Safety and Immunogenicity of the mRNA-1273 Coronavirus Disease 2019 Vaccine in Solid Organ Transplant Recipients.

BACKGROUND: Solid organ transplant recipients (SOTRs) are at high risk for severe COVID-19. METHODS: This open-label, phase 3b trial evaluated mRNA-1273 in 137 kidney and 77 liver SOTRs and 20 immunocompetent participants. In part A, SOTRs received three 100-µg doses of mRNA-1273; immunocompetent participants received 2 doses. In part B, an additional 100-µg dose was offered ≥4 months after the primary series. Here, we report interim trial results. RESULTS: mRNA-1273 was well-tolerated in SOTRs. Four serious adverse events were considered vaccine related by the investigator in 3 SOTRs with preexisting comorbidities. No vaccine-related biopsy-proven organ rejection events or deaths were reported. mRNA-1273 elicited modest neutralizing antibody responses after dose 2 and improved responses after dose 3 in SOTRs. Post-dose 3 responses among liver SOTRs were comparable to post-dose 2 responses in immunocompetent participants. Post-additional dose responses were increased in SOTRs, regardless of primary series vaccination. In liver SOTRs, post-additional dose responses were ∼3-fold higher versus post-dose 2 but lower than immunocompetent participant responses. Most kidney SOTRs received multiple immunosuppressants and had reduced antibody responses versus liver SOTRs. CONCLUSIONS: mRNA-1273 was well-tolerated, and dose 3 and the additional dose improved antibody responses among SOTRs. CLINICAL TRIALS REGISTRATION: NCT04860297.

Immunotactoid hepatopathy: A novel entity with histologically proven recurrence post liver transplantation.

Immunotactoid deposition is a rare fibrillary deposition disease that is primarily seen in the kidney and is associated with paraproteinemia. Here, we report a case of hepatic immunotactoid deposition in a 67-year-old male with a history of smoldering myeloma and chronic kidney disease who underwent liver transplantation for metabolic dysfunction-related cirrhosis. Immunotactoid deposition was first identified in the explanted liver and recurred in the allograft within only 7 weeks following transplantation, presenting as ascites with normal liver function tests. The patient's posttransplant course was complicated by proteinuria and renal failure requiring dialysis. Histologic examination of both native and allograft livers demonstrated pink amorphous material occupying sinusoidal spaces that were Congo-red negative and immunoglobulin M Kappa-restricted. Electron microscopy revealed characteristic deposits of electron-dense bundles of hollow microtubules with a 40 nm diameter within the sinusoids and space of Disse, consistent with immunotactoids. Therapy of the patient's underlying plasma-cell dyscrasia utilizing a daratumumab-based regimen showed decreased serum paraproteins, resolution of ascites, and improved kidney function, no longer requiring dialysis, without inducing rejection. The patient continues to respond to treatment 10 months posttransplant.

Ten-year follow-up of cavoportal hemitransposition in pediatric liver transplantation for complete portomesenteric venous thrombosis: A case report and literature review.

BACKGROUND: Portal vein thrombosis is a potentially devastating complication following pediatric liver transplantation. In rare instances of complete portomesenteric thrombosis, cavoportal hemitransposition may provide graft inflow. Here we describe long-term results following a case of pediatric cavoportal hemitransposition during liver transplantation and review the current pediatric literature. METHODS: A 9-month-old female with a history of biliary atresia and failed Kasai portoenterostomy underwent living donor liver transplantation, which was complicated by portomesenteric venous thrombosis. The patient underwent retransplantation with cavoportal hemitransposition on postoperative day 12. OUTCOME: The patient recovered without further complication, and 10 years later, she continues to do well, with normal graft function and no clinical sequelae of portal hypertension. CT scan with 3-D vascular reconstruction demonstrated recanalization of the splanchnic system, with systemic drainage to the inferior vena cava via an inferior mesenteric vein shunt. The cavoportal anastomosis remains patent with hepatopetal flow. Of the 12 previously reported cases of pediatric cavoportal hemitransposition as portal inflow in liver transplantation, this is the longest-known follow-up with a viable allograft. Notably, sequelae of portal hypertension were also rare in the 12 previously reported cases, with no cases of long-term renal dysfunction, lower extremity edema, or ascites. CONCLUSIONS: Long-term survival beyond 10 years with normal graft function is feasible following pediatric cavoportal hemitransposition. Complications related to portal hypertension were generally short-lived, likely due to the development of robust collateral circulation. Additional reports of long-term outcomes are necessary to facilitate informed decision making when considering pediatric cavoportal hemitransposition for liver graft inflow.

Left Lobe First With Purely Laparoscopic Approach: A Novel Strategy to Maximize Donor Safety in Adult Living Donor Liver Transplantation.

OBJECTIVE: Evaluate outcome of left-lobe graft (LLG) first combined with purely laparoscopic donor hemihepatectomy (PLDH) as a strategy to minimize donor risk. BACKGROUND: An LLG first approach and a PLDH are 2 methods used to reduce surgical stress for donors in adult living donor liver transplantation (LDLT). But the risk associated with application LLG first combined with PLDH is not known. METHODS: From 2012 to 2023, 186 adult LDLTs were performed with hemiliver grafts, procured by open surgery in 95 and PLDH in 91 cases. LLGs were considered first when graft-to-recipient weight ratio ≥0.6%. Following a 4-month adoption process, all donor hepatectomies, since December 2019, were performed laparoscopically. RESULTS: There was one intraoperative conversion to open (1%). Mean operative times were similar in laparoscopic and open cases (366 vs 371 minutes). PLDH provided shorter hospital stays, lower blood loss, and lower peak aspartate aminotransferase. Peak bilirubin was lower in LLG donors compared with right-lobe graft donors (1.4 vs 2.4 mg/dL, P < 0.01), and PLDH further improved the bilirubin levels in LLG donors (1.2 vs 1.6 mg/dL, P < 0.01). PLDH also afforded a low rate of early complications (Clavien-Dindo grade ≥ II, 8% vs 22%, P = 0.007) and late complications, including incisional hernia (0% vs 13.7%, P < 0.001), compared with open cases. LLG was more likely to have a single duct than a right-lobe graft (89% vs 60%, P < 0.01). Importantly, with the aggressive use of LLG in 47% of adult LDLT, favorable graft survival was achieved without any differences between the type of graft and surgical approach. CONCLUSIONS: The LLG first with PLDH approach minimizes surgical stress for donors in adult LDLT without compromising recipient outcomes. This strategy can lighten the burden for living donors, which could help expand the donor pool.

Combined Liver Transplant and Cardiac Surgery: Long-Term Outcomes and Predictors of Success.

OBJECTIVE: We aim to report our institutional outcomes of single-staged combined liver transplantation (LT) and cardiac surgery (CS). SUMMARY BACKGROUND DATA: Concurrent LT and CS is a potential treatment for combined cardiac dysfunction and end-stage liver disease, yet only 54 cases have been previously reported in the literature. Thus, the outcomes of this approach are relatively unknown, and this approach has been previously regarded as extremely risky. METHODS: Thirty-one patients at our institution underwent combined cardiac surgery and liver transplant. Patients with at least one-year follow-up were included. The Leave-One-Out Cross-Validation (LOOCV) machine-learning approach was used to generate a model for mortality. RESULTS: Median follow-up was 8.2 years (IQR 4.6-13.6 y). One- and five-year survival was 74.2% (N=23) and 55% (N=17), respectively. Negative predictive factors of survival included recipient age>60 years (P=0.036), NASH-cirrhosis (P=0.031), Coronary Artery Bypass-Graft (CABG)-based CS (P=0.046) and pre-operative renal dysfunction (P=0.024). The final model demonstrated that renal dysfunction had a relative weighted impact of 3.2 versus CABG (1.7), age ≥60y (1.7) or NASH (1.3). Elevated LT+CS risk score was associated with an increased five-year mortality after surgery (AUC=0.731, P=<0.001). Conversely, the widely accepted STS-PROM calculator was unable to successfully stratify patients according to 1- (P>0.99) or 5-year (P=0.695) survival rates. CONCLUSIONS: This is the largest series describing combined LT+CS, with joint surgical management appearing feasible in highly selected patients. CABG and pre-operative renal dysfunction are important negative predictors of mortality. The four-variable LT+CS score may help predict patients at high risk for post-operative mortality.

Biliary complications following split liver transplantation in adult recipients: a matched pair analysis on single-center experience.

The utilization of split liver grafts can increase access to liver transplantation (LT) for adult patients, particularly when liver grafts are shared between 2 adult recipients. However, it is yet to be determined whether split liver transplantation (SLT) increases the risk of biliary complications (BCs) compared with whole liver transplantation (WLT) in adult recipients. This retrospective study enrolled 1441 adult patients who underwent deceased donor LT at a single-site between January 2004 and June 2018. Of those, 73 patients underwent SLTs. Graft type for SLT includes 27 right trisegment grafts, 16 left lobes, and 30 right lobes. A propensity score matching analysis selected 97 WLTs and 60 SLTs. Biliary leakage was more frequently seen in SLTs (13.3% vs. 0%; p <0.001), whereas the frequency of biliary anastomotic stricture was comparable between SLTs and WLTs (11.7% vs. 9.3%; p=0.63). Graft and patient survival rates of patients undergoing SLTs were comparable to those undergoing WLTs (p=0.42 and 0.57, respectively). In the analysis of the entire SLT cohort, BCs were seen in 15 patients (20.5%) including biliary leakage in 11 patients (15.1%) and biliary anastomotic stricture in 8 patients (11.0%) [both in 4 patients (5.5%)]. The survival rates of recipients who developed BCs were significantly inferior to those without BCs (p <0.01). By multivariate analysis, the split grafts without common bile duct increased the risk of BCs. In conclusion, SLT increases the risk of biliary leakage compared with WLT. Biliary leakage can still lead to fatal infection and thus should be managed appropriately in SLT.

Living Donor Liver Transplantation With Augmented Venous Outflow and Splenectomy: A Promised Land for Small Left Lobe Grafts.

OBJECTIVE: Living donor liver transplantation (LDLT) using small grafts, especially left lobe grafts (H1234-MHV) (LLG), continues to be a challenge due to small-for-size syndrome (SFSS). We herein demonstrate that with surgical modifications, outcomes with small grafts can be improved. METHODS: Between 2012 and 2020, we performed 130 adult LDLT using 61 (47%) LLG (H1234-MHV) in a single Enterprise. The median graft-to-recipient weight ratio was 0.84%, with graft-to-recipient weight ratio <0.7% accounting for 22%. Splenectomy was performed in 72 (56%) patients for inflow modulation before (n=50) or after (n=22) graft reperfusion. In LLG-LDLT, venous outflow was achieved using all three recipient hepatic veins. In right lobe graft (H5678) (RLG)-LDLT, the augmented graft right hepatic vein was anastomosed to the recipient's cava with a large cavotomy. Outcome measures include SFSS, early allograft dysfunction (EAD), and survival. RESULTS: Graft survival rates at 1, 3, and 5 years were 94%, 90%, and 83%, respectively, with no differences between LLG (H1234-MHV) and RLG (H5678). Splenectomy significantly reduced portal flow without increasing the complication rate. Despite the aggressive use of small grafts, SFSS and EAD developed in only 1 (0.8%) and 18 (13.8%) patients, respectively. Multivariable logistic regression revealed model for end-stage liver disease score and LLG (H1234-MHV) as independent risk factors for EAD and splenectomy as a protective factor (odds ratio: 0.09; P =0.03). For LLG (H1234-MHV)-LDLT, patients who underwent prereperfusion splenectomy tended to have better 1-year graft survival than those receiving postreperfusion splenectomy. CONCLUSIONS: LLG (H1234-MHV) are feasible in adult LDLT with excellent outcomes comparable to RLG (H5678). Venous outflow augmentation and splenectomy help lower the threshold of using small-for-size grafts without compromising graft survival.

The Prognostic Utility of Intraoperative Allograft Vascular Inflow Measurements in Donation After Circulatory Death Liver Transplantation.

Donation after circulatory death (DCD) liver transplantation improves deceased donor liver use and decreases waitlist burden, albeit at an increased risk of biliary complications and inferior graft survival. Employing liver vascular inflow measurements intraoperatively permits allograft prognostication. However, its use in DCD liver transplantation is hitherto largely unknown and further explored here. DCD liver transplantation patient records at a single center from 2005 to 2018 were retrospectively scrutinized. Intraoperative flow data and relevant donor parameters were analyzed against endpoints of biliary events and graft survival. A total of 138 cases were chosen. The incidence of cumulative biliary complications was 38%, the majority of which were anastomotic strictures and managed successfully by endoscopic means. The ischemic cholangiopathy rate was 6%. At median thresholds of a portal vein (PV) flow rate of <92 mL/minute/100 g and buffer capacity (BC) of >0.04, both variables were independently associated with risk of biliary events (P = 0.01 and 0.04, respectively). Graft survival was 90% at 12 months and 75% at 5 years. Cox regression analysis revealed a PV flow rate of <50 mL/minute/100 g as predictive of poorer graft survival (P = 0.01). Furthermore, 126 of these DCD livers were analyzed against a propensity-matched group of 378 contemporaneous donation after brain death liver allografts (1:3), revealing significantly higher rates (P < 0.001) of both early allograft dysfunction (70% versus 30%) and biliary complications (37% versus 20%) in the former group. Although flow data were comparable between both sets, PV flow and BC were predictive of biliary events only in the DCD cohort. Intraoperative inflow measurements therefore provide valuable prognostication on biliary/graft outcomes in DCD liver transplantation, can help inform graft surveillance, and its routine use is recommended.

The role of T-tubes and abdominal drains on short-term outcomes in liver transplantation - A systematic review of the literature and expert panel recommendations.

BACKGROUND: This systematic review and expert panel recommendation aims to answer the question regarding the routine use of T-tubes or abdominal drains to better manage complications and thereby improve outcomes after liver transplantation. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel to assess the potential risks and benefits of T-tubes and intra-abdominal drainage in liver transplantation (CRD42021243036). RESULTS: Of the 2996 screened records, 33 studies were included in the systematic review, of which 29 (six RCTs) assessed the use of T-tubes and four regarding surgical drains. Although some studies reported less strictures when using a T-tube, there was a trend toward more biliary complications with T-tubes, mainly related to biliary leakage. Due to the small number of studies, there was a paucity of evidence on the effect of abdominal drains with no clear benefit for or against the use of drainage. However, one study investigating the open vs. closed circuit drains found a significantly higher incidence of intra-abdominal infections when open-circuit drains were used. CONCLUSIONS: Due to the potential risk of biliary leakage and infections, the routine intraoperative insertion of T-tubes is not recommended (Level of Evidence moderate - very low; grade of recommendation strong). However, a T-tube can be considered in cases at risk for biliary stenosis. Due to the scant evidence on abdominal drainage, no change in clinical practice in individual centers is recommended. (Level of Evidence very low; weak recommendation).

Two pumps or one pump? A comparison of human liver normothermic machine perfusion devices for transplantation.

BACKGROUND: Normothermic machine perfusion provides continuous perfusion to ex situ hepatic grafts through the portal vein and the hepatic artery. Because the portal vein has high flow with low pressure and the hepatic artery has low flow with high pressure, different types of perfusion machines have been employed to match the two vessels' infusion hemodynamics. METHODS: We compared transplanted human livers perfused through a 2-pump (n = 9) versus a 1-pump perfusion system (n = 6) where a C-clamp is used as a tubing constrictor to regulate hemodynamics. RESULTS: There was no significant difference between groups in portal vein or hepatic artery flow rate. The 1-pump group had more hemoglobin in the perfusate. However, there was no significant difference in plasma hemoglobin between the 2-pump and 1-pump groups at each time point or in the change in levels, proving no hemolysis occurred due to C-clamp tube constriction. After transplantation, the 2-pump group had two cases of early allograft dysfunction (EAD), whereas the 1-pump group had no EAD. There was no graft failure or patient death in either group during follow-up ranging from 20-52 months. CONCLUSIONS: Our data show that the 1-pump design provided the same hemodynamic output as the 2-pump design, with no additional hemolytic risk, but with the benefits of lower costs, easier transport and faster and simpler setting.

Youngest Composite Full-Face Transplant: A Model for Vascularized Composite Allograft in Younger Populations.

BACKGROUND: The field of face transplantation continues to evolve, with more complex defects being addressed, and, at the same time, increased outcome expectations. Given our unique long-term experience in this field, we consented one of the youngest patients to undergo a full-face transplant. METHODS: An 18-year-old woman presented with complete destruction of her central face and craniofacial structures. She had coexisting major injuries, including pituitary gland, visual axis, and motor control. After extensive rehabilitation and reconstruction techniques, the patient underwent face transplant on May 4, 2017, at the age of 21 years. RESULTS: The total operative time for the recipient was 26 hours. There were no major perioperative complications. Since transplant, the patient has undergone 3 revision surgeries. She is near completely independent from a daily life activity standpoint. She has had 1 episode of rejection above grade II that was successfully treated with a short-term increased in immunosuppression. CONCLUSIONS: Contrary to data in solid organ transplantation where youth is associated with increased risk of rejection, our current algorithm in immunosuppression, combined with this patient's compliance, has led to only 1 rejection episode beyond grade II. This successful transplant can serve as a model for future vascularized composite transplants in younger populations.

Long term outcomes and complications of reno-portal anastomosis in liver transplantation: results from a propensity score-based outcome analysis.

Diffuse splanchnic vein thrombosis (DSVT) remains a serious challenge in liver transplantation (LT). Reno-portal anastomosis (RPA) has previously been reported as a valid option for management of patients with DSVT during LT. The aim of this study was to evaluate post-transplant renal function and surgical outcomes of patients with DSVT who underwent RPA during LT. Between January 2005 and December 2017, 1270 patients underwent LT at our institution, including 16 with DSVT managed with RPA (RPA group). We compared renal function and surgical outcomes in these patients to outcomes in 48 propensity score (PS)-matched patients without thrombosis (control group), using a 1:3 matching model. The two groups had similar rates of postoperative portal vein thrombosis (PVT), renal dysfunction as measured by estimated glomerular filtration rate (eGFR), and overall postoperative complications (Clavien grade III), although the RPA group had a higher incidence of postoperative upper gastrointestinal (GI) bleeding (31.3% vs 4.2%; P = 0.009) that had no clinical consequence. There were no significant differences in five-year graft and patient survival rates between the groups (P = 0.133 and P = 0.166, respectively). RPA is an established technique in the management of patients with DSVT during LT, with comparable outcomes to patients without thrombosis. Our report is the first to demonstrate similar surgical outcomes, including long-term renal function, in LT recipients with or without RPA.

Conditional probability of graft survival in liver transplantation using donation after circulatory death grafts - a retrospective study.

The use of livers from donation after circulatory death (DCD) is historically characterized by increased rates of biliary complications and inferior short-term graft survival (GS) compared to donation after brain death (DBD) allografts. This study aimed to evaluate the dynamic prognostic impact of DCD livers to reveal whether they remain an adverse factor even after patients survive a certain period following liver transplant (LT). This study used 74 961 LT patients including 4065 DCD LT in the scientific registry of transplant recipients from 2002-2017. The actual, 1 and 3-year conditional hazard ratio (HR) of 1-year GS in DCD LT were calculated using a conditional version of Cox regression model. The actual 1-, 3-, and 5-year GS of DCD LT recipients were 83.3%, 73.3%, and 66.3%, which were significantly worse than those of DBD (all P < 0.01). Actual, 1-, and 3-year conditional HR of 1-year GS in DCD compared to DBD livers were 1.87, 1.49, and 1.39, respectively. Graft loss analyses showed that those lost to biliary related complications were significantly higher in the DCD group even 3 years after LT. National registry data demonstrate the protracted higher risks inherent to DCD liver grafts in comparison to their DBD counterparts, despite survival through the early period after LT. These findings underscore the importance of judicious DCD graft selection at individual center level to minimize the risk of long-term biliary complications.

Successful Treatment of Life-Threatening COVID-19 Infection in a Face Transplant Recipient.

ABSTRACT: Recent literature suggests that severe COVID-19 is associated with an exaggerated immune response during viral infection, resulting in cytokine storm. Although elevated plasma interleukin 6 (IL-6) has been reported in severe COVID-19 infections, and treatment with anti-IL-6 (tocilizumab) has demonstrated promising outcomes both domestically and abroad, reports remain limited and therapeutic regimens vary considerably. Furthermore, research pertaining to transplant recipients, COVID-19 infection, and anti-IL-6 therapy remains underdeveloped. Herein, we report the successful treatment of the only reported facial vascularized composite allograft (VCA) recipient who contracted severe COVID-19 and the first reported VCA recipient with COVID-19 infection that received anti-IL-6 immunotherapy resulting in an excellent recovery despite his multiple preexisting and COVID-19-related comorbidities-adult respiratory distress syndrome, acute renal failure requiring hemodialysis, and concomitant sepsis due to extensive drug-resistant bacterial pneumonia upon presentation. To date, he has not demonstrated any anti-IL-6 drug-related adverse effects. This preliminary report also suggests that our immunosuppressed VCA patients can indeed demonstrate a robust cytokine response during COVID-19 infection and may also respond favorably to emerging anticytokine immune therapies. We hope that our experience proves helpful to other centers that might encounter critically ill VCA recipients in the ongoing COVID-19 pandemic and in the years to follow.

Ex Situ Liver Machine Perfusion: The Impact of Fresh Frozen Plasma.

The primary aim of this single-center, phase 1 exploratory study was to investigate the safety, feasibility, and impact on intrahepatic hemodynamics of a fresh frozen plasma (FFP)-based perfusate in ex situ liver normothermic machine perfusion (NMP) preservation. Using an institutionally developed perfusion device, 21 livers (13 donations after brain death and 8 donations after circulatory death) were perfused for 3 hours 21 minutes to 7 hours 52 minutes and successfully transplanted. Outcomes were compared in a 1:4 ratio to historical control patients matched according to donor and recipient characteristics and preservation time. Perfused livers presented a very low resistance state with high flow during ex situ perfusion (arterial and portal flows 340 ± 150 and 890 ± 70 mL/minute/kg liver, respectively). This hemodynamic state was maintained even after reperfusion as demonstrated by higher arterial flow observed in the NMP group compared with control patients (220 ± 120 versus 160 ± 80 mL/minute/kg liver, P = 0.03). The early allograft dysfunction (EAD) rate, peak alanine aminotransferase (ALT), and peak aspartate aminotransferase (AST) levels within 7 days after transplantation were lower in the NMP group compared with the control patients (EAD 19% versus 46%, P = 0.02; peak ALT 363 ± 318 versus 1021 ± 999 U/L, P = 0.001; peak AST 1357 ± 1492 versus 2615 ± 2541 U/L, P = 0.001 of the NMP and control groups, respectively). No patient developed ischemic type biliary stricture. One patient died, and all other patients are alive and well at a follow-up of 12-35 months. No device-related adverse events were recorded. In conclusion, with this study, we showed that ex situ NMP of human livers can be performed safely and effectively using a noncommercial device and an FFP-based preservation solution. Future studies should further investigate the impact of an FFP-based perfusion solution on liver hemodynamics during ex situ normothermic machine preservation.

First birth from a deceased donor uterus in the United States: from severe graft rejection to successful cesarean delivery.

Uterus transplantation is the only known potential treatment for absolute uterine factor infertility. It offers a unique setting for the investigation of immunologic adaptations of pregnancy in the context of the pharmacologic-induced tolerance of solid organ transplants, thus providing valuable insights into the early maternal-fetal interface. Until recently, all live births resulting from uterus transplantation involved living donors, with only 1 prior birth from a deceased donor. The Cleveland Clinic clinical trial of uterus transplantation opened in 2015. In 2017, a 35 year old woman with congenital absence of the uterus was matched to a 24 year old parous deceased brain-dead donor. Transplantation of the uterus was performed with vaginal anastomosis and vascular anastomoses bilaterally from internal iliac vessels of the donor to the external iliac vessels of the recipient. Induction and maintenance immunosuppression were achieved and subsequently modified in anticipation of pregnancy 6 months after transplant. Prior to planned embryo transfer, ectocervical biopsy revealed ulceration and a significant diffuse, plasma cell-rich mixed inflammatory cell infiltrate, with histology interpreted as grade 3 rejection suspicious for an antibody-mediated component. Aggressive immunosuppressive regimen targeting both cellular and humoral rejection was initiated. After 3 months of treatment, there was no histologic evidence of rejection, and after 3 months from complete clearance of rejection, an uneventful embryo transfer was performed and a pregnancy was established. At 21 weeks, central placenta previa with accreta was diagnosed. A healthy neonate was delivered by cesarean hysterectomy at 34 weeks' gestation. In summary, this paper highlights the first live birth in North America resulting from a deceased donor uterus transplant. This achievement underscores the capacity of the transplanted uterus to recover from a severe, prolonged rejection and yet produce a viable neonate. This is the first delivery from our ongoing clinical trial in uterus transplantation, including the first reported incidence of severe mixed cellular/humoral rejection as well as the first reported placenta accreta.

Does graft hemodynamics affect the risk of hepatocellular carcinoma recurrence after liver transplantation?

Although experimental studies have reported that hepatic ischemia-reperfusion injury promotes tumor growth and metastases, the impact of graft hemodynamics on the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is unclear. To investigate the association between graft hemodynamics and HCC recurrence after LT, we conducted a retrospective analysis of 279 patients who underwent LT for HCC. Graft hemodynamics including portal vein flow (PVF), hepatic artery flow (HAF), and total hepatic flow (THF) was analyzed as a predictor of HCC recurrence, using competing risk regression analyses. The cutoff values of PVF, HAF, and THF were set at the lower quartile of distribution. A cumulative recurrence curve demonstrated that low THF (<1511 mL/min, P = .005) was significantly associated with increased recurrence, whereas neither low PVF (<1230 mL/min, P = .150) nor low HAF (<164 mL/min, P = .110) was significant. On multivariate analysis, outside Milan criteria (sub-hazard ratio [SHR] = 3.742; P < .001), microvascular invasion (SHR = 3.698; P < .001), and low THF (SHR = 2.359; P = .010) were independently associated with increased HCC recurrence. In conclusion, our findings suggest that graft hemodynamics may play an important role in HCC recurrence after LT.

Coronavirus disease 2019 in an orthotopic liver transplant recipient living with human immunodeficiency virus.

Coronavirus disease 2019 (COVID-19), mediated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can manifest with flu-like illness and severe pneumonia with acute respiratory distress syndrome (ARDS). Immunocompromised patients merit particular attention as altered host immunity may influence both disease severity and duration of viral shedding as is described with several other ribonucleic acid respiratory viruses. Yet immunocompromised status alone, in the absence of other comorbidities, may not necessarily predict severe illness presentations and poorer clinical outcomes as indicated by recent reports of COVID-19-infected solid organ transplant recipients and people living with human immunodeficiency virus (HIV). Such patients may even be spared the robust inflammatory response that precipitates ARDS associated with COVID-19, complicating the management of iatrogenic immunosuppression in this setting. We present a case of an orthotopic liver transplant recipient with well-controlled HIV who successfully recovered from a mild, flu-like illness attributed to SARS-CoV-2.

Improved Survival Following Living Donor Liver Transplantation for Pediatric Acute Liver Failure: Analysis of 20 Years of US National Registry Data.

This study estimated the utility of technical variant grafts (TVGs), such as split/reduced liver transplantation (SRLT) and living donor liver transplantation (LDLT), in pediatric acute liver failure (PALF). PALF is a devastating condition portending a poor prognosis without liver transplantation (LT). Pediatric candidates have fewer suitable deceased donor liver transplantation (DDLT) donor organs, and the efficacy of TVG in this setting remains incompletely investigated. PALF patients from 1995 to 2015 (age <18 years) were identified using the Scientific Registry of Transplant Recipients (n = 2419). Cox proportional hazards model and Kaplan-Meier curves were used to assess outcomes. Although wait-list mortality decreased (19.1% to 9.7%) and successful transplantations increased (53.7% to 62.2%), patients <1 year of age had persistently higher wait-list mortality rates (>20%) compared with other age groups (P < 0.001). TVGs accounted for only 25.7% of LT for PALF. In the adjusted model for wait-list mortality, among other factors, increased age (subhazard ratio [SHR], 0.97 per year; P = 0.020) and access to TVG were associated with decreased risk (SHR, 0.37; P < 0.0001). LDLT recipients had shorter median waiting times compared with DDLT (LDLT versus DDLT versus SRLT, 3 versus 4 versus 5 days, respectively; P = 0.017). In the adjusted model for post-LT survival, LDLT was superior to DDLT using whole grafts (SHR, 0.41; P = 0.004). However, patient survival after SRLT was not statistically different from DDLT (SHR, 0.75; P = 0.165). In conclusion, despite clear advantages to reduce wait-list mortality, TVGs have been underutilized in PALF. Early access to TVG, especially from LDLT, should be sought to further improve outcomes.