N. Thao N. Galvan

Liver transplant length of stay (LOS) index: A novel predictive score for hospital length of stay following liver transplantation

An index to predict hospital length of stay after liver transplantation could address unmet clinical needs. Length of stay is an important surrogate for hospital costs and efforts to limit stays can preserve our healthcare resources. Here, we devised a scoring system that predicts hospital length of stay following liver transplantation. We used univariate and multivariate analyses on 73 635 adult liver transplant recipient data and identified independent recipient and donor risk factors for prolonged hospital stay (>30 days). Multiple imputation was used to account for missing variables. We identified 22 factors as significant predictors of prolonged hospital stay, including the most significant risk factors: intensive care unit (ICU) admission (OR 1.75, CI 1.58‐1.95) and previous transplant (OR 1.60, CI 1.47‐1.75). The length of stay (LOS) index assigns weighted risk points to each significant factor in a scoring system to predict prolonged hospital stay after liver transplantation with a c‐statistic of 0.75. The LOS index demonstrated good discrimination across the entire population, dividing the cohort into tertiles, which had odds ratios of 2.25 (CI 2.06‐2.46) and 7.90 (7.29‐8.56) for prolonged hospital stay (>30 days). The LOS index utilizes 22 significant donor and recipient factors to accurately predict hospital length of stay following liver transplantation. The index further demonstrates the basis for a clear clinical recommendation to mitigate risk of long hospitalization by minimizing cold ischemia time.

Profiling immunologic risk for acute rejection in liver transplantation: Recipient age is an important risk factor

BACKGROUND Careful management of induction and maintenance of immunosuppression is paramount to prevent acute rejection in liver transplantation. A methodical analysis of risk factors for acute cellular rejection may provide a more comprehensive method to profile the immunologic risk of candidates. METHODS Using registry data from the Organ Procurement and Transplantation Network (OPTN), we identified 42,508 adult recipients who underwent orthotopic liver transplant (OLT) between 2002 and 2013. We excluded recipients with a blank entry for treated rejection. We analyzed this all inclusive cohort in addition to a subset of 27,493 patients with just tacrolimus immunosuppression. Multivariate logistic regression was used on both cohorts and identified independent risk factors for treated acute rejection at one year. RESULTS Recipient age (reference group was 40 to 60years) was a dominant risk factor for rejection in both cohorts and had a dose response relationship. The strongest risk factors in the inclusive cohort were: age 18-25 (OR 2.20), age 26-29 (OR 2.03), and primary biliary cholangitis (OR 1.55). The most protective factors were age 70 and older (OR 0.68), and age 65-69 (OR 0.70). The rates of rejection had a similar pattern. CONCLUSIONS Although prior studies have suggested age as a risk factor for rejection in liver transplantation, this is the first study of national-level data to demonstrate a robust dose dependent relationship between age and risk for rejection at one year. Clinicians should place significant weight on recipient age when they assess their recipients for the immunologic risk of rejection.

Portosystemic shunt as a bridge to liver transplantation in infants: A comparison of two techniques

Portosystemic shunts can serve as a bridge to liver transplantation in patients with end‐stage liver disease by providing portal decompression to treat life‐threatening variceal bleeding and prevent recurrent episodes until an organ becomes available. The conventional TIPS procedure, however, is technically challenging to perform in infants due to the small size of their intrahepatic vasculature. We report two cases of emergent creation of portosystemic shunts as a bridge to liver transplantation in infants with life‐threatening variceal bleeding using a conventional TIPS technique in the first case and a percutaneous DIPS technique in the other. Both procedures were successful at reducing the portosystemic pressure gradient and preventing further variceal bleeds until a liver transplant could be performed. The novel percutaneous DIPS procedure is a valuable alternative to the conventional TIPS in infants, as it is better suited for small or challenging intrahepatic vascular anatomy.

Are drowned donors marginal donors? A single pediatric center experience

Drowning, a common cause of death in the pediatric population, is a potentially large donor pool for OLT. Anecdotally, transplant centers have deemed these organs high risk over concerns for infection and graft dysfunction. We theorized drowned donor liver allografts do not portend worse outcomes and therefore should not be excluded from the donation pool. We reviewed our single‐center experience of pediatric OLTs between 1988 and 2015 and identified 33 drowned donor recipients. These OLTs were matched 1:2 to head trauma donor OLTs from our center. A chart review assessed postoperative peak AST and ALT, incidence of HAT, graft and recipient survival. Recipient survival at one year between patients with drowned donor vs head trauma donor allografts was not statistically significant (94% vs 97%, P=.63). HAT incidence was 6.1% in the drowned donor group vs 7.6% in the control group (P=.78). Mean postoperative peak AST and ALT was 683 U/L and 450 U/L for drowned donors vs 1119 U/L and 828 U/L in the matched cohort. These results suggest drowned donor liver allografts do not portend worse outcomes in comparison with those procured from head trauma donors.

Liver transplantation as definitive treatment of an unresectable mesenchymal hamartoma in a child with Beckwith–Wiedemann Syndrome

Abstract Mesenchymal liver hamartomas are benign tumors that can cause life-threatening abdominal distension and carry a risk for malignant transformation. In this case report, we describe a 13-month-old male with Beckwith–Wiedemann Syndrome (BWS) who presented with multiple mesenchymal liver hamartomas causing severe intra-abdominal mass effect. Imaging revealed six large multi-locular cystic lesions, ranging from 3.8 to 8.9 cm in diameter. The large size and spread of the tumors necessitated liver transplantation for complete removal. The patient successfully underwent cadaveric piggyback liver transplantation at 25 months of age. He was alive at 16-month follow-up without evidence of tumor recurrence or graft rejection. Histological examination of the hepatic masses revealed mucinous epithelial lining and abundant hepatocytes in varying stages of differentiation, supporting the diagnosis of mesenchymal hamartoma. To the best of our knowledge, this is the first reported case of liver transplantation in a patient with BWS as definitive treatment for unresectable mesenchymal liver hamartoma.

No Child Left Behind: Liver Transplantation in Critically Ill Children

BACKGROUND Advances in critical care prolong survival in children with liver failure, allowing more critically ill children to undergo orthotopic liver transplantation (OLT). In order to justify the use of a scarce donor resource and avoid futile transplants, we sought to determine survival in children who undergo OLT while receiving pre-OLT critical care. STUDY DESIGN We analyzed 13,723 pediatric OLTs using the United Network for Organ Sharing (UNOS) database from 1987 to 2015, including 6,746 recipients in the Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease (MELD/PELD) era (2002 to 2015). There were 1,816 recipients (26.9%) admitted to the ICU at the time of transplantation. We also analyzed 354 pediatric OLT recipients at our center from 2002 to 2015, one of the largest institutional experiences. Sixty-five recipients (18.3%) were admitted to the ICU at the time of transplantation. Kaplan-Meier, volume threshold, and multivariable analyses were performed. RESULTS Patient survival improved steadily over the study period, (66% 1-year survival in 1987 vs 92% in 2015; p < 0.001). Our institutional experience of ICU recipients in the MELD/PELD era had acceptable outcomes (87% 1-year survival), even among our sickest recipients with vasoactive medications, mechanical ventilation, dialysis, and molecular adsorbent recirculating system requirements. Volume analysis revealed inferior outcomes (hazard ratio [HR] 1.68; 95% CI 1.11 to 2.51) in low-volume centers (<5 annual cases). Identifiable risk factors (previous transplantation, elevated serum sodium, hemodialysis, mechanical ventilation, body weight < 6 kg, and low center volume) increased risk of mortality. CONCLUSIONS This analysis demonstrates that the use of advanced critical care in children and infants with liver failure is justified because OLT can be performed on the sickest children and acceptable outcomes achieved. It is an appropriate use of a scarce donor allograft in a child who would otherwise succumb to a terminal liver disease.

Celiac Axis Extension Grafts in Orthotopic Liver Transplantation

The arterial reconstruction during orthotopic liver transplantation (OLT) is often the most challenging aspect of the procedure that must be achieved. This is due to the wide range of diversity in donor and recipient vasculature including poor arterial perfusion, arterial dissection, complex anatomy, mycotic aneurysms, difficulty in arterial mobilization, adhesions, and others.(1,2) The use of aortic conduits, specifically infrarenal, supraceliac, and others, has been demonstrated to overcome the difficulties in arterial reconstruction and to avoid hepatic artery thrombosis (HAT). Despite an alteration to the normal arterial anatomy, successful longterm outcomes have been achieved for many. However, the procedure requires clamping of the aorta and has been reported to increase the risk of postoperative morbidity and mortality in a number of recipients. HAT is one of the most feared complications because of subsequent high rates of allograft failure, need for retransplant, and patient mortality. Bekker et al.(3) reported in their systematic review an average 1-year graft survival close to 50% in patients diagnosed with HAT within 1 month of transplant. Other significant aortohepatic conduit complications in adults and children include biliary complications (ischemic cholangiopathy), bowel obstruction, recipient paralysis, aneurysm formation, and prolonged ventilation.(1) Although previous literature has shown various graft sources as solutions to vasculature issues during transplant, our current report focuses on cases in which the arterial flow was felt to be inadequate following the initial hepatic arterial anastomosis. Therefore, the celiac axis was maintained as the source of arterial inflow and a donor iliac artery graft was used (Fig. 1). The donor iliac artery was anastomosed to the recipient celiac axis to achieve sufficient vessel length, to remove unfavorable arterial vessel segments, and to improve inflow. The donor iliac artery was then anastomosed to the donor celiac axis to complete the arterial reconstruction (Fig. 2). Aortohepatic conduits have been reported to result in inferior outcomes compared with the standard arterial anastomosis.(1) Del Gaudio et al.(4) concluded that in recipients undergoing arterial reconstruction using the donor iliac artery and inflow using the infrarenal aorta, 26% of graft loss was due to HAT. In contrast, the use of the recipient celiac axis allows a source of adequate inflow without the need for excessive aortic dissection, aortic clamping, and disruption in the normal arterial anatomy. Up to this point, the use of donor iliac arterial grafts being placed on the recipient celiac axis has been underused. We characterize the outcomes of patients at our institution who were felt to have inadequate arterial flow following an initial arterial anastomosis without a history of celiac stenosis and who required arterial extension grafts from the recipient celiac axis to the donor celiac axis with patient and allograft survival comparable to the national published values.

Cold ischemia time is an important risk factor for post–liver transplant prolonged length of stay

Risk analysis of cold ischemia time (CIT) in liver transplantation has largely focused on patient and graft survival. Posttransplant length of stay is a sensitive marker of morbidity and cost. We hypothesize that CIT is a risk factor for posttransplant prolonged length of stay (PLOS) and aim to conduct an hour‐by‐hour analysis of CIT and PLOS. We retrospectively reviewed all adult, first‐time liver transplants between March 2002 and September 2016 in the United Network for Organ Sharing database. The 67,426 recipients were categorized by hourly CIT increments. Multivariate logistic regression of PLOS (defined as >30 days), CIT groups, and an extensive list of confounding variables was performed. Linear regression between length of stay and CIT as continuous variables was also performed. CIT 1‐6 hours was protective against PLOS, whereas CIT >7 hours was associated with increased odds for PLOS. The lowest odds for PLOS were observed with 1‐2 hours (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.45‐0.92) and 2‐3 hours (OR, 0.65; 95% CI, 0.55‐0.78) of CIT. OR for PLOS steadily increased with increasing CIT, reaching the greatest odds for PLOS with 13‐14 hours (OR, 2.05; 95% CI, 1.57‐2.67) and 15‐16 hours (OR, 2.06; 95% CI, 1.27‐3.33) of CIT. Linear regression revealed a positive correlation between length of stay and CIT with a correlation coefficient of +0.35 (P < 0.001). In conclusion, post–liver transplant length of stay is sensitive to CIT, with a substantial increase in the odds of PLOS observed with nearly every additional hour of cold ischemia. We conclude that CIT should be minimized to protect against the morbidity and cost associated with posttransplant PLOS. Liver Transplantation 24 762–768 2018 AASLD.

Mending a Broken Heart: Treatment of Stress-Induced Heart Failure after Solid Organ Transplantation

Stress-induced heart failure, also known as Broken Heart Syndrome or Takotsubo Syndrome, is a phenomenon characterized as rare but well described in the literature, with increasing incidence. While more commonly associated with postmenopausal women with psychiatric disorders, this entity is found in the postoperative patient. The nonischemic cardiogenic shock manifests as biventricular failure with significant decreases in ejection fraction and cardiac function. In a review of over 3000 kidney and liver transplantations over the course of 17 years within two transplant centers, we describe a series of 7 patients with Takotsubo Syndrome after solid organ transplantation. Furthermore, we describe a novel approach of successfully treating the transient, though potentially fatal, cardiogenic shock with a percutaneous ventricular assistance device in two liver transplant patients, while treating one kidney transplant patient medically and the remaining four liver transplant patients with an intra-aortic balloon pump. We describe our experience with Takotsubos Syndrome and compare the three modalities of treatment and cardiac augmentation. Our series is novel in introducing the percutaneous ventricular assist device as a more minimally invasive intervention in treating nonischemic heart failure in the solid organ transplant patient, while serving as a comprehensive overview of treatment modalities for stress-induced heart failure.

Reoperative complications following pediatric liver transplantation

BACKGROUND The aim of this study is to describe the incidence and impact of reoperation following pediatric liver transplantation, as well as the indications and risk factors for these complications. METHODS All primary pediatric liver transplants performed at our institution between January 2012 and September 2016 were reviewed. A reoperative complication was defined as a complication requiring return to the operating room within 30 days or the same hospital admission as the transplant operation, excluding retransplantation. RESULTS Among the 144 pediatric liver transplants performed during the study period, 9% of the recipients required reoperation. The most common indications for reoperation were bleeding and bowel complications. There was no significant difference in the graft survival of patients with a reoperation and those without a reoperation (p = 0.780), but patients with a reoperation had a significantly longer hospital length of stay (median of 39 days vs. 11 days, p = 0.001). Variant donor arterial anatomy, transplant operative time, intraoperative blood loss, transfusion volume of packed red blood cells or cell saver per weight, and transfusion with fresh frozen plasma, platelets, or cryoprecipitate were significantly associated with reoperation upon univariable logistic regression, but none of these risk factors remained statistically significant upon multivariable regression. CONCLUSION At our institution, reoperation did not significantly impact graft survival. We identified variant donor arterial anatomy, transplant operative time, intraoperative blood loss, transfusion volume of packed red blood cells or cell saver per weight, and transfusion with fresh frozen plasma, platelets, or cryoprecipitate as risk factors for reoperation, although none of these risk factors demonstrated independent association with reoperation in a multivariable model. TYPE OF STUDY Prognosis Study. LEVEL OF EVIDENCE Level III.