Impact of small intestinal bacterial overgrowth on systemic inflammation, circulatory and renal function, and liver fibrosis in patients with cirrhosis and ascites.

Background: Small intestinal bacterial overgrowth (SIBO) occurs frequently in patients with cirrhosis, particularly in those with ascites, and promotes the translocation of gut-derived bacterial products into the portal and systemic circulation. We investigated the effects of SIBO on systemic inflammatory activity, circulatory and renal function, and the degree of liver fibrosis in patients with cirrhosis and ascites. Methods: Eighty patients with cirrhosis and ascites were prospectively enrolled. SIBO was determined by lactulose breath test. Serum levels of lipopolysaccharide-binding protein (LBP), tumor necrosis factor-α, and interleukin-6, mean arterial pressure (MAP), cardiac output (CO) by echocardiography, systemic vascular resistance (SVR) as MAP/CO ratio, plasma renin activity (PRA), plasma aldosterone, radioisotope-assessed glomerular filtration rate (GFR), and liver stiffness by shear wave elastography were evaluated. Results: SIBO was detected in 58 patients (72.5%). Compared to patients without SIBO, those diagnosed with SIBO had significantly higher LBP levels (P<0.001), significantly lower MAP (P<0.001) and SVR (P<0.001), and significantly higher CO (P=0.002) and PRA (P<0.001). Patients with SIBO had significantly lower GFR (P=0.02) and higher liver stiffness (P=0.04) compared to those without SIBO. The presence of SIBO was independently associated with LBP (P=0.007) and PRA (P=0.01). Among patients with SIBO, peak breath hydrogen concentration was significantly correlated with serum LBP (P<0.001), MAP (P<0.001), CO (P=0.008), SVR (P=0.001), PRA (P=0.005), plasma aldosterone (P<0.001), GFR (P<0.001), and liver stiffness (P=0.004). Conclusion: SIBO in patients with cirrhosis and ascites may predispose to greater systemic inflammation, circulatory and renal dysfunction, and more advanced liver fibrosis.

Association of left ventricular diastolic dysfunction with inflammatory activity, renal dysfunction, and liver-related mortality in patients with cirrhosis and ascites.

Left ventricular diastolic dysfunction (LVDD) is the predominant cardiac abnormality in cirrhosis. We investigated the association of LVDD with systemic inflammation and its impact on renal function, occurrence of hepatorenal syndrome (HRS) and survival in patients with cirrhosis and ascites. We prospectively enrolled 215 patients with cirrhosis and ascites. We evaluated the diagnosis and grading of LVDD by Doppler echocardiography, inflammatory markers, systemic hemodynamics, vasoactive factors, radioisotope-assessed renal function and blood flow, HRS development and liver-related mortality. LVDD was diagnosed in 142 (66%) patients [grade 2/3: n  = 61 (43%)]. Serum lipopolysaccharide-binding protein (LBP), plasma renin activity (PRA) and glomerular filtration rate (GFR) were independently associated with the presence of grade 2/3 LVDD and the severity of diastolic dysfunction. Serum tumor necrosis factor-α, cardiac output and plasma noradrenaline were also independently associated with the presence of grade 2/3 LVDD. The diastolic function marker E / e ' was strongly correlated with serum LBP ( r  = 0.731; P  < 0.001), PRA ( r  = 0.714; P  < 0.001) and GFR ( r  = -0.609; P  < 0.001) among patients with LVDD. The 5-year risk of HRS development and death was significantly higher in patients with grade 2/3 LVDD compared to those with grade 1 (35.5 vs. 14.4%; P  = 0.01 and 53.3 vs. 28.2%; P  = 0.03, respectively). The occurrence and severity of LVDD in patients with cirrhosis and ascites is closely related to inflammatory activity. Advanced LVDD is associated with baseline circulatory and renal dysfunction, favoring HRS development, and increased mortality.