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THE EFFECT OF VSL#3 ON PORTAL PRESSURE IN COMPENSATED CIRRHOSIS(CC)
P Tandon, K Moncrief, MC Arrieta, RJ Owen, K Rioux, K Madsen, MM Ma
Department of Medicine, University of Alberta, Edmonton, Alberta
BACKGROUND: Portal hypertension (PH) related complications are the cause of significant morbidity and mortality in cirrhotic patients. Decompensated cirrhosis (DC) is defined by the presence of PH complications (ascites, variceal bleeding). Recent literature has supported the role of bacterial translocation (BT) as a primary mediator of splanchnic vasodilation and PH. The detection of gut derived bacteria and bacterial products leads to the release of endotoxin, pro-inflammatory cytokines (interleukin-6 (IL-6), IL-8, tumor necrosis factor-alpha (TNF-alpha)) and nitric oxide (NO). By modifying the intestinal microflora, probiotics have resulted in a reduction in pro-inflammatory cytokines and BT in small studies. The objective of this study was to determine whether VSL#3 (a probiotic combination of 8 strains of Lactobacillus, Bifidobacterium and Streptococcus) would be effective in reducing PH in patients with CC.
METHODS: Patients with CC (absence of active PH complications) and portal hypertension (hepatic venous pressure gradient (HVPG) > 10 mm Hg, received 2 months of VSL#3 (3600 billion bacteria daily). The HVPG, stool microflora, intestinal (stomach, small bowel and colonic) permeability, TNF-alpha, endotoxin, IL-6, IL-8, renin and aldosterone were measured at baseline and study end. Baseline and end of study results were compared using non-parametric analysis.
RESULTS: 10 patients underwent baseline investigations. One patient was excluded due to an HVPG <10 mm Hg. The second was excluded after the development of monoclonal plasma cell rich ascites suggestive of a plasma cell malignancy. The remaining 8 patients had a non-significant reduction in the HVPG (19.7 mm Hg to 18.1 mm Hg). Only 2 patients had impaired baseline small intestinal permeability and therefore not surprisingly, no significant changes in permeability were identified. Although there was no significant change in the plasma renin, the aldosterone level (p=0.03) decreased significantly. The analysis of cytokines and stool microflora analysis are still pending. No adverse events were noted in the study.
CONCLUSIONS: Patients with CC have minimal baseline perturbations in intestinal permeability and neurohormonal markers. Despite this, the improvement in the aldosterone level suggests a possible impact of VSL#3 on the effective circulating volume. It will be important to correlate this with microflora and cytokine changes. The use of VSL#3 should be extended to a study of DC as these patients have more marked baseline dysfunction and therefore may be more likely to experience benefit, including the reduction of portal pressure. As even a 10% reduction in the HVPG is associated with clinical benefit, the need for well-tolerated adjunctive therapies for PH is essential.