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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., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

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., (© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

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., (© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: In adult right lobe living donor liver transplantation (LDLT), venous drainage of the anterior sector is usually reconstructed on the bench to form a neo-middle hepatic vein (MHV). Reconstruction of the MHV for drainage of the anterior sector is crucial for optimal graft function. The conduits used for reconstruction include cryopreserved allografts, synthetic grafts, or the recipient portal vein. However, the ideal choice remains a matter of debate. This study compares the efficacy of the native recipient portal vein (RPV) with PTFE grafts for reconstruction of the neo-MHV., Methods: Patients in this equivalence-controlled, parallel-group trial were randomized to either RPV (62 patients) or PTFE (60 patients) for use in the reconstruction of the neo-MHV. Primary endpoint was neo-MHV patency at 14 days and 90 days. Secondary outcomes included 90-day mortality and post-transplant parameters as scored by predefined scoring systems., Results: There was no statistically significant difference in the incidence of neo-MHV thrombosis at 14 days (RPV 6.5 per cent versus PTFE 10 per cent; P = 0.701) and 90 days (RPV 14.5 per cent versus PTFE 18.3 per cent; P = 0.745) between the two groups. Irrespective of the type of graft used for reconstruction, 90-day all-cause and sepsis-specific mortality was significantly higher among patients who developed neo-MHV thrombosis. Neo-MHV thrombosis and sepsis were identified as risk factors for mortality on Cox proportional hazards analysis. No harms or unintended side effects were observed in either group., Conclusion: In adult LDLT using modified right lobe graft, use of either PTFE or RPV for neo-MHV reconstruction resulted in similar early patency rates. Irrespective of the type of conduit used for reconstruction, neo-MHV thrombosis is a significant risk factor for mortality., Registration Number: CTRI/2018/11/016315 (www.ctri.nic.in)., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Corticosteroids are an integral part of immunosuppression following solid organ transplantation, despite their metabolic complications. We conducted a randomized trial to evaluate the efficacy of steroid-free immunosuppression following live donor liver transplantation (LDLT)., Methods: We randomized 104 patients stratified based on pre-transplant diabetic status to either a steroid-free arm (SF-arm) (Basiliximab + Tacrolimus and Azathioprine,n = 52) or Steroid arm (S-Arm) (Steroid + Tacrolimus + Azathioprine,n = 52). The primary endpoint was the occurrence of metabolic complications (new-onset diabetes after transplant (NODAT), new-onset systemic hypertension after transplant (NOSHT), post-transplant dyslipidemia) within 6 months after transplant. Secondary endpoints included biopsy-proven acute rejection (BPAR) within six months, patient and graft survival at 6 months., Results: The incidence NODAT was significantly higher in S-arm at 3 months (64.5%vs. 28.1%,p-0.004) and 6 months (51.6% vs. 15.6%,p-0.006). Likewise, the incidence of NOSHT (27.8% vs. 4.8%,p-0.01) and hypertriglyceridemia (26.7% vs. 8%,p-0.03) at six months was significantly higher in S-arm. However, there were no differences in BPAR (19.2% vs. 21.2%, p-0.81), time to first rejection (58 vs. 53 days, p-0.78), patient and graft survival (610 vs. 554 days,p- 0.22)., Conclusion: Following LDLT, basiliximab induction with tacrolimus and azathioprine maintenance resulted in significantly lower metabolic complications compared to the triple-drug regimen of steroid, tacrolimus, and azathioprine., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

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.

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., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

Arboviral transmission through transplanted organs is rare. We report a highly probable case of dengue viral transmission during live donor liver transplantation. Fever with severe thrombocytopenia was observed in the donor and recipient within 6 and 9 days after transplantation, respectively. Dengue diagnosis was confirmed by testing blood and explant tissue from the donor and recipient using dengue-specific NAT (nucleic acid testing) and serology. Serology indicated the donor had secondary dengue infection that ran a mild course. However, the dengue illness in the recipient was severe and deteriorated rapidly, eventually proving fatal. The recipient's explant liver tissue tested negative for viral RNA indicative of a pretransplant naïve status. The prM-Envelope gene sequence analysis of the donor and recipient viral RNA identified a similar serotype (DENV1) with almost 100% sequence identity in the envelope region. Molecular phylogenetic analysis of donor and recipient viral envelope sequences with regional and local dengue strains further confirmed their molecular similarity, suggesting a probable donor-to-recipient transmission via organ transplantation. Screening of living donors for dengue virus may be considered in endemic regions., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Introduction: In live donor liver transplantation (LDLT), bile duct division is a critical step in donor hepatectomy. Biliary complications hence are a feared sequelae even among donors. Long term data on biliary complications in donors from India are sparse., Methods: Prospective evaluation of 452 live donors over 10 years was performed to ascertain the incidence & risk factors of clinically significant biliary complications., Results: Of the 452 donor hepatectomies (M: F = 114:338, median age = 38), 66.2% (299) were extended right lobe grafts, 24.1% (109) modified right lobe and 9.7% (44) were left lobe grafts. Portal vein anatomy was Type-I in 85% (386), Type-II in 7.5% (34) and Type-III in 7.1% (32). Following donor hepatectomy, a single bile duct opening occurred only in 46.5% (210) of the grafts. Of the remaining 53.5% grafts, 2 ductal openings were noted in 217 (48%) and three ductal openings in 25 (5.5%). Incidence of multiple openings in the duct were more commonly noted in Type II (70.6%) and III (75%) portal vein anatomy than in grafts with Type I (50.4%) portal anatomy (P = 0.001) Bile leak was noted in 15 (3.3%) donors which included one broncho-biliary fistula and bilio-pleural fistula. Analysis revealed no association between post-operative biliary complications and type of graft, portal vein anatomy or biliary anatomy. There was a single mortality in this series secondary to biliary sepsis. On long term follow, there were no biliary strictures in any of the patients., Conclusions: Biliary complications although rare (3.3%), present significant peri-operative morbidity to the donors., (Copyright © 2017 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

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., (© 2018 by the American Association for the Study of Liver Diseases.)

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., (Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

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.

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.

Antitubercular therapy (ATT)-induced hepatotoxicity is often over looked and active tuberculosis is considered a contraindication for liver transplantation, however it might be the only lifesaving option to certain patients of acute liver failure (ALF) due to ATT. We have assessed the outcome of live donor liver transplantation in ATT-induced ALF. A retrospective analysis of all the cases of ALF that underwent liver transplantation from 2006 to 2014 at the Amrita Institute of Medical Sciences was done. A total of seven (7.7%) patients with ATT-induced ALF who had underwent live donor liver transplantation were included in the study. Out of seven patients, three (42.8%) had established diagnosis of tuberculosis and the remaining (58.2%) patients were started on ATT empirically. The median duration of ATT intake was 2 months. All the patients underwent live donor liver transplant as they met King's College criteria, and their model for end-stage liver disease score was above 35 on admission, receiving graft from first degree relatives. Histopathology of explant liver showed pan acinar necrosis. Restarting of ATT after transplant was individualized. It was restarted only in two (28%) patients with prior sputum-positive pulmonary tuberculosis after a median time of 27 days after transplant. ATT was not restarted in rest of the (72%) patients. Postoperative mortality was seen in two (28%) patients due to conditions that masquerade the ATT-induced acute liver failure. The overall survival rate was 71.4% with a median follow up of 22 months. Live donor-related transplantation is feasible option in ATT-induced acute liver failure. Restarting of ATT post liver transplant is feasible and should be individualized along with frequent monitoring of immunosuppressant levels; however, if the primary diagnosis of tuberculosis was empirical, reintroduction of ATT can be omitted.

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., (© 2016 American Association for the Study of Liver Diseases.)

A 44-year-old man with hepatitis B virus (HBV)-related cirrhosis underwent living donor liver transplantation at our institute. Induction of immunosuppression was achieved with basiliximab, due to deranged renal function, and maintained with prednisolone, tacrolimus and mycophenolate mofetil. The intraoperative and immediate postoperative periods were fairly uneventful. A duplex scan, taken during the third week post-transplantation due to sudden rise in liver enzymes, revealed multifocal hypoechoic lesions in the graft liver with normal Doppler parameters. Multidetecor computed tomography (MDCT) showed multiple hypodense vessel-sparing lesions in the graft liver. Cultures from the aspirate grew filamentous fungi identified as Basidiobolus ranarum species. Despite multiple broad spectrum antifungal infusions including liposomal amphotericin, itraconazole, caspofungin and posaconazole, serial sonography showed the hepatic lesions increasing in size, and involving segments V, VI and VII. The patient developed severe liver dysfunction ultimately progressing to sepsis, multiorgan dysfunction and death., (2016 BMJ Publishing Group Ltd.)

Zinc phosphide (ZnP) containing rodenticide poisoning is a recognized cause of acute liver failure (ALF) in India. When standard conservative measures fail, the sole option is liver transplantation. Records of 41 patients admitted to a single centre with ZnP-induced ALF were reviewed to identify prognostic indicators for requirement of liver transplantation. Patients were analyzed in two groups: group I (n = 22) consisted of patients who either underwent a liver transplant (n = 14) or died without a transplant (n = 8); group II (n = 19) comprised those who survived without liver transplantation. International normalized ratio (INR) in group I was 9 compared to 3 in group II (p < 0.001). Encephalopathy occurred only in group I. Model for End-Stage Liver Disease (MELD) score in group I was 41 compared to 24 in group II (p < 0.001). MELD score of 36 (sensitivity of 86.7 %, specificity of 90 %) or a combination of INR of 6 and encephalopathy (sensitivity of 100 %, specificity of 83 %) were the best indicators of mortality. Such patients should undergo urgent liver transplantation.