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.

Prostaglandins for adult liver transplanted recipients.

BACKGROUND: Prostaglandins are naturally occurring lipids that are synthesised from arachidonic acid. Multiple studies have evaluated the benefits of prostaglandins in reducing ischaemia reperfusion injury after liver transplantation. New studies have been published since the previous review, and hence it was important to update the evidence for this intervention. OBJECTIVES: To evaluate the benefits and harms of prostaglandins in adults undergoing liver transplantation compared with placebo or standard care. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 27 December 2022. SELECTION CRITERIA: We included randomised clinical trials evaluating prostaglandins initiated in the perioperative period compared with placebo or standard care for adults undergoing liver transplantation. We included trials irrespective of reported outcomes. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. all-cause mortality, 2. serious adverse events, and 3. health-related quality of life. Our secondary outcomes were 4. liver retransplantation, 5. early allograft dysfunction, 6. primary non-function of the allograft, 7. acute kidney failure, 8. length of hospital stay, and 9. adverse events considered non-serious. We used GRADE to assess certainty of evidence. MAIN RESULTS: We included 11 randomised clinical trials with 771 adult liver transplant recipients (mean age 47.31 years, male 61.48%), of whom 378 people were randomised to receive prostaglandins and 393 people were randomised to either placebo (272 participants) or standard care (121 participants). All trials were published between 1993 and 2016. Ten trials were conducted in high- and upper-middle-income countries. Prostaglandins may reduce all-cause mortality up to one month (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.61 to 1.23; risk difference (RD) 21 fewer per 1000, 95% CI 63 fewer to 36 more; 11 trials, 771 participants; low-certainty evidence). Prostaglandins may result in little to no difference in serious adverse events (RR 0.92, 95% CI 0.60 to 1.40; RD 81 fewer per 1000, 95% CI 148 fewer to 18 more; 6 trials, 568 participants; low-certainty evidence). None of the included trials reported health-related quality of life. Prostaglandins may result in little to no difference in liver retransplantation (RR 0.98, 95% CI 0.49 to 1.96; RD 1 fewer per 1000, 95% CI 33 fewer to 62 more; 6 trials, 468 participants; low-certainty evidence); early allograft dysfunction (RR 0.62, 95% CI 0.33 to 1.18; RD 137 fewer per 1000, 95% CI 241 fewer to 47 more; 1 trial, 99 participants; low-certainty evidence); primary non-function of the allograft (RR 0.58, 95% CI 0.26 to 1.32; RD 23 fewer per 1000, 95% CI 40 fewer to 16 more; 7 trials, 624 participants; low-certainty evidence); and length of hospital stay (mean difference (MD) -1.15 days, 95% CI -5.44 to 3.14; 4 trials, 369 participants; low-certainty evidence). Prostaglandins may result in a large reduction in the development of acute kidney failure requiring dialysis (RR 0.42, 95% CI 0.24 to 0.73; RD 100 fewer per 1000, 95% CI 132 fewer to 49 fewer; 5 trials, 477 participants; low-certainty evidence). The evidence is very uncertain about the effect of prostaglandins on adverse events considered non-serious (RR 1.19, 95% CI 0.42 to 3.36; RD 225 fewer per 1000, 95% CI 294 fewer to 65 fewer; 4 trials, 329 participants; very low-certainty evidence). Two trials reported receiving funding; one of these was with vested interests. We found one registered ongoing trial. AUTHORS' CONCLUSIONS: Eleven trials evaluated prostaglandins in adult liver transplanted recipients. Based on low-certainty evidence, prostaglandins may reduce all-cause mortality up to one month; may cause little to no difference in serious adverse events, liver retransplantation, early allograft dysfunction, primary non-function of the allograft, and length of hospital stay; and may have a large reduction in the development of acute kidney injury requiring dialysis. We do not know the effect of prostaglandins on adverse events considered non-serious. We lack adequately powered, high-quality trials evaluating the effects of prostaglandins for people undergoing liver transplantation.

Open to robotic right donor hepatectomy: A tectonic shift in surgical technique.

Robotic right live donor hepatectomy (r-LDRH) has been reported with reduced morbidity compared to open donor right hepatectomy (o-LDRH) in few recent series. Nevertheless, its routine use is debated. We present a large series comparing pure r-LDRH with o-LDRH. Consecutive r-LDRH performed from June 2018 to June 2020 (n = 102) were compared with consecutive donors undergoing o-LDRH (n = 152) from February 2016 to February 2018, a period when r-LDRH was not available at this center. Propensity score matched (PSM) analysis of 89 case-control pairs was additionally performed. Primary endpoints were length of high dependency unit (HDU) and hospital stay and Clavien-Dindo graded complications among donors. Although r-LDRH took longer to perform (540 vs. 462 min, P < .001), the postoperative peak transaminases levels (P < .001), the length of HDU (3 vs. 4 days, P < .001), and hospital stay (8 vs. 9 days, P < .001) were lower in in donors undergoing r-LDRH. Clavien-Dindo graded complications were similar (16.67% in r-LDRH and 13.16% in o-LDRH). The rates of early allograft dysfunction (1.6% vs. 3.3%), bile leak (14.7% vs. 10.7%), and 1-year mortality (13.7% vs. 11.8%) were comparable between r-LDRH and o-LDRH recipients. PSM analysis yielded similar results between the groups. These data support the safety and feasibility of r-LDRH in select donors.

Technique of robotic right donor hepatectomy.

BACKGROUND: Although minimally invasive right donor hepatectomy (RDH) has been reported, this innovation is yet to be widely accepted by transplant community. Bleeding during transection, division of right hepatic duct (RHD), suturing of donor duct as well as retrieval with minimal warm ischemia are the primary concerns of most donor surgeons. We describe our simplified technique of robotic RDH evolved over 144 cases. PATIENTS AND METHODS: Right lobe mobilization is performed in a clockwise manner from right triangular ligament over inferior vena cavae up to hepatocaval ligament. Transection is initiated using a combination of bipolar diathermy and monopolar shears controlled by console surgeon working in tandem with lap CUSA operated by assistant surgeon. With the guidance of indocyanine green cholangiography, RHD is divided with robotic endowrist scissors (Potts), and remnant duct is sutured with 6-0 PDS. Final posterior liver transection is completed caudocranial without hanging manoeuvre. Right lobe with intact vascular pedicle is placed in a bag, vascular structures then divided, and retrieved through Pfannenstiel incision. CONCLUSION: Our technique may be easy to adapt with the available robotic instruments. Further innovation of robotic platform with liver friendly devices could make robotic RDH the standard of care in future.

Middle hepatic vein reconstruction in adult living donor liver transplantation: a randomized clinical trial.

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).

Randomized trial of steroid free immunosuppression with basiliximab induction in adult live donor liver transplantation (LDLT).

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.

Dengue virus transmission from live donor liver graft.

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.

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.

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.

Biliary complications among live donors following live donor liver transplantation.

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.

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.

A Short Review on Obeticholic Acid: An Effective Modulator of Farnesoid X Receptor.

Farnesoid X receptor (FXR) was identified as an orphan nuclear receptor resembling the steroid receptor in the late '90s. Activation of FXR is a crucial step in many physiological functions of the liver. A vital role of FXR is impacting the amount of bile acids in the hepatocytes, which it performs by reducing bile acid synthesis, stimulating the bile salt export pump, and inhibiting its enterohepatic circulation, thus protecting the hepatocytes against the toxic accumulation of bile acids. Furthermore, FXR mediates bile acid biotransformation in the intestine, liver regeneration, glucose hemostasis, and lipid metabolism. In this review, we first discuss the mechanisms of the disparate pleiotropic actions of FXR agonists. We then delve into the pharmacokinetics of Obeticholic acid (OCA), the first-in-class selective, potent FXR agonist. We additionally discuss the clinical journey of OCA in humans, its current evidence in various human diseases, and its plausible roles in the future.

Co-relation of Portal Vein Tumour Thrombus Response With Survival Function Following Robotic Radiosurgery in Vascular Invasive Hepatocellular Carcinoma.

Background/aims: The aim of this study was to prospectively evaluate stereotactic body radiotherapy (SBRT) with robotic radiosurgery in hepatocellular carcinoma patients with macrovascular invasion (HCC-PVT). Materials and methods: Patients with inoperable HCC-PVT, good performance score (PS0-1) and preserved liver function [up to Child-Pugh (CP) B7] were accrued after ethical and scientific committee approval [Clinical trial registry-India (CTRI): 2022/01/050234] for treatment on robotic radiosurgery (M6) and planned with Multiplan (iDMS V2.0). Triple-phase contrast computed tomography (CT) scan was performed for contouring, and gross tumour volume (GTV) included contrast-enhancing mass within main portal vein and adjacent parenchymal disease. Dose prescription was as per risk stratification protocol (22-50 Gy in 5 fractions) while achieving the constraints of mean liver dose <15 Gy, 800 cc liver <8 Gy and the duodenum max of <24 Gy). Response assessment was done at 2 months' follow-up for recanalization. Patient- and treatment-related factors were evaluated for influence in survival function. Results: Between Jan 2017 and May 2022, 318 consecutive HCC with PVT patients were screened and 219 patients were accrued [male 92%, CP score: 5-7 90%, mean age: 63 years (38-85 yrs), Cancer of the Liver Italian Program <3: 84 (40%), 3-6117 (56%), infective aetiology 9.5%, performance status (PS): 0-37%; 1-56%]. Among 209 consecutive patients accrued for SBRT treatment (10 patients were excluded after accrual due to ascites and decompensation), 139 were evaluable for response assessment (>2 mo follow-up). At mean follow-up of 12.21 months (standard deviation: 10.66), 88 (63%) patients expired and 51 (36%) were alive. Eighty-two (59%) patients had recanalization of PVT (response), 57 (41%) patients did not recanalize and 28 (17%) had progressive/metastatic disease prior to response evaluation (<2 months). Mean overall survival (OS) in responders and non-responders were 18.4 [standard error (SE): 2.52] and 9.34 month (SE 0.81), respectively (P < 0.001). Mean survival in patients with PS0, PS1 and PS2 were 17, 11.7 and 9.7 months (P = 0.019), respectively. OS in partial recanalization, bland thrombus and complete recanalization was 12.4, 14.1 and 30.3 months, respectively (P-0.002). Adjuvant sorafenib, Barcelona Clinic Liver Classification stage, gender, age and RT dose did not influence response to treatment. Recanalization rate was higher in good PS patients (P-0.019). OS in patients with response to treatment, in those with no response to treatment, in those who are fit but not accrued and in those who are not suitable were 18.4, 9.34, 5.9 and 2.6 months, respectively (P-<0.001). Thirty-six of 139 patients (24%) had radiation-induced liver disease (RILD) [10 (7.2%) had classic RILD & 26 (19%) had non-classic RILD]. Derangement in CP score (CP score change) by more than 2 was seen in 30 (24%) within 2-month period after robotic radiosurgery. Eighteen (13%) had unplanned admissions, two patients required embolization due to fiducial-related bleeding and 20 (14%) had ascites, of which 9 (6%) patients required abdominocentesis. Conclusion: PVT response or recanalization after SBRT is a statistically significant prognostic factor for survival function in HCC-PVT.

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.

Liver Transplant in Acute Liver Failure - Looking Back Over 10 Years.

BACKGROUND: Acute liver failure (ALF) is the leading cause for emergency liver transplantation (LT) all over the world. We looked at the profile of cases who required LT for ALF from a single centre to identify the possible predictors of poor outcomes. METHODOLOGY: During the 10-year period starting from 2007, 320 cases of ALF were treated at our institution, of which 70 (median age 24 years, Male:Female 1:2) underwent LT. Retrospective analyses of these 70 patients were performed. RESULTS: Etiology was identifiable in 73% (n = 51) of cases (yellow phosphorous [YP] poisoning [n = 16], Hepatitis A virus [HAV] [n = 15], Hepatitis B virus [HBV] [n = 5], Hepatitis E virus [HEV] [n = 1], anti-tubercular therapy [ATT] induced [n = 6], acute Wilson's [n = 3], and autoimmune [n = 5]]. Upon meeting King's College Hospital criteria, 69 had live donor LT (61 right lobe grafts, three left lobe grafts, five left lateral segment grafts) and one had deceased donor LT. Among these, there were five auxiliary partial orthotopic grafts and four ABO-incompatible transplants. Overall, 90-day mortality was 35.7% (n = 25), predominantly due to sepsis. Significant risk factors for mortality on multivariate analysis included indeterminate etiology, pre-op renal dysfunction, and Grade IV hepatic encephalopathy (HE). Cumulative 10-year survival of the remaining survivors was 95.6% (n = 45). CONCLUSION: LT for ALF carries high perioperative mortality (35.7%) in those presenting with indeterminate etiology, pre-op renal dysfunction, and Grade IV HE. Nevertheless, if they survive the perioperative period, long-term survival is excellent.

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.

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.