A randomized, double‐blinded, placebo‐controlled trial analyzing the effect of synbiotics on infectious complications following living donor liver transplant—PREPRO trial

Abstract

Background: Following liver transplantation (LT), bacterial infections occur in over 70% of recipients leading to significant morbidity and mortality. While synbiotics have been reported to decrease infectious complications in various surgical procedures, the evidence of their benefits following LT remains limited. Methods:In this 18-month double-blinded, investigator-initiated, placebocontrolled trial, 100 recipients of live donor liver transplant (LDLT) were randomized to receive either the synbiotic drug Prowel® (Prepro arm) or a placebo, starting 2 days pretransplant and continued for 2 weeks. The primary endpoint was culture-proven bacterial infection in blood, urine or drain fluid within 30 days. Secondary endpoints were hospital stay, noninfectious complications, antibiotic usage and 30-day mortality.Results: Overall infectious complications were significantly lower in the Prepro arm in comparison to the Placebo arm (44% vs 22%, P = .019, OR 0.359; CI: 0.150-0.858). Blood stream infections were significantly less in the study arm (21.7% vs 53.3%, P = .020, OR 0.243; CI: 0.072-0.826), whereas urinary tract and intraabdominal infections were similar. Length of hospital stay, noninfectious complications, deviation from protocol antibiotics and 30-day mortality were comparable. Conclusion:Synbiotics administered for 2 weeks following LDLT significantly reduced overall and blood stream infectious complications in the early postoperative period. However, there was no difference in hospital stay, noninfectious complications, antibiotic usage and mortality.Clinical Trial Registry of India registration number -CTRI/2017/09/009869.

Nutritional Strategies to Manage Malnutrition and Sarcopenia following Liver Transplantation: A Narrative Review

“…The effect of probiotics, prebiotics, or synbiotics on infection after LT was studied in four RCTs [ 84 , 87 , 88 , 89 , 90 ] ( Table 5 ). Mallick et al studied the effect of synbiotics containing Lactobacillus acidophilus, Bifidobacterium longum, Bifidobacterium bifidum, and Bifidobacterium lactis as probiotics and fructooligosaccharide inulin as a prebiotic for 2 weeks after LT [ 89 ]. These synbiotics reduced significantly bloodstream infections in comparison to the placebo [ 89 ].…”

“…Mallick et al studied the effect of synbiotics containing Lactobacillus acidophilus, Bifidobacterium longum, Bifidobacterium bifidum, and Bifidobacterium lactis as probiotics and fructooligosaccharide inulin as a prebiotic for 2 weeks after LT [ 89 ]. These synbiotics reduced significantly bloodstream infections in comparison to the placebo [ 89 ]. Similarly, Zhang et al found that early EN supplemented with synbiotics significantly reduced the incidence of bacterial infections following LT compared to only prebiotics.…”

“…The effects of nutritional interventions on the incidence of infections have been extensively studied in 19 of the 25 included articles. Among these articles, 14 showed beneficial effect on lowering infection, using pre- or probiotics, IMD, and EN [ 46 , 61 , 64 , 65 , 66 , 74 , 75 , 76 , 84 , 87 , 88 , 89 , 90 , 100 ]. Based on our review, we can conclude that nutrition enriched with IMD, EN and pre- and probiotics reduced infections after LT. ESPEN recommends starting EN early after LT together with selected probiotics to reduce infection rates without specifying the type or the dose [ 9 ].…”

“…Dotted lines at the beginning or at the end of the intervention indicates that the duration of the intervention differs between patients in the same study. * Duration varies between participants [ 39 , 40 , 41 , 46 , 51 , 57 , 61 , 64 , 65 , 66 , 67 , 69 , 70 , 71 , 74 , 75 , 76 , 84 , 87 , 88 , 89 , 90 , 91 , 100 , 101 ].…”