-related factor 2 (Nrf2) and Heme Oxygenase 1 (HO-1) on splanchnic hemodynamics in portal hypertensive rats. METHODS: Experimental cirrhosis with portal hypertension was induced by intraperitoneal injection of carbon tetrachloride. The expression of proteins was examined by immunoblotting. Hemodynamic studies were performed by radioactive microspheres. The vascular perfusion system was used to measure the contractile response of mesentery arterioles in rats. RESULTS: Nrf2 expression in the nucleus and HO-1 expression in cytoplasm was significantly enhanced in portal hypertensive rats. Portal pressure, as well as regional blood flow, increased significantly in portal hypertension and can be blocked by tin protoporphyrin IX. The expression of endogenous nitric oxide synthase and vascular endothelial growth factors increased significantly compared to normal rats, while HO-1 inhibition decreased the expression of these proteins significantly. The contractile response of mesenteric arteries decreased in portal hypertension, but can be partially recovered through tin protoporphyrin IX treatment. CONCLUSIONS: The expression of Nrf2/HO-1 increased in mesenteric arteries of portal hypertensive rats, which was related to oxidative stress. HO-1was involved in increased portal pressure and anomaly splanchnic hemodynamics in portal hypertensive rats.

Splanchnic Hemodynamics and Intestinal Vascularity in Crohn's Disease: An In Vivo Evaluation Using Doppler and Contrast-Enhanced Ultrasound and Biochemical Parameters.

Crohn's disease (CD) is characterized by inflammation and angiogenesis of affected bowel. We evaluated the correlation among vascularity of intestinal wall in CD, splanchnic hemodynamics, clinical activity and biochemical parameters of inflammation and angiogenesis. Sixteen patients with ileal CD and 10 healthy controls were investigated by means of Doppler ultrasound of the superior mesenteric artery and color Doppler and contrast-enhanced ultrasound of the ileal wall. In parallel, serum levels of vascular endothelial growth factor, tumor necrosis factor-α (TNF-α) and nitric oxide, before and 30 min after a standard meal, were evaluated. In CD patients, there was a significant post-prandial reduction in the resistance index and pulsatility index of the superior mesenteric artery, associated with increased levels of nitric oxide and decreased amounts of TNF-α. A correlation was observed between vascular endothelial growth factor and contrast-enhanced ultrasound parameters of intestinal wall vascularity (r = 0.63-0.71, p < 0.05) and between these parameters and superior mesenteric artery blood flow after fasting (resistance and pulsatility indexes: r = -0.64 and -0.72, p < 0.05). Our results revealed a post-prandial increase in nitric oxide and decrease in TNF-α in CD patients in vivo. They also confirm the role of vascular endothelial growth factor in angiogenesis and in pathologic vascular remodeling of CD and its effect on splanchnic blood flow.

Crohn's disease activity assessed by doppler sonography: the role of aortic flow parameters

OBJECTIVES: Intestinal neovascularization and abnormal abdominal arterial flow rates have been reported in Crohn's disease. The aim of this study was to evaluate Doppler sonography as a method for assessing Crohn's disease activity based on changes in splanchnic hemodynamics. METHODS: Forty-eight patients with Crohn's disease, 22 healthy volunteers and 12 patients with irritable bowel syndrome were evaluated by Doppler ultrasound for flow parameters of the aorta and superior mesenteric artery. This evaluation included the cross-sectional area, maximum flow volume, peak systolic velocity, end diastolic velocity, resistance and the pulsatility index. Disease activity was classified according to the Crohn's disease activity index. RESULTS: Most measurements in the aorta and superior mesenteric artery were significantly different between Crohn's disease patients and both control groups. Only the aortic maximum flow volume (CC = 0.37, p = 0.009) and aortic peak systolic velocity (CC = 0.30, p = 0.035) showed a significant positive correlation with the Crohn's disease activity index. The determination of cut-off points for the aortic maximum flow volume and peak systolic velocity measurements increased the sensitivity (80 and 75% for flow volume and velocity, respectively), specificity (57 and 75%), accuracy (67 and 75%) and positive (57 and 68%) and negative (80 and 81%) predictive values. These cut-off values permitted the correct classification of most of the patients with Crohn's disease with respect to disease activity. None of the superior mesenteric artery measurements were able to discriminate patients in relation to disease activity. CONCLUSION: The aortic maximum flow volume and peak systolic velocity levels estimated by Doppler sonography reflected disease activity in Crohn's disease. Doppler sonography of the aorta is therefore a novel noninvasive adjunct method that may be ...

Nonalcoholic fatty liver disease (NAFLD) in nonobese patients with diabetes: Prevalence and relationships with hemodynamic alterations detected with Doppler sonography().

AIM: To evaluate the prevalence, severity, and hemodynamic features of nonalcoholic fatty liver disease (NAFLD) in nonobese diabetics. METHODS: We studied 100 consecutive nonobese (body mass index [BMI] < 30) patients with type 1 (n = 17) or type 2 (n = 83) diabetes and no known causes of liver disease. Steatosis was diagnosed and graded with ultrasonography. Digital sonographic images of the liver and right kidney were analyzed with dedicated software (HDI-Lab), and the liver/kidney ratio of grey-scale intensity was calculated as an index of the severity of the steatosis. Severity scores ranging from 0 (none) to 5 (severe) were compared with sonographic and Doppler findings (right liver size, portal vein diameter and flow velocity, hepatic and splenic arterial pulsatility indices, hepatic-vein flow profile and A- and S-wave velocities). RESULTS: The prevalence of steatosis was 24% in type I and 80% in type II diabetes (grade 1 in 17%, grade 2 in 34%, grade 3 in 33%, grade 4 in 9%, grade 5 in 7%). In patients with steatosis (especially those with grades 4-5 disease), hepatic volume was increased (p < 0.005). Portal vein diameter was increased in grade 5 steatosis. The hepatic artery pulsatility index was significantly increased, particularly in grades 4 and 5 (p < 0.0001); portal and A-wave velocities were significantly reduced in grades 3-5 (p < 0.001); and the hepatic vein flow profile was altered in 27% (biphasic: 20%, flat: 7%) patients with steatosis, although there was no correlation with severity. CONCLUSIONS: NAFLD is very frequent in nonobese diabetics with type 2 but not type 1 disease, and it is associated with hepatomegaly and liver hemodynamic alterations only when it is severe.

Effects of somatostatin analog on splanchnic hemodynamics and plasma glucagon level in portal hypertensive rats.

AIM: To investigate the effects of somatostatin analog on splanchnic hemodynamics and plasma glucagon level in portal hypertensive rats. METHODS: Twenty-eight male Sprague-Dawley rats were equally divided into a intrahepatic portal hypertension (IHPH) model group (n = 14, established by injection of CCl4) and a prehepatic portal hypertension (PHPH) model group (n = 14, established by stenosis of the portal vein). Animals in each group were subdivided into an octreotide treatment (injection) group and a control (normal saline injection) group. Seven age-matched unmodeled/untreated normal rats served as controls. The mean systemic arterial pressure (MSAP) and free portal venous pressure (FPP) were measured. The splanchnic blood flow was detected by injection of toad blood red cell labelled with (51)Cr and (125)I·T3. The concentration of plasma glucagon was determined by radioimmunoassay. RESULTS: All rats with portal hypertension showed significantly decreased splanchnic blood flow and FPP in response to octreotide treatment, as well as markedly increased splanchnic vascular and portal venous resistance. The octreotide treatment did not appear to significantly lower the plasma glucagon levels in either the peripheral or the portal veins. CONCLUSION: Octreotide induces a decrease in splanchnic blood flow in rats with portal hypertension, and this effect results primarily from direct vasoconstriction and to a lesser extent from decreased plasma glucagon level.