Safety and feasibility of immediate tracheal extubation of small pediatric patients after living donor liver transplantation.

BACKGROUND: Immediate extubation is integral constituent of enhance recovery protocols. Purpose of this study was to examine success rates and safety of protocolized immediate extubation in pediatric living donor liver transplant recipients and to find out factors associated with non-immediate extubation in operation room. METHODS: We performed retrospective analysis for data of small (≤20 kg) pediatric patients transplanted between 2017 and 2019 (protocolized duration) and compared with data of transplants done between 2014 and 2016 (non-protocolized duration). Further, we compared data during each time duration between immediate extubation and non-immediate extubation group to find risk factors in that particular duration. RESULTS: Immediate extubation rates were significantly higher during protocolized duration compared with non-protocolized duration (85.52% vs. 48.29%, p < .001). Reintubation rates decreased during protocolized duration (10.9% vs. 4.6%). Hospital stays (20.47 ± 7.06 vs. 27.8 ± 6.2 days, p < .001) and mortality (13.2% vs. 28%, p = .04) were significantly decreased in protocolized duration. Higher age (OR: 2.85, 95% CI 1.22-6.67, p = .02), weight > 10 (OR: 4.37, 95% CI 1.16-16.46, p = .029) and high vasopressor support (OR: 32, 95% CI 6.4-160.13, p < .001) found as significant predictors of non-immediate extubation however only high vasopressor support found to be independent predictor during protocolized duration. CONCLUSIONS: Outcomes in pediatric transplants can be optimized by immediate extubation in majority of cases when protocolized as part of policy.

Protocol to ensure continued pediatric liver transplantation service during the COVID pandemic and the encouraging outcomes.

Coronavirus disease 2019 is a global pandemic, and to deal with the unexpected, enormous burden on healthcare system, liver transplantation (LT) services have been suspended in many centers. Development of robust and successful protocols in preventing the disease among the recipients, donors and healthcare workers would help in re-starting the LT programs. We adapted a protocol at our center, which is predominantly a living donor liver transplant center based in north India, and continued the service as the pandemic unfolded and peaked in India with good results and shared the experience of the same. Between March 24 and June 7, 2020, during the government-enforced public curfew-"lockdown"-7 children received LT. The protocols of infection control were drafted in our team by local customization of published guidelines. The number of pediatric LT done during the lockdown period in 2020 was similar to that done in corresponding pre-COVID period in 2019. The outcomes were of 100% survival, and none of recipients developed COVID. One potential donor was asymptomatic positive for COVID, responded well to conservative treatment, and was later accepted as a donor. LT program during the COVID pandemic can successfully function after putting in place standard protocols for infection control. These can be implemented with minimal extra involvement of healthcare infrastructure, hence without diversion of resources from COVID management. In conclusion, pediatric liver transplantation services can be continued amid COVID-19 pandemic after establishing a properly observed protocol with minimum additional resources.

Managing Recipient Hepatic Artery Intimal Dissection During Living Donor Liver Transplantation.

Recipient hepatic artery intimal dissection (HAD) followed by hepatic artery thrombosis (HAT) is a serious complication of liver transplantation. Once this is recognized intraoperatively, the accepted approach is to use an alternative arterial inflow, which may not be possible in all patients. We describe a new classification and technique for the management of HAD during living donor liver transplantation. On the basis of the longitudinal extent of intimal dissection, HAD was classified into 4 types. Management was based on the type of dissection, availability of an adequate length of hepatic artery (HA), and an alternate source of inflow. The dissected HA itself was used for arterial anastomosis in patients with preserved pulsatile flow in the dissected artery and a lack of an alternative source of arterial inflow. The technique of using the dissected artery was based on close approximation of the tunica intima to the media with the first 2 sutures of the arterial anastomosis. Of 47 (2.4%) patients who developed HAD, 22 (46.8%) had a type 2 dissection for whom the other (right or the left) undissected HA was used for the anastomosis, and 20 (42.6%) had major (type 3 or 4) dissection. The dissected artery was used for the anastomosis in 9 (45%) of these patients. Postoperative HAT developed in only 1 of 9 patients. Pre-existing portal vein thrombosis and prior transarterial embolization were found to be major risk factors for the development of HAD. Using the technique described, the dissected artery can be successfully used for a satisfactory HA anastomosis with low thrombosis rates.

Minimum absolute graft weight of 650 g predicts a good outcome in living donor liver transplant despite a graft recipient body weight ratio of less than 0.8.

In living donor liver transplant (LDLT), it is recommended to have a minimum graft recipient body weight ratio (GRBWR) 0.8 for good outcomes. Recent reports have, however, shown that good outcomes can be obtained even with GRBWR less than 0.8. We hypothesized that in patients receiving a graft with GRWR less than 0.8 absolute graft weight rather than GRBWR may be more relevant for predicting good outcome. Early post-transplant outcomes were assessed in adult patients undergoing elective right lobe LDLT. Patients were categorized as having good (survival) or poor (mortality) outcome. A ROC curve was drawn based on their graft weights and a cutoff value that provided the highest sensitivity and specificity for a good outcome was chosen. 147 patients received right lobe grafts with GRBWR less than 0.8. The 90-day mortality rate was 13.6% (n = 20). AUROC was 67.7%. Graft weight cutoff of 643 g gave the best combination of sensitivity (51.2%) and specificity (77.8%). There were 15 (19.4%) deaths in group with graft weight less than 643 g compared to 5 (7.1%) patients with graft weight 643 g or above. This cutoff value of 643 g (rounded of to 650 g) gave a positive predictive value (PPV) of 94%.

Living Donor Liver Transplantation Alone Is Not Inferior to Combined Kidney Liver Transplant for Cirrhotic Patients With Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is common in patients with chronic liver disease (CLD) as is acute kidney injury (AKI). The differentiation between CKD vs AKI is often difficult and sometimes the both may coexist. A combined kidney-liver transplant (CKLT) may result in a kidney transplant in patients whose renal function is likely to recover or at least who have stable renal function post-transplant. We retrospectively enrolled 2742 patients who underwent living donor liver transplant at our center from 2007 to 2019. METHODS: This audit was carried out in liver transplant recipients with CKD 3 to 5 who underwent either liver transplant alone (LTA) or CKLT to look at outcomes and long-term evolution of renal function. Forty-seven patients met the medical eligibility criteria for CKLT. Of the 47 patients, 25 underwent LTA and the rest 22 underwent CKLT. The diagnosis of CKD was made according to the Kidney Disease: Improving Global Outcomes classification. RESULTS: Preoperative renal function parameters were comparable between the 2 groups. However, CKLT patients had significantly lower glomerular filtration rates (P = .007) and higher proteinuria (P = .01). Postoperatively, renal function, and comorbidities were comparable between the 2 groups. Survival was similar at 1, 3, and 12 months, respectively (log-rank; P = .84, = .81, and = .96, respectively). At the end of the study period, 57% of patients who survived in LTA groups had stabilized renal function (Creatinine = 1.8 ± 0.6 mg/dL). CONCLUSIONS: Liver transplant alone is not inferior to CKLT in living donor situations. Renal dysfunction is stabilized in the long term whereas long-term dialysis may be carried out in others. Living donor liver transplantation alone is not inferior to CKLT for cirrhotic patients with CKD.

Serum Tumor Necrosis Factor-Alpha Levels in Acute Leukemia and Its Prognostic Significance.

Introduction Tumor necrosis factor-alpha (TNF-α) is a pleiotropic cytokine that facilitates malignant cells in immune evasion, survival, and treatment resistance by generating a favorable milieu for them. It is shown to be ectopically produced by malignant/leukemic and immune cells in the tumor microenvironment, providing a tumor-supportive environment and playing an important part in the establishment and progression of malignant cells. It is linked to hyperleukocytosis, high blast count, and poor clinical outcomes in acute leukemia (AL). Considering the varied role and different expression patterns of tumor necrosis factor-alpha in acute leukemia and its clinical relevance, the present study was planned to monitor the level of tumor necrosis factor-alpha in patients with acute leukemia and its correlation with disease outcome. The aim of this study was to monitor the level of tumor necrosis factor-alpha in patients with acute leukemia at the time of diagnosis and after induction chemotherapy. Material and methods The study included cases classified as acute leukemia based on morphological examination, bone marrow analysis, and flow cytometry. In all patients with acute leukemia (n = 90) and controls (n = 10), the serum tumor necrosis factor-alpha level was measured using a Diaclone Human ELISA kit (Diaclone, Besancon, France) (solid phase sandwich ELISA) at diagnosis and after induction chemotherapy. Results Tumor necrosis factor-alpha levels were substantially higher in T-acute lymphoblastic leukemia (T-ALL) cases, followed by acute myeloid leukemia (AML) and B-acute lymphoblastic leukemia (B-ALL), at the time of diagnosis, compared to the control. A significant reduction in serum tumor necrosis factor-alpha level was seen in patients with acute leukemia after induction phase chemotherapy (P < 0.05). Tumor necrosis factor-alpha levels were considerably reduced (P < 0.001) in the majority of acute leukemia cases after the induction phase, while high tumor necrosis factor-alpha levels were positively correlated with incomplete remission status in the remaining cases. Conclusion Tumor necrosis factor-alpha is involved in the progression of acute leukemia and its relapse. High levels of tumor necrosis factor-alpha are linked to leukocytosis, high blast counts, and worse survival in patients with acute leukemia. Monitoring of tumor necrosis factor-alpha may be helpful in patients with acute leukemia in view of available antitumor necrosis factor-alpha therapy.

Outcome of Pediatric Liver Transplants in Patients With Less Than 10 kg of Body Weight Is Not Worse.

OBJECTIVES: Liver transplant in pediatric patients with body weight < 10 kg poses a challenge to the entire liver transplant team. Many reports have considered 10 kg to be a cutoff pointfor body weightforfavorable posttransplant outcomes. With evolving surgical techniques and postoperative management, there is potential to improve outcomes in this subset of recipients. We compared the outcomes in pediatric patients with body weight < 10 kg with those > 10 kg; also, we studied the factors of influence. MATERIALS AND METHODS: We performed a retrospective analysis to evaluate the outcomes of liver transplants in pediatric patients with < 10 kg body weight. The cohort consisted of 90 children subdivided into the following 2 subgroups: group A (n = 35) with > 10 kg body weight at liver transplant and group B (n = 55) with < 10 kg body weight at liver transplant. We compared the following pretransplant characteristics between the groups: graft weight, graft-to-recipient weightratio, cold ischemia time, warm ischemia times, and liver transplant outcomes. RESULTS: Pediatric End-stage Liver Disease score was significantly higher in group B (score of 24) versus group A (score of 18). Group B had significantly higher graft-to-recipient weight ratio (2.8 in group B vs 1.7 in group A). Graft function showed no significant difference between the 2 groups. Portal vein thrombosis was seen only in group B, whereas biliary leaks were observed among 5 patients in group B and 1 patientin group A. Patient survivalrate was higherin group B (86%) than in group A (77%). CONCLUSIONS: Pediatric patients weighing < 10 kg have similarif not better survivalrates after liver transplant compared with patients > 10 kg. Advancements in surgical techniques and a careful monitoring for complications and timely intervention are important to facilitate these outcomes.

Significant association between FOXP3 gene polymorphism and steroid-resistant acute rejection in living donor liver transplantation.

Previous studies have found that preferential accumulation of regulatory T (Treg) cells in liver allografts during acute cellular rejection (ACR) is associated with less severe rejection, suggesting a role of Treg cells in preventing excessive progress of ACR. We investigated the impact of single nucleotide polymorphisms (SNPs) in the Forkhead box P3 (FOXP3) gene, a master regulator gene of Treg cells, on ACR severity in liver transplant (LT) recipients. In total, 102 living donor LT patients were enrolled in this study and categorized into no rejection (n = 86), steroid-sensitive acute rejection (SSAR; n = 11), and steroid-resistant acute rejection (SRAR; n = 5). FOXP3 SNPs -3499 A/G (rs3761547), -3279 A/C (rs3761548), and -924 A/G (rs2232365) were genotyped using the polymerase chain reaction restriction fragment length polymorphism technique. T-cell responses to allostimulation were evaluated by the mixed lymphocyte reaction assay. We found no statistical association between the FOXP3 SNP genotype frequencies and ACR incidence. However, significantly higher incidence of SRAR was observed in LT patients with the FOXP3 rs3761548 A/C+A/A genotype than in those with the C/C genotype (A/C+A/A versus C/C; no rejection, SSAR, SRAR, 85.71%, 0%, 14.29% versus 83.58%, 16.42%, 0%, respectively; P = 0.0005). The mixed lymphocyte reaction assay performed at the time of ACR diagnosis showed higher anti-donor CD4+ T-cell responses in patients carrying rs3761548 A/C+A/A than in those with the C/C genotype (P = 0.019). No significant association was observed between the incidence of SRAR and either rs3761547A/G or rs2232365 A/G. Infectious complications and overall survival were not related to FOXP3 SNPs. Conclusion: Our findings indicate that FOXP3 SNP rs3761548 A/C might be a predisposing factor for SRAR after liver transplantation. (Hepatology Communications 2017;1:406-420).

Effect of Fc-γ Receptor Polymorphism on Rituximab-Mediated B Cell Depletion in ABO-Incompatible Adult Living Donor Liver Transplantation.

BACKGROUND: The affinity of IgG Fc receptor (FcγR) for rituximab, an anti-CD20 IgG1, differs based on single-nucleotide polymorphisms (SNPs) in FcγRs. This study aimed to explore the effect of such SNPs on clinical response to rituximab and outcomes in patients of ABO-incompatible (ABOi) living donor liver transplantation (LDLT). METHODS: SNPs of FCGR2A[131H/R] and FCGR3A[158F/V], alleles encoding FcγR, were identified in 20 patients desensitized with rituximab before ABOi LDLT. The effect of these SNPs on B cell elimination and outcomes was analyzed in the patients. RESULTS: The isoform encoded by FCGR2A[131H/H] had a higher affinity for IgG1, and accordingly, the effects of rituximab on B cells were more profound in individuals with FCGR2A[131H/H] than in individuals with FCGR2A[131H/R or R/R]. Specifically, the time to B-cell reappearance in the peripheral blood was significantly delayed, and total serum IgM levels were significantly lower early after LDLT in individuals with FCGR2A[131H/H], even though these SNPs did not significantly affect the reduction of antiblood group A/B antibodies. The incidence of blood stream infection was also significantly higher in individuals with FCGR2A[131H/H], and this SNP was associated with poor prognosis. Despite no significant effect of FCGR3A[158F/V] on survival after ABOi liver grafts, the incidence of infection was significantly higher in individuals with FCGR3A[158F/V or F/F] than in individuals with FCGR3A[158V/V]. CONCLUSIONS: Our findings indicate FCGR SNPs influence the effect of rituximab on B-cell depletion and are possibly predisposing factors for infectious complications after ABOi LDLT. This study will be a good foundation for further studies on larger cohorts.