Double-blind placebo-controlled randomized trial of N-acetylcysteine infusion following live donor liver transplantation.

BACKGROUND: The role of N-acetylcysteine (NAC) in improving outcomes following live donor liver transplantation (LDLT) is not well established. We designed a randomized double-blind placebo-controlled trial to study the role of NAC infusion in recipients undergoing LDLT. METHODS: We assigned 150 patients who underwent LDLT by computer-generated random sequence on 1:1 ratio to either NAC group or placebo group. Patients in the NAC group received NAC infusion which was started at beginning of graft implantation at an initial loading dose of 150 mg/kg/h over 1 h, followed by 12.5 mg/kg/h for 4 h and then at 6.25 mg/kg/h continued for 91 h. Placebo group received normal saline. The primary endpoint was composite occurrence of acute kidney injury (AKI) and early allograft dysfunction (EAD) in the recipient. Secondary endpoints included levels of bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, INR, primary graft non-function, intraoperative bleeding, post-transplant hospital stay and in-hospital mortality. RESULTS: The composite endpoint did not show any significant difference between the NAC and placebo group (21.3% vs 29.3%, p = 0.35). Peak AST (425.65 IU/L vs 702.24 IU/L, p = 0.02) and peak ALT (406.65 IU/L vs 677.99 IU/L, p = 0.01) levels were significantly lower in the study group. Time to normalization of transaminases was also significantly low in the study group. CONCLUSIONS: Perioperative NAC infusion following LDLT resulted in significantly lower postoperative AST and ALT levels. Rapid normalization of transaminases was also observed. This, however, did not translate to improvement in AKI or EAD.

Randomized trial on extended versus modified right lobe grafts in living donor liver transplantation.

Despite advances in the practice of living donor liver transplantation (LDLT), the optimum surgical approach with respect to the middle hepatic vein (MHV) in right lobe LDLT remains undefined. We designed a randomized trial to compare the early postoperative outcomes in recipients and donors between extended right lobe grafts (ERGs; transection plane was maintained to the left of MHV and division of MHV performed beyond the segment VIII vein) and modified right lobe grafts (MRGs; transection plane was maintained to the right of MHV; the segment V and VIII drainage was reconstructed using a conduit of recipient portal vein). Eligible patients (n = 86) were prospectively randomized into the ERG arm (n = 43) and the MRG arm (n = 43) at the beginning of donor hepatectomy. The primary endpoint considered in this equivalence trial was patency of the MHV or the reconstructed "neo-MHV" in the recipient. The secondary endpoints included biochemical parameters, postoperative complications, mortality in recipients as well as donors and volume regeneration of remnant liver in donors, measured at 2 months. The patency of the MHV was comparable in the ERG and MRG arms (90.7% versus 81.4%; difference, 9.3%; 95% confidence interval [CI], -5.8 to 24.4; z score, 1.245; P = 0.21). Volume regeneration of the remnant liver in donors was significantly better in the MRG arm (111.3% versus 87.3%; mean difference, 24%; 95% CI, 14.6-33.3; P < 0.001). The remaining secondary endpoints in donors and recipients were similar between the 2 arms. To conclude, MRG with reconstructed neo-MHV has comparable patency to native MHV in ERG and confers equivalent graft outflow in the recipient. Furthermore, it allows better remnant liver regeneration in the donor at 2 months. Liver Transplantation 24 888-896 2018 AASLD.

Intraductal Transanastomotic Stenting in Duct-to-Duct Biliary Reconstruction after Living-Donor Liver Transplantation: A Randomized Trial.

BACKGROUND: Biliary complications continue to be the "Achilles heel" of living-donor liver transplantation (LDLT). The use of biliary stents in LDLT to reduce biliary complications is a controversial issue. We performed a randomized trial to study the impact of intraductal biliary stents on postoperative biliary complications after LDLT. STUDY DESIGN: Of the 94 LDLTs that were performed during a period of 16 months, ABO-incompatible transplants, left lobe grafts, 3 or more bile ducts on the graft, and those requiring bilioenteric drainage were excluded. Eligible patients were randomized to either a study arm (intraductal stent, n = 31) or a control arm (no stent, n = 33) by block randomization. Stratification was done, based on the number of ducts on the graft requiring anastomosis, into single (n = 20) or 2 ducts (n = 44). Ureteric stents of 3F to 5F placed across the biliary anastomosis and exiting into the duodenum for later endoscopic removal at 3 months were used. The primary end point was postoperative bile leak. RESULTS: Bile leak occurred in 15 of 64 (23.4%), the incidence was higher in the stented group compared with the control group (35.5% vs 12.1%; p = 0.03). Multiplicity of bile ducts and stenting were identified as risk factors for bile leak on multivariate analysis (p = 0.031 and p = 0.032). During a median follow-up of 2 years, biliary stricture developed in 9 patients (14.1%). Postoperative bile leak is a significant risk factor for the development of biliary stricture (p = 0.003). CONCLUSIONS: Intraductal transanastomotic biliary stenting and multiplicity of graft ducts were identified as independent risk factors for the development of postoperative biliary complications.

Quality of life of liver donors following donor hepatectomy.

BACKGROUND: Although morbidity following living liver donation is well characterized, there is sparse data regarding health-related quality of life (HRQOL) of donors. METHODS: HRQOL of 200 consecutive live liver donors from 2011-2014 performed at an Indian center were prospectively collected using the SF-36 version 2, 1 year after surgery. The effect of donor demographics, operative details, post-operative complications (Clavien-Dindo and 50-50 criteria), and recipient mortality on the quality-of-life (QOL) scoring was analyzed. RESULTS: Among 200 donors (female/male=141:59), 77 (38.5%) had complications (14.5%, 16.5%, 4.5%, and 3.5%, Clavien-Dindo grades I-IV, respectively). The physical composite score (PCS) of donors 1 year after surgery was less than ideal (48.75±9.5) while the mental composite score (MCS) was good (53.37±6.16). Recipient death was the only factor that showed a statistically significant correlation with both PCS (p<0.001) and MCS (p=0.05). Age above 50 years (p<0.001), increasing body mass index (BMI) (p=0.026), and hospital stay more than 14 days ( p= 0.042) negatively affected the physical scores while emergency surgery (p<0.001) resulted in lower mental scores. Gender, postoperative complications, type of graft, or fulfillment of 50-50 criteria did not influence HRQOL. On asking the hypothetical question whether the donors would be willing to donate again, 99% reiterated there will be no change in their decision. CONCLUSION: Recipient death, donation in emergency setting, age above 50, higher BMI, and prolonged hospital stay are factors that lead to impaired HRQOL following live liver donation. Despite this, 99% donors did not repent the decision to donate.

Perioperative prostaglandin e1 infusion in living donor liver transplantation: A double-blind, placebo-controlled randomized trial.

The role of prostaglandin E1 (PGE1) infusion in improving early graft function has not been well defined, especially in the scenario of living donor liver transplantation (LDLT). We designed a randomized, double-blind, placebo-controlled trial to evaluate the role of perioperative PGE1 infusion in LDLT. Patients in the study arm received PGE1 (alprostadil) at the rate of 0.25 µg/kg/hour, starting at 1 hour after portal venous reperfusion, and continued for 96 hours. The primary endpoint was early allograft dysfunction (EAD). We analyzed multiple secondary endpoints including postoperative liver function and renal function parameters, acute kidney injury (AKI), hepatic artery thrombosis (HAT), postoperative bleeding, overall mortality, and posttransplant hospital stay. The incidence of EAD was lower in the PGE1 arm, although the difference did not reach statistical significance (22.4% versus 36%; P = 0.21). Among the secondary endpoints, the incidence of AKI was significantly lower in the PGE1 arm (8.2% versus 28%; P = 0.02), as were the peak and mean postoperative creatinine levels. The need for renal replacement therapy was similar between the 2 groups. Among the postoperative graft function parameters, postoperative alanine aminotransferase level was significantly lower in the PGE1 arm (P = 0.04), whereas the remaining parameters including serum bilirubin, aspartate aminotransferase, and international normalized ratio were similar between the 2 arms. There was no difference in the incidence of HAT and postoperative bleeding, in-hospital mortality, and posttransplant hospital stay between the 2 arms. Perioperative PGE1 infusion reduces the incidence of posttransplant renal dysfunction in patients undergoing LDLT. Liver Transplantation 22 1067-1074 2016 AASLD.