Gut Dysbiosis and Hemodynamic Changes as Links of the Pathogenesis of Complications of Cirrhosis

Background. Hemodynamic changes (hyperdynamic circulation) and gut dysbiosis are observed in cirrhosis. It was suggested that gut dysbiosis contributes to the development of hyperdynamic circulation, which aggravates the course of cirrhosis. The aim is to test this hypothesis.Methods. The cross-sectional observational study included 47 patients with cirrhosis. Stool microbiome was assessed using 16S rRNA gene sequencing. Echocardiography with a simultaneous assessment of blood pressure and heart rate was performed. Hemodynamic parameters were calculated. Results. Hyperdynamic circulation was found in 34% of patients. Patients with hyperdynamic circulation had higher incidences of clinically significant ascites (p=0.018), overt hepatic encephalopathy (p=0.042), hypoalbuminemia (p=0.011), hypoprothrombinemia (p=0.019), systemic inflammation (p=0.002), and severe hyperbilirubinemia (p=0.042) than patients without hyperdynamic circulation. The abundance of Proteobacteria (p=0.012), Enterobacteriaceae (p=0.008), Bacilli (p=0.027), Streptococcaceae (p=0.044), Lactobacillaceae (p=0.034), Enterococcaceae (p=0.046), and Fusobacteria (p=0.026) increased and the abundance of Bacteroidetes (p=0.049) and Erysipelotrichia (p=0.029) decreased in the gut microbiome of patients with hyperdynamic circulation compared to patients without hyperdynamic circulation. The systemic vascular resistance value negatively correlated with the abundance of Proteobacteria (r=-0.423; p=0.003), Enterobacteriaceae (r=-0.417; p=0.004), and Fusobacteria (r=-0.401; p=0.005). Heart rate was negatively correlated with the abundance of Bacteroidetes (r=-0.453; p=0.001). The cardiac output value was positively correlated with the abundance of Proteobacteria (r=0.402; p=0.003), Enterobacteriaceae (r=0.424; p=0.003), Fusobacteria (r=0.281; p=0.049), and Bacilli (r=0.314; p=0.031), and negatively correlated with the abundance of Bacteroidetes (r=-0.313; p=0.032) and Erysipelotrichia (r=-0.329; p=0.024). Conclusion. Gut dysbiosis is associated with hyperdynamic circulation, which is associated with a number of complications of cirrhosis.

Electroacupuncture attenuates vascular hyporeactivity in a rat model of portal hypertension induced by bile duct ligation

Background: A hyperdynamic circulation and impaired vascular responsiveness to vasoconstrictors are observed in portal hypertension (PHT) rats. Inflammation is a major contributor to the hyperdynamic circulation state in murine models of PHT. Electroacupuncture (EA) may ameliorate the inflammatory response and limit arterial vasodilatation and portal pressure. This study investigated the possible mechanisms underlying putative hemodynamics effects of EA in normal and PHT rats. Methods: PHT was induced by bile duct ligation (BDL) surgery over 4 weeks in rats. Sham-operated and BDL rats were treated with low-frequency EA (2 Hz) at ST36 10 min three times weekly for one or two consecutive weeks (for a total of 3 or 7 treatments, respectively). Serum tumor necrosis factor-α (TNF-α), nitrite/nitrate (NOx) and 6-keto-prostaglandin F1α (6-keto-PGF1α) were analyzed, and hemodynamic variation and contractile responses to phorbol-12,13-dibutyrate and phenylephrine in aortic and superior mesenteric arterial rings were recorded. Inducible (i) and endothelial (3) nitric oxide synthase (NOS), cyclooxygenase-1 (COX-1), and protein kinase C-α (PKC-α) levels were determined by Western blotting. Results: EA significantly reduced portal pressure and serum TNF-α, NOx and 6-keto-PGF1α levels compared to the untreated BDL group, enhanced maximum contractile responses in the aorta, up-regulated PKC-α, and down-regulated iNOS and COX-1 levels. In addition, EA decreased the aortic angiogenesis signaling cascade, reflected by down-regulation of vascular endothelial growth factor (VEGF) abundance and transforming growth factor β receptor (TGFβR)I/II expression, as assessed by immunostaining. Conclusion: EA attenuates TNF-α, NO and 6-keto-PGF1α overproduction, modulates the vascular levels of constitutive NOS and PKC-α, blunts the development of the angiogenesis cascade, and enhances vascular contractile force in PHT rats.

Gut Dysbiosis and Hemodynamic Changes as Links of the Pathogenesis of Complications of Cirrhosis

Background. Hemodynamic changes (hyperdynamic circulation) and gut dysbiosis are observed in cirrhosis. It was suggested that gut dysbiosis contributes to the development of hyperdynamic circulation, which aggravates the course of cirrhosis. The aim is to test this hypothesis.Methods. The cross-sectional observational study included 47 patients with cirrhosis. Stool microbiome was assessed using 16S rRNA gene sequencing. Echocardiography with a simultaneous assessment of blood pressure and heart rate was performed. Hemodynamic parameters were calculated. Results. Hyperdynamic circulation was found in 34% of patients. Patients with hyperdynamic circulation had higher incidences of clinically significant ascites (p=0.018), overt hepatic encephalopathy (p=0.042), hypoalbuminemia (p=0.011), hypoprothrombinemia (p=0.019), systemic inflammation (p=0.002), and severe hyperbilirubinemia (p=0.042) than patients without hyperdynamic circulation. The abundance of Proteobacteria (p=0.012), Enterobacteriaceae (p=0.008), Bacilli (p=0.027), Streptococcaceae (p=0.044), Lactobacillaceae (p=0.034), Enterococcaceae (p=0.046), and Fusobacteria (p=0.026) increased and the abundance of Bacteroidetes (p=0.049) and Erysipelotrichia (p=0.029) decreased in the gut microbiome of patients with hyperdynamic circulation compared to patients without hyperdynamic circulation. The systemic vascular resistance value negatively correlated with the abundance of Proteobacteria (r=-0.423; p=0.003), Enterobacteriaceae (r=-0.417; p=0.004), and Fusobacteria (r=-0.401; p=0.005). Heart rate was negatively correlated with the abundance of Bacteroidetes (r=-0.453; p=0.001). The cardiac output value was positively correlated with the abundance of Proteobacteria (r=0.402; p=0.003), Enterobacteriaceae (r=0.424; p=0.003), Fusobacteria (r=0.281; p=0.049), and Bacilli (r=0.314; p=0.031), and negatively correlated with the abundance of Bacteroidetes (r=-0.313; p=0.032) and Erysipelotrichia (r=-0.329; p=0.024). Conclusion. Gut dysbiosis is associated with hyperdynamic circulation, which is associated with a number of complications of cirrhosis.

Cardiac Morphology, Function, and Hemodynamics in Patients With Morbid Obesity and Nonalcoholic Steatohepatitis

Background The patients with nonalcoholic fatty liver disease demonstrate an increased cardiovascular risk. The adverse influence of liver abnormalities on cardiac function are among many postulated mechanisms behind this association. The aim of the study was to evaluate cardiac morphology and function in patients with morbid obesity referred for bariatric surgery with liver biopsy. Methods and Results We evaluated with echocardiography 171 consecutive patients without known cardiac disease (median age 42 [interquartile range, 37–48] years, median body mass index 43.7 [interquartile range, 41.0–47.5], 67% female patients. Based on the liver biopsy results, there were 44 patients with nonalcoholic steatohepatitis (NASH), 69 patients with isolated steatosis, and 58 patients without steatosis. Patients with NASH demonstrated signs of left ventricular concentric remodeling and hyperdynamic circulation, including indexed left ventricular end‐diastolic diameter [cm/m 2 ]: NASH 1.87 [0.22]; isolated steatosis 2.03 [0.33]; without steatosis 2.01 [0.19], P =0.001; relative wall thickness: NASH 0.49±0.05, isolated steatosis 0.47±0.06, without steatosis 0.46±0.06, P =0.011; cardiac index [L/m 2 ]: NASH 3.05±0.54, isolated steatosis 2.80±0.44, without steatosis 2.79±0.50, P =0.013. After adjustment for sex, age, blood pressure, and heart rate, most of the measures of the left ventricular systolic and diastolic function, left atrial size, right ventricular function, and right ventricular size did not differ between groups. Conclusions In a group of patients with extreme obesity, NASH was associated with left ventricular concentric remodeling and hyperdynamic circulation. Increased cardiac output in NASH may represent an additional risk factor for incident cardiovascular events in this population.