Successful Sequential Liver and Isolated Intestine Transplantation for Mitochondrial Neurogastrointestinal Encephalopathy Syndrome: A Case Report.

BACKGROUND Mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE) is an autosomal recessive disease caused by thymidine phosphorylase deficiency leading to progressive gastrointestinal dysmotility, cachexia, ptosis, ophthalmoparesis, peripheral neuropathy and leukoencephalopathy. Although liver transplantation corrects thymidine phosphorylase deficiency, intestinal deficiency of the enzyme persists. Retrospective chart review was carried out to obtain clinical, biochemical, and pathological details. CASE REPORT We present a case of liver and subsequent intestine transplant in a 28-year-old man with MNGIE syndrome with gastrointestinal dysmotility, inability to walk, leukoencephalopathy, ptosis, cachexia, and elevated serum thymidine. To halt progression of neurologic deficit, he first received a left-lobe partial liver transplantation. Although his motor deficit improved, gastrointestinal dysmotility persisted, requiring total parenteral nutrition. After exhaustive intestinal rehabilitation, he was listed for intestine transplantation. Two-and-half years after liver transplantation, he received an intestine transplant. At 4 years after LT and 20 months after the intestine transplant, he remains off parenteral nutrition and is slowly gaining weight. CONCLUSIONS This is the first reported case of mitochondrial neurogastrointestinal encephalomyopathy to undergo successful sequential liver and intestine transplantation.

Vascular thrombosis after pediatric liver transplantation: Is prevention achievable?

Background: Vascular thromboses (VT) are life-threatening events after pediatric liver transplantation (LT). Single-center studies have identified risk factors for intra-abdominal VT, but large-scale pediatric studies are lacking. Methods: This multicenter retrospective cohort study of isolated pediatric LT recipients assessed pre- and perioperative variables to determine VT risk factors and anticoagulation-associated bleeding complications. Results: Within seven postoperative days, 31/331 (9.37%) patients developed intra-abdominal VT. Open fascia occurred more commonly in patients with VT (51.61 vs 23.33%) and remained the only independent risk factor in multivariable analysis (OR = 2.84, p = 0.012). Patients with VT received more blood products (83.87 vs 50.00%), had significantly higher rates of graft loss (22.58 vs 1.33%), infection (50.00 vs 20.60%), and unplanned return to the operating room (70.97 vs 16.44%) compared to those without VT. The risk of bleeding was similar (p = 0.2) between patients on and off anticoagulation. Conclusions: Prophylactic anticoagulation did not increase bleeding complications in this cohort. The only independent factor associated with VT was open fascia, likely a graft/recipient size mismatch surrogate, supporting the need to improve surgical techniques to prevent VT that may not be modifiable with anticoagulation.

Deceased Donor Flush Volume Similar for Histidine-Tryptophan-Ketoglutarate and University of Wisconsin at a Single US Organ Procurement Organization: Adult and Pediatric Data.

BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) solutions are the two primary solid-organ preservation solutions used in the United States (>95%), but flush volumes vary markedly by region and center. This study analyzes data from a single organ procurement organization (OPO) to determine the actual clinical flush volumes used for HTK and UW for liver and pancreas grafts. METHODS: All procurements at Indiana Donor Network were analyzed (2016-2020), and data were extracted from the on-site records. Variables included procuring center, solution, volumes, and vessels flushed. Brand and generic versions were considered equivalent. No clinical transplant outcomes were available. RESULTS: Data were analyzed from 875 liver and 192 pancreas procurements by over 70 U.S. centers representing 10 of 11 UNOS regions. The large majority of liver grafts were preserved with HTK (n=810, 93%; UW n=93, 7%). All liver donors received an aortic flush (100%), while portal vein flush was 14% in-situ and 88% back table. For liver grafts, the median volume of infused solution was less for HTK when compared to UW (4225mL vs 5500mL, p=0.04). For pancreas procurement, 100% received aortic flush of the graft, with median HTK and UW volumes being equivalent (3000mL; p=0.85). Pediatric organs were flushed with markedly higher weight-based volumes. CONCLUSIONS: Flush volumes for HTK and UW are similar at one midwestern OPO, with data comprised of procurements performed by centers from across the U.S. These data demonstrate that low-volume HTK flush is commonly used, and this practice may be considered as a cost-saving measure.

Comparative analysis of whole vs. split liver transplantation in infants.

BACKGROUND: Liver transplantation (LT) in infants can be challenging due to their small size and small vasculature. Although both whole LT (WLT) and split LT (SLT) have been described in infants, the head-to-head comparison of these techniques in this population is sparse. METHODS: We retrospectively analyzed the records of all patients with age ≤1 year at Indiana University between 2016 and 2022. All SLT were left lateral segment grafts split in situ. RESULTS: A total of 24 infants were transplanted, with 11 SLT and 13 WLT. The median follow-up time was 52.1 months. Donor and recipient characteristics were comparable except for donor age (19 years vs. 2 years; p < .01) and weight (64 kg vs. 14.2 kg; p < .01). Early allograft dysfunction, primary nonfunction, and hepatic artery thrombosis developed more frequently in the WLT group. There were no biliary complications. There were two early deaths (2 and 4 days) in the WLT group. One-year graft survival (100% vs. 77%; p = .10) and patient survival (100% vs. 85%; p = .18) were numerically higher in the SLT group. CONCLUSIONS: SLT with LLS offers a safe and viable option for liver transplantation in infants and is associated with a trend toward superior outcomes. SLT should be considered as a strategy to reduce waitlist times for infants in the absence of small, deceased donors for WLT.

Simultaneous Heart-kidney Transplant With Planned Delayed Implantation of the Kidney Graft After Ex Vivo Perfusion.

BACKGROUND: Simultaneous heart-kidney transplant (SHK) is an established option for patients with severe heart failure and chronic kidney disease. Recent studies in simultaneous liver-kidney transplantation demonstrate favorable outcomes achieved by delaying implantation of the kidney for over 24 h. This report describes a case series of consecutive patients listed for SHK who had planned delayed implantation of the kidney graft. METHODS: This case series represents a retrospective analysis of SHK patients extracted from the transplant database at a single center. RESULTS: There were 7 patients who underwent SHK during the study period. In all cases, kidney grafts were maintained on hypothermic ex vivo pulsatile perfusion for delayed implantation (mean cold ischemia 53 h [range, 31-69]). The first 5 patients had 100% 1-y heart and kidney graft survival with good function. Patient 6 was unstable on extracorporeal membrane oxygenation post-heart transplant. The kidney was implanted at 69 h, and the patient died soon thereafter. Patient 7 was also unstable on extracorporeal membrane oxygenation after heart transplant. The decision was made to implant the kidney into a backup kidney recipient. The heart transplant recipient subsequently died several days later, whereas the kidney was successfully transplanted in the alternate candidate. CONCLUSIONS: This case series highlights the potential utility of delayed kidney implantation in SHK patients. SHK with delayed renal transplant may provide an improved physiologic environment for renal transplant, which may result in improved early renal graft function. Delayed kidney transplant also provides the opportunity to transplant the kidney graft into an alternate candidate.

Pleural Effusion and Malnutrition Are Associated With Worse Early Outcomes After Liver Transplant.

INTRODUCTION: Pulmonary complications after liver transplantation (LT) have previously been associated with longer hospital stays and ventilator time, and higher mortality. This study reports the outcomes for a specific pulmonary complication, pleural effusion, in LT recipients. METHODS: Records from a single transplant center were analyzed retrospectively for all adult LT patients. Patients with documented pleural effusion by radiographic imaging within 30 days pre- or post-transplant were considered as cases. Outcomes included length of hospital stay, discharge disposition, hospital readmission, discharge with home oxygen, and 1-year survival. RESULTS: During the 4-year study period, 512 LTs were performed, with 107 patients (21%) developing a peri-transplant pleural effusion. In total, 49 patients (10%) had a pre-transplant effusion, 91 (18%) had a post-transplant effusion, and 32 (6%) had both. Characteristics associated with the presence of any pleural effusion included an increasing model for end-stage liver disease score, re-transplantation, diagnosis of alcoholic liver disease, low protein levels, and sarcopenia. Effusion patients had longer hospital stays (17 vs 9 days, P < .001) and higher likelihood of discharge to a care facility (48% vs 21%, P < .001). Ninety-day readmission occurred in 69% of effusion patients (vs 44%, P < .001). One-year patient survival with any effusion was 86% (vs 94%, P < .01). CONCLUSIONS: Overall, 21% of recipients developed a clinically significant peri-transplant pleural effusion. Pleural effusion was associated with worse outcomes for all clinical measures. Risk factors for the development of pleural effusion included higher MELD score (>20), re-transplantation, alcoholic liver disease, and poor nutrition status, including poor muscle mass.

Critical Care and Mechanical Ventilation Practices Surrounding Liver Transplantation in Children: A Multicenter Collaborative.

OBJECTIVES: We aimed to determine which characteristics and management approaches were associated with postoperative invasive mechanical ventilation (IMV) and with a prolonged course of IMV in children post liver transplant as well as describing the utilization of critical care resources. DESIGN: Retrospective, multicenter, cohort study of children who underwent an isolated liver transplantation between January 2017 and December 2018. SETTING: Twelve U.S., pediatric, liver transplant centers. PATIENTS: Three hundred thirty children post liver transplant admitted to the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Six patients died in our cohort. The median length of PICU stay was 4.5 days (interquartile range [IQR], 2.9-8.2 d). Most patients were initially monitored with arterial catheters (96%), central venous pressures (95%), and liver ultrasound (93%). Anticoagulation (80%), blood product administration (52.4%), and vasoactive agents (23.0%) were commonly used therapies in the first 7 days. In multivariable logistic regression analysis, age (adjusted odds ratio [aOR] 0.9 [0.86-0.95]), open fascia (aOR 7.0 [95% CI, 2.6-18.9]), large center size (aOR 4.3 [95% CI 2.2-8.3]), and higher Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease scores (aOR 1.04 [95% CI, 1.01-1.06]) were associated with postoperative IMV. In multivariable logistic regression analysis, postoperative day 0 peak inspiratory pressure (PIP) (aOR 1.2 [95% CI, 1.1-1.3]), large center size (aOR 2.9 [95% CI, 1.6-5.4]), and age (aOR 0.89 [95% CI, 0.85-0.95]) were associated with length of IMV greater than 24 hours. Length of IMV greater than 24 hours was associated with bleeding complications ( p = 0.03), infections ( p = 0.03), graft loss ( p = 0.02), and reoperation ( p = 0.03). CONCLUSIONS: Younger age, preoperative hospitalization, large center size, and open fascia are associated with use of IMV, and younger age, large center size, and postoperative day 0 PIP are associated with prolonged IMV on multivariable analysis. Longer IMV is associated with negative outcomes, making it an important clinical marker.

Hepatic Ischemia/Reperfusion Injury After Liver Transplantation Is Not Associated with Early Impairment of Left Ventricular Ejection Fraction.

BACKGROUND Early myocardial dysfunction is a known complication following liver transplant. Although hepatic ischemia/reperfusion injury (hIRI) has been shown to cause myocardial injury in rat and porcine models, the clinical association between hIRI and early myocardial dysfunction in humans has not yet been established. We sought to define this relationship through cardiac evaluation via transthoracic echocardiography (TTE) on postoperative day (POD) 1 in adult liver transplant recipients. MATERIAL AND METHODS TTE was performed on POD1 in all liver transplant patients transplanted between January 2020 and April 2021. Hepatic IRI was stratified by serum AST levels on POD1 (none: <200; mild: 200-2000; moderate: 2000-5000; severe: >5000). All patients had pre-transplant TTE as part of the transplant evaluation. RESULTS A total of 173 patients underwent liver transplant (LT) between 2020 and 2021 and had a TTE on POD 1 (median time to echo: 1 day). hIRI was present in 142 (82%) patients (69% mild, 8.6% moderate, 4% severe). Paired analysis between pre-LT and post-LT left ventricular ejection fraction (LVEF) of the entire study population demonstrated no significant decrease following LT (mean difference: -1.376%, P=0.08). There were no significant differences in post-LT LVEF when patients were stratified by severity of hIRI. Three patients (1.7%) had significant post-transplant impairment of LVEF (<35%). None of these patients had significant hIRI. CONCLUSIONS hIRI after liver transplantation is not associated with immediate reduction in LVEF. The pathophysiology of post-LT cardiomyopathy may be driven by extra-hepatic triggers.

Liver Transplantation in Recipients With Class III Obesity: Posttransplant Outcomes and Weight Gain.

BACKGROUND: There has been a dramatic increase in obesity in the United States. Several studies have reported conflicting results for the impact of obesity on outcomes of liver transplantation (LT). This study aims to assess the impact of obesity on LT and changes in body mass index (BMI) after transplantation. METHODS: All adult LTs performed at Indiana University between 2001 and 2018 were reviewed. BMIs of recipients were subdivided into 6 categories. Survival outcomes were compared across the subgroup. BMI was followed up in a cohort of patients from 2008 to 2018. RESULTS: Among 2024 patients, 25% were in class I obesity, 9.3% were in class II obesity, and 1.1% were in class III obesity. There was no significant difference in patient and graft survival at 10-y follow-up with respect to BMI. Among 1004 patients in the subgroup, BMI of all groups except the underweight group declined in the first 3 mo postoperatively; however, the BMI of all groups except the class III obesity group returned to the pre-LT level by 2 y and reached a plateau by 5 y. In the class III obesity group, there was a significant increase in body weight at 5 y. CONCLUSIONS: Class III obesity was not associated with higher mortality in our cohort. Because our cohort is small, it may be underpowered to detect a smaller difference in outcome. From our observation, obesity should not be considered a contraindication for LT. Post-LT interventions are required to prevent significant weight gain for the class III obesity group.

Impact of the acuity circle model for liver allocation on multivisceral transplant candidates.

Liver allocation was updated on February 4, 2020, replacing a Donor Service Area (DSA) with acuity circles (AC). The impact on waitlist outcomes for patients listed for combined liver-intestine transplantation (multivisceral transplantation [MVT]) remains unknown. The Organ Procurement and Transplantation Network/United Network for Organ Sharing database was used to identify all candidates listed for both liver and intestine between January 1, 2018 and March 5, 2021. Two eras were defined: pre-AC (2018-2020) and post-AC (2020-2021). Outcomes included 90-day waitlist mortality and transplant probability. A total of 127 adult and 104 pediatric MVT listings were identified. In adults, the 90-day waitlist mortality was not statistically significantly different, but transplant probability was lower post-AC. After risk-adjustment, post-AC was associated with a higher albeit not statistically significantly different mortality hazard (sub-distribution hazard ratio[sHR]: 8.45, 95% CI: 0.96-74.05; p = .054), but a significantly lower transplant probability (sHR: 0.33, 95% CI: 0.15-0.75; p = .008). For pediatric patients, waitlist mortality and transplant probability were similar between eras. The proportion of patients who underwent transplant with exception points was lower post-AC both in adult (44% to 9%; p = .04) and pediatric recipients (65% to 15%; p = .002). A lower transplant probability observed in adults listed for MVT may ultimately result in increased waitlist mortality. Efforts should be taken to ensure equitable organ allocation in this vulnerable patient population.

Combined liver-kidney transplantation with positive crossmatch: Role of delayed kidney transplantation.

BACKGROUND: Positive crossmatch (XM+) combined liver-kidney transplantation due to preformed donor-specific human leukocyte antigen antibodies has produced mixed results. We sought to understand the role of delayed kidney transplant approach in XM+ combined liver-kidney transplantations. METHODS: XM+ combined liver-kidney transplantations were retrospectively reviewed. T- and B-cell XM, complement-dependent cytotoxic crossmatch, and flow cytometric crossmatch were performed prospectively. RESULTS: Of 183 combined liver-kidney transplantations performed (2002-2019), 114 (62%) were with "delayed" kidney transplant approach and 19 (19 of 183, 10%) were XM+. Of 19 XM+ combined liver-kidney transplantations, kidney transplant was "delayed" in 14 by an average of 47 hours (range 24-64 hours) from liver transplant. There was a significant reduction in both class I (mean pre-liver transplant mean fluorescence intensity (MFI) 26,230 versus mean post-liver transplant and pre-delayed kidney transplant MFI 3,272, P = .01) and total MFI (mean pre-liver transplant MFI 27,233 vs mean post liver transplant and predelayed kidney transplant MFI 11,469, P = .01). However, there was no significant change in the MFI of class II donor-specific antibodies (mean pre-liver transplant MFI 17,899 versus post-liver transplant and pre-delayed kidney transplant MFI 14,341, P = .19). None of XM+ delayed kidney transplants had delayed graft function, and there was no antibody-mediated rejection. One-year patient survival for the XM+ combined liver-kidney transplantation with delayed kidney transplant approach was 92.9%, which is comparable to patient survival of XM- combined liver-kidney transplantation. Whereas patient survival in recipients before "delayed" approach ("simultaneous"; n = 5) was 40% when liver-kidney transplants were performed simultaneously (P = .06). CONCLUSION: In sensitized combined liver-kidney transplantation recipients, the "delayed" kidney transplant approach is associated with a significant reduction in total and class I donor-specific antibodies after liver transplant before kidney transplant, enabling therapeutic interventions such as plasmapheresis, if needed, providing optimal outcomes similar to crossmatch recipients.

Distal allograft pancreatectomy for graft salvage after pancreas transplantation.

Early pancreas allograft failure most commonly results from vascular thrombosis. Immediate surgical intervention may permit pancreas allograft salvage, typically requiring thrombectomy. In cases of partial allograft necrosis secondary to splenic arterial thrombosis, distal allograft pancreatectomy may allow salvage of at least half of the pancreas allograft with retention of function. We retrospectively reviewed four cases of simultaneous pancreas and kidney recipients who required distal allograft pancreatectomy for splenic artery thrombosis with necrosis of the distal pancreas. Three of the four maintained long-term allograft function with euglycemia independent of insulin at six months to six years of follow-up, and all patients continue to maintain normal renal allograft function. Early diagnosis and early intervention are essential in order to salvage the pancreas allograft in the case of thrombosis. Distal allograft pancreatectomy can be performed safely and result in excellent long-term outcomes in select patients.

Donor-recipient body size mismatch has no impact on outcomes after deceased donor whole liver transplantation: Role of donor liver size measurement.

The role of donor-recipient body size mismatch (DRSM) on outcomes after whole liver transplantation (LT) is not clearly defined. At our center, in presence of considerable DRSM, objective assessment of the donor liver by a radiology or intraoperative evaluation by procuring surgeon was incorporated. To evaluate the impact of DRSM on graft outcomes with this approach, adult deceased donor whole liver transplants between July 2001 and December 2017 at our center were studied. DRSM was considered when the donor-recipient body surface area (BSA) ratio (DR-BSAr) was either <0.69 or >1.25. There were 54 (3.2%) transplants with DR-BSAr <0.69 and 61 (3.6%) with DR-BSAr >1.25. One-year graft survival was 85% vs. 89% vs. 89%; (p = .64) for transplants with DR-BSArs of <0.69, 0.69-1.25, and >1.25, respectively. Early allograft dysfunction (EAD) (28% vs. 27% vs. 37%; p = .07), post-transplant coagulopathy, bilirubinemia, and renal function were also comparable. In conclusion, with the actual measurement of the donor liver and recipient abdominal cavity, significant DRSM did not have a negative impact on early and long-term outcomes. Routine measurement of donor liver size by radiology may be incorporated in liver allocation to improve utilization.

Practice variation in the immediate postoperative care of pediatric liver transplant patients: Framework for a national consensus.

Advancements in critical care management have led to improvement in pediatric LT outcomes. However, there are no specific guidelines for many aspects of immediate post-LT care. This survey examines practice variations in the immediate postoperative care of pediatric LT patients at a large number of active US centers. This study is a cross-sectional survey of medical directors at PALISI-affiliated PICU in the United States. Centers performing pediatric LT were analyzed. Study measures included PICU practices regarding staffing, composition of the multidisciplinary team, early post-LT graft and patient monitoring, and anticoagulation. Of the thirty-five responding centers, twenty-five had a LT program which accounted for one-half of all US pediatric LTs. For analysis, centers were categorized by volume: high (7), medium (11), and low (7). The majority of PICU teams included an intensivist (80%) and hepatologist (84%). High-volume centers were less likely to have 24-hour in-house attending coverage (29%, compared to 64% (medium) and 100% (low)). High-volume centers were most likely to have pre-printed orders, but least likely to have written PICU management protocols. Most centers utilize routine daily liver ultrasound. Routine prophylactic anticoagulation, and the agent of choice, was variable. There is marked inconsistency in post-LT practice across PALISI centers in regards to team composition and immediate post-LT management. A national US consensus for post-LT PICU practices would facilitate outcomes research and would establish a platform for multicenter studies.

CAD-LT score effectively predicts risk of significant coronary artery disease in liver transplant candidates.

BACKGROUND & AIMS: Patients with cirrhosis and significant coronary artery disease (CAD) are at risk of peri-liver transplantation (LT) cardiac events. The coronary artery disease in liver transplantation (CAD-LT) score and algorithm aim to predict the risk of significant CAD in LT candidates and guide pre-LT cardiac evaluation. METHODS: Patients who underwent pre-LT evaluation at Indiana University (2010-2019) were studied retrospectively. Stress echocardiography (SE) and cardiac catheterization (CATH) reports were reviewed. CATH was performed for predefined CAD risk factors, irrespective of normal SE. Significant CAD was defined as CAD requiring percutaneous or surgical intervention. A multivariate regression model was constructed to assess risk factors. Receiver-operating curve analysis was used to compute a point-based risk score and a stratified testing algorithm. RESULTS: A total of 1,771 pre-LT patients underwent cardiac evaluation, including results from 1,634 SE and 1,266 CATH assessments. Risk-adjusted predictors of significant CAD at CATH were older age (adjusted odds ratio 1.05; 95% CI 1.03-1.08), male sex (1.69; 1.16-2.50), diabetes (1.57; 1.12-2.22), hypertension (1.61; 1.14-2.28), tobacco use (pack years) (1.01; 1.00-1.02), family history of CAD (1.63; 1.16-2.28), and personal history of CAD (6.55; 4.33-9.90). The CAD-LT score stratified significant CAD risk as low (≤2%), intermediate (3% to 9%), and high (≥10%). Among patients who underwent CATH, a risk-based testing algorithm (low: no testing; intermediate: non-invasive testing vs. CATH; high: CATH) would have identified 97% of all significant CAD and potentially avoided unnecessary testing (669 SE [57%] and 561 CATH [44%]). CONCLUSIONS: The CAD-LT score and algorithm (available at www.cad-lt.com) effectively stratify pre-LT risk for significant CAD. This may guide more targeted testing of candidates with fewer tests and faster time to waitlist. LAY SUMMARY: The coronary artery disease in liver transplantation (CAD-LT) score and algorithm effectively stratify patients based on their risk of significant coronary artery disease. The CAD-LT algorithm can be used to guide a more targeted cardiac evaluation prior to liver transplantation.

Incisional Hernia After Orthotopic Liver Transplantation: A Systematic Review and Meta-analysis.

BACKGROUND: Incisional hernia (IH) is a well-known complication of orthotopic liver transplantation. Despite wide recognition of the impact of this problem, the incidence remains imprecisely known. METHODS: The MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials and Cochrane Database of Systematic Reviews databases were searched from their inception to November 2017 for abstracts documenting IH after orthotropic liver transplantation (OLT). The primary endpoint of this study was incidence of IH, secondary endpoints were time to hernia and recurrence. Three reviewers independently graded abstracts for inclusion in this review. Heterogeneity in combining data was assumed prior to pooling. Random-effects meta-analyses were performed to estimate percentages and 95% CIs. RESULTS: After a review of 77 abstracts, 18 studies were graded as relevant. The methodological quality of studies was assessed with a minimum Oxford Centre for Evidence-Based Medicine level of 2B. These represent a cohort of 981 patients with IH after OLT reported in the literature. A meta-analysis of studies meeting inclusion criteria shows mean incidence of 15.1% (CI 12.1%-18.2%). Aggregate recurrence rate reported in the literature is 12.4% (CI 4.3%-20.5%). Overall reported time to IH after OLT was 42.9 months. CONCLUSIONS: Although reported incidences of IH after OLT vary widely across studies, an overall incidence of 15.1% is reported. This is a relatively late complication after transplantation. Recurrence of hernia after initial repair is 12.4% within this patient population.