Randomized controlled trial of sustained release tacrolimus vs twice daily tacrolimus in adult living donor liver transplantation.

BACKGROUND: To compare the safety and efficacy of once-daily tacrolimus (ODT) versus twice-daily tacrolimus (BDT) in adult live donor liver transplantation (LDLT). METHODS: In this open-labelled randomized trial, 174 adult patients undergoing LDLT were randomized into ODT or BDT, combined with basiliximab induction and mycophenolate mofetil (steroid-free regimen). Tacrolimus was started at a total dose of 1 mg and the trough level was aimed at 3-7 ng/ml. The primary endpoint was eGFR at 1,3- and 6 months post-transplant, using CKD- EPI equation. Secondary endpoints included biopsy-proven acute rejection (BPAR), metabolic complications, post-operative bilio-vascular complications and patient survival. RESULTS: There was no statistically significant difference in eGFR between the two groups at 6 months (ODT -96 ± 19, BDT -91 ± 21, p value-0.164). BPAR was comparable (18/84 in ODT, 19/88 in BDT, p value-0.981). For a similar dosage of tacrolimus, the median trough tacrolimus levels attained were significantly lower for ODT than BDT during the first-month post-transplant (p value-0.001). Metabolic complications due to immunosuppression, post-operative bilio-vascular complications and patient survival was similar between the two groups at 6 months. CONCLUSION: Once-daily tacrolimus has similar renal safety and efficacy as twice-daily tacrolimus when used in combination with basiliximab induction and mycophenolate in adult LDLT.

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

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, placebo-controlled 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 intra-abdominal 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.

Extended criteria donors for robotic right hepatectomy: A propensity score matched analysis.

BACKGROUND: Robotic right donor hepatectomy (RDH) has been reported from experienced centers with reduced morbidity when compared to open RDH. However, outcomes in donors with large grafts/complex biliovascular anatomy are unknown. METHODS: Out of 170 robotic RDH, 100 had one or more of the following: graft weight ≥800 g, type 2/3 portal vein, >1 bile duct or hepatic artery and inferior hepatic veins >5 mm requiring reconstruction (extended criteria donors [ExRDH]), while the remaining 70 had standard anatomy (SRDH). After propensity score matching, 66 ExRDH were compared with 66 SRDH. Additionally, all robotic RDH performed were analyzed in three temporal phases (60, 60, and 50). RESULTS: Peak AST and ALT were higher amongst donors and recipients in the ExRDH arm compared to SRDH. Other intraoperative parameters and postoperative complications were similar between the two groups. During the last phase, donors demonstrated reduction in duration of surgery, postoperative complications, and hospital stay while recipients showed decreased blood loss and hospital stay. CONCLUSION: Robotic right hepatectomy performed in donors with extended criteria have similar perioperative outcomes as standard donors. However, a significant learning curve needs to be traversed. Further studies are required before safely recommending robotic RDH for all donors.

Antegrade Hepatic Artery and Portal Vein Perfusion Versus Portal Vein Perfusion Alone in Living Donor Liver Transplantation: A Randomized Trial.

Traditionally, deceased donor liver grafts receive dual perfusion (DP) through the portal vein and the hepatic artery (HA) either in situ or on the back table. HA perfusion is avoided in living donor liver grafts for fear of damage to the intima and consequent risk of hepatic artery thrombosis (HAT). However, biliary vasculature is predominantly derived from the HA. We hypothesized that antegrade perfusion of the HA in addition to the portal vein on the back table could reduce the incidence of postoperative biliary complications. Consecutive adult patients undergoing living donor liver transplantations were randomized after donor hepatectomy to receive graft perfusion of histidine-tryptophan-ketoglutarate solution either via both the HA and portal vein (DP group, n = 62) or only through the portal vein (standard perfusion [SP] group, n = 62). The primary endpoint was the occurrence of biliary complications (biliary leak/stricture). Secondary endpoints included HAT and patient survival. The incidence of biliary stricture was significantly lower in the DP group (6.5% versus 19.4%; odds ratio, 0.29; 95% confidence interval, 0.09-0.95; P = 0.04). There was no significant reduction in the incidence of HAT, bile leak, or hospital stay between the 2 groups. The 3-year mortality and graft survival rates were significantly higher among patients who received DP compared with SP (P = 0.004 and P = 0.003, respectively). On multivariate analysis, nonperfusion of the HA and preceding bile leak were found to be risk factors for the development of biliary stricture (P = 0.04 and P < 0.001, respectively). In conclusion, DP of living donor liver grafts through both the HA and portal vein on the back table may protect against the development of biliary stricture. This could translate to improved patient survival in the short term.

Living Donor Liver Transplantation Using Small-for-Size Grafts: Does Size Really Matter?

BACKGROUND: In living donor liver transplantation (LDLT), graft-to-recipient weight ratio (GRWR) > 0.8% is perceived as the critical graft size. This lower limit of GRWR (0.8%) has been challenged over the last decade owing to the surgical refinements, especially related to inflow and outflow modulation techniques. Our aim was to compare the recipient outcome in small-for-size (GRWR < 0.8) versus normal-sized grafts (GRWR > 0.8) and to determine the risk factors for mortality when small-for-size grafts (SFSG) were used. METHODS: Data of 200 transplant recipients and their donors were analyzed over a period of two years. Routine practice of harvesting middle hepatic vein (MHV) or reconstructing anterior sectoral veins into neo-MHV was followed during LDLT. Outcomes were compared in terms of mortality, hospital stay, ICU stay, and occurrence of various complications such as functional small-for-size syndrome (F-SFSS), hepatic artery thrombosis (HAT), early allograft dysfunction (EAD), portal vein thrombosis (PVT), and postoperative sepsis. A multivariate analysis was also done to determine the risk factors for mortality in both the groups. RESULTS: Recipient and donor characteristics, intraoperative variables, and demographical data were comparable in both the groups (GRWR < 0.8 and GRWR ≥ 0.8). Postoperative 90-day mortality (15.5% vs. 22.85%), mean ICU stay (10 vs. 10.32 days), and mean hospital stay (21.4 vs. 20.76 days) were statistically similar in the groups. There was no difference in postoperative outcomes such as occurrence of SFSS, HAT, PVT, EAD, or sepsis between the groups. Thrombosis of MHV/reconstructed MHV was a risk factor for mortality in grafts with GRWR < 0.8 but not in those with GRWR > 0.8. CONCLUSION: Graft survival after LDLT using a small-for-size right lobe graft (GRWR < 0.8%) is as good as with normal grafts. However, patency of anterior sectoral outflow by MHV or reconstructed MHV is crucial to maintain graft function when SFSG are used.

A New Score to Predict Recipient Mortality from Preoperative Donor and Recipient Characteristics in Living Donor Liver Transplantation (DORMAT Score).

BACKGROUND Recipient outcomes in adult living donor liver transplantation depend on various characteristics in both recipient and donor. We aimed to derive a score based upon preoperative characteristics in donor and recipient that could predict the recipient mortality in adult living donor liver transplantation. MATERIAL AND METHODS Retrospective data of 100 living donor liver transplantation recipients and their respective donors were analyzed for preoperative factors that correlated with recipient mortality. Statistically significant factors were weighted appropriately to derive a regression equation to obtain a donor-to-recipient match (DORMAT) score. This score was applied to 71 patients prospectively and their outcome was analyzed. RESULTS Donor-recipient match (DORMAT) score, derived using regression analysis of the significant variables was [0.002 (Recipient age) + 0.013 (Recipient BMI) + 0.055 (SBP) + 0.344 (HRS) + 0.022 (Pre-op culture positivity) + 0.01 (Donor age) - 0.639]×100. DORMAT score, when validated to a prospective cohort of 71 adult-to-adult LDLT patients, had a C-statistic (area under ROC curve) of 0.712. The mortality rate was seen to increase with increasing DORMAT score. CONCLUSIONS DORMAT score is a useful clinical decision-making tool to predict recipient mortality in adult living donor liver transplantation.