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.

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.

Live donor liver transplantation for antitubercular drug-induced acute liver failure.

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.

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.

Acute liver failure due to zinc phosphide containing rodenticide poisoning: Clinical features and prognostic indicators of need for liver transplantation.

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.

Challenges and Outcome of Left-lobe Liver Transplants in Adult Living Donor Liver Transplants.

Adult-to-adult living donor liver transplant (LDLT) frequently depend on using the right-lobes of the donor for obtaining adequate graft-to-recipient weight ratio (GRWR) of over 0.8% in the recipient. However, left-lobes remain an important option in adults, since the morbidity in the donor is considerably less with left donor hepatectomy when compared with right side liver resection. Further benefits of left-lobes in LDLT include more predictable anatomy of the left hepatic duct and left portal vein, which are usually long and single resulting in easier anastomosis in the recipient. Likewise, left-lobe grafts are easier to implant with an excellent venous outflow through the combined orifice of left and middle hepatic vein, as opposed to the complex hepatic vein reconstruction required in right-lobe grafts. However, left hepatic artery is often multiple unlike the right hepatic artery. The holy grail of left-lobe transplants is avoidance of small for size syndrome (SFSS) in the recipients. The strategies for overcoming SFSS currently depend on circumventing portal hyperperfusion in the graft. Measurement of portal pressure and modulating it if high, by splenic artery ligation, splenectomy, or hemiportocaval shunts are proving successful in avoiding SFSS. The future aim in adult LDLT should be to use the left-lobe as much as possible for the benefit of the donor at the same time avoiding SFSS even at very low GRWR for the benefit of the recipient.