Post-hoc analysis of a randomized controlled trial on the impact of pre-transplant use of probiotics on outcomes after liver transplantation

Abstract

Perioperative use of probiotics serves as efficient prophylaxis against postoperative infections after liver transplantation, yet data on long-term effects of pre-transplant probiotic intake is lacking. The aim of this study was to assess the effects of pre-transplant probiotic administration on long-term results of liver transplantation. This was secondary analysis of a randomized trial. Patients were randomized to receive either 4-strain probiotic or placebo before liver transplantation. Five year graft survival was set as the primary end-point. Secondary end-points comprised serum bilirubin and C-reactive protein (CRP) concentration, international normalized ratio (INR), serum transaminases and gamma-glutamyl transferase (GGT) activity. Study group comprised 44 patients, of whom 21 received probiotics and 23 received placebo with 5-year graft survival of 81.0% and 87.0%, respectively (p = 0.591). Patients in the probiotic arm exhibited lower INR (p = 0.001) and CRP (p = 0.030) over the first 6 post-transplant months. In the absence of hepatitis B or C virus infection, pre-transplant administration of probiotics also reduced aspartate transaminase activity (p = 0.032). In the intervention arm, patients receiving probiotics for under and over 30 days had 5-year graft survival rates of 100% and 66.7%, respectively (p = 0.061). Duration of probiotic intake > 30 days was additionally associated with increased INR (p = 0.031), GGT (p = 0.032) and a tendency towards increased bilirubin (p = 0.074) over first 6 post-transplant months. Pre-transplant administration of probiotics has mild positive influence on 6-month allograft function, yet should not exceed 30 days due to potential negative effects on long-term outcomes. (ClinicalTrials.gov Identifier: NCT01735591).

Updated Insights into Probiotics and Hepatobiliary Diseases

“…Patients have a risk of developing a bacterial infection after liver surgery, which may potentially result in liver failure and even mortality [ 91 ]. Numerous evidence illustrates that the perioperative use of probiotics contributes to lower infection rates and efficient prophylaxis against postoperative infections after liver surgery [ 91 , 92 ].…”

“…A secondary analysis of a randomized trial showed that the pretransplant administration of 3 × 10 9 colony-forming unit (CFU) probiotic capsules containing Lactococcus lactis PB411 (50.0%), Lactobacillus casei PB121 (25.0%), Lactobacillus acidophilus PB111 (12.5%), and Bifidobacterium bifidum PB211 (12.5%) had benefits on 6-month allograft function, including a decreased international normalized ratio (INR) for prothrombin time, c-reactive protein (CRP) concentration, and AST activity. However, the intake should not be longer than 30 days due to the potential negative effects with the increased levels of INR and γ-glutamyl transferase and abundance of Bacteroides and Enterococcus [ 92 ]. Therefore, probiotics may augment deleterious immune-mediated processes in patients.…”

A Review of the Phytochemical Properties and Pharmacological Uses of the Genus Pistacia L. (Anacardiaceae)

“…List of compounds identified/isolated from various species of the genus Pistacia. Myrtenol ( 7) Limonene ( 8) Citral (9) α-Phellandrene (10) β-Myrcene (11) Bornyl acetate (12) Terpinen-4-ol ( 13) Myrcene ( 14) p-Mentha-1(7),8-diene (15) Sabinene (16) α-Thujene (17) Camphene (18) p-Cymene (19) cis-Cimene (20) trans-Ocimene (21) β-Phellandrene (22) Limonene dioxide (23) Thymol (24) α-Terpinene (25) α-Terpinolene ( 26) Linalool ( 27)…”

“…Among flavonoids, P. atlantica is found to have 5-hydroxy-8-(4-hydroxyphenyl)-7methoxy-2H-2,2-dimethylpyrano-6H-[2,3-g] chromen-6-one (3-methoxy-carpa-chromene) (125) (8), luteolin (126) (9,18,20,23), luteolin-7-glucoside (127) (9), kaempferol (128) (9), naringenin (129) (9,21), naringenin 7-glucoside (130) (9), (+)-catechin (131) (9), rutin (132) (15,21,22,27,28), catechin (133) (21), quercetin (134) (21,22), eriodictyol (135) (23), and apigenin (136) (23).…”

Lactobacilli Species’ Effects on Liver Function: A Review

“…Another point that makes the comparison between the methodologies of the studies complex is the way of expressing the amount of probiotics administered. Most studies chose to define the amount in CFU (6,8,15,17,18,(21)(22)(23)(24)(25)(26)(27)29,(31)(32)(33)(34). Some works have provided such information in milligrams (1), grams (11), and milliliters (16).…”