Spontaneous bacterial peritonitis associated with experimental cirrhosis: Comparative effect of different therapeutic options on endotoxinemia and hemodynamic derangement

OBJECTIVE:  The aim of this investigation was to assess the role of different therapeutic options aimed at modifying the gut microecology in experimental liver cirrhosis in view of the cytokine cascade and splanchnic and systemic hemodynamics. METHODS:  Cirrhosis was induced in male Sprague-Dawley rats by carbon tetrachloride (CCL4). After the 6th week of CCL4 administration rats were divided into 5 groups for the remaining 6 weeks: (A) saline b.i.d; (B) lactulose 0.5 g b.i.d.; (C) rifaximine 1 mg b.i.d; (D) 2 mL b.i.d of a probiotic mixture and (E) 1 week of rifaximine followed by 5 weeks of probiotic. RESULTS:  Rats with cirrhosis and ascites showed a significantly high concentration of either portal, splanchnic and systemic endotoxin, as well as plasma TNF-α concentration (P < 0.05). Rifaximine alone, rifaximine plus probiotic or probiotic alone significantly decreased the plasma endotoxin concentration at each of the three tested sites, as well as the plasma concentration of TNF-α (P < 0.01). Total Gram-negative aerobic bacteria count in the stool markedly decreased together with a significant increase of the enterococcal population in the rifaximine plus probiotic group and, to a lesser extent, in the other treatment groups. Treated rats showed a significantly decreased occurrence of bacterial peritonitis and the rifaximine plus probiotic treatment was the most effective regimen. Each of the treatments significantly reduced the percentage of positive culture of either mesenteric lymph node or portal vein samples, rifaximine plus probiotic being the most effective. As compared with healthy control rats, those with cirrhosis showed a significantly lower mean arterial pressure and systemic vascular resistance, but a higher cardiac index and portal pressure. Spontaneous bacterial peritonitis further worsened the systemic vascular resistance, but this was partly improved by the rifaximine plus probiotic treatment. CONCLUSION:  These data suggest that the association of a nonabsorbable antibiotic with a probiotic beneficially affects the abnormal systemic vasodilatory response in the course of severe liver cirrhosis, probably through the effects on endotoxin and indirect inhibition of TNF−α release.