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Background Given the success of direct-acting antivirals (DAAs) in treating hepatitis C (HCV), interest is growing in utilizing solid organs from allografts with active HCV to expand donor availability. Aim To review post-transplant outcomes and patient survival in HCV-negative recipients receiving solid organ transplants (SOT) from viraemic, that is, HCV+/NAT+ (nucleic acid testing) allografts. Methods A literature search was conducted on PubMed and EMBASE from 01/01/2007 to 4/17/2021 for articles matching eligibility criteria. Two authors independently screened titles and abstracts. Disagreements were solved by a third independent reviewer. Methodological quality assessment was done using a modified Newcastle-Ottawa scale (NOS). Data synthesis was done qualitatively using median, ranges and percentages. Results Thirty-five studies were included (or 852 SOTs): 343 kidney, 233 heart, 204 liver, and 72 lung transplants from viraemic allografts. Of the recipients eligible for sustained virological response at 12 weeks (SVR12) calculation, 100% achieved cure from HCV. No deaths/graft failures were reported to be related to HCV transmission. Seven SOT recipients had viral relapse, with all seven patients treated successfully. Four patients developed fibrosing cholestatic hepatitis with complete resolution post-treatment. Conclusions Transplanting viraemic organs into uninfected individuals can become the standard of care for patients who do not have contraindications to DAAs.

Objectives There is an 18.9% discard rate among kidney allografts. Here, we aimed to determine predictors of kidney discard and construct an index to identify high-probability discard kidney allografts prior to procurement. Materials and methods A total of 102 246 potential kidney allograft donors from the Organ Procurement and Transplantation Network database were used in this analysis. The cohort was randomized into 2 groups. The training set included 67% of the cohort and was used to derive a predictive index for discard that comprised 21 factors identified by univariate and multivariate logistic regression analysis. The validation set included 33% and was used to internally validate the kidney discard risk index. Results In 77.3% of donors, at least 1 kidney was used for transplant, whereas in 22.7% of donors, both kidneys were discarded. The kidney discard risk index was highly predictive of discard with a C statistic of 0.89 (0.88-0.89). The bottom 10th percentile had a discard rate of 0.73%, whereas the top 10th percentile had a discard rate of 83.65%. The 3 most predictive factors for discard were age, creatinine level, and hepatitis C antibody status. Conclusions We identified 21 factors predictive of discard prior to donor procurement and used these to develop a kidney discard risk index with a C statistic of 0.89.

Background Independent studies provide evidence that low volume pediatric solid organ transplant centers have inferior outcomes compared to high volume pediatric centers. The study assessed whether patients treated at low volume pediatric centers have access to higher volume pediatric centers, which offer potentially better outcomes. Methods We analyzed center specific data on 467 pediatric solid organ transplant centers in the U.S using the Organ Procurement and Transplantation Network database from 2002 to 2014. The proximities of low volume pediatric centers to high volume pediatric centers were determined using Maptive, a tool based on Google Maps. Results Most low volume pediatric transplant centers focused on transplantation of adults (84% heart, 83% liver, and 93% kidney programs). A majority of low volume pediatric centers (77% for heart, 53% for lung, 68% for liver and 90% for kidney) were within 150 miles of high volume centers. Among all children listed for transplantation, 30.7% were listed in low volume pediatric centers. Most low volume pediatric centers are adult focused and near high volume pediatric centers. Conclusion We need greater scrutiny of outcomes, particularly waitlist outcomes, of low volume pediatric solid organ transplant centers located close to high volume pediatric solid organ transplant centers. Type of Study and Level of Evidence Retrospective Comparative Study, Level III.

The field of liver transplantation has shifted considerably in the MELD era, including changing allocation, immunosuppression, and liver failure etiologies, as well as better supportive therapies. Our aim was to evaluate the predictive accuracy of the MELD score over time. The United Network for Organ Sharing provided de-identified data on 120 156 patients listed for liver transplant from 2002-2016. The ability of the MELD score to predict 90-day mortality was evaluated by a concordance (C-) statistic and corroborated with competing risk analysis. The MELD score's concordance with 90-day mortality has downtrended from 0.80 in 2003 to 0.70 in 2015. While lab MELD scores at listing and transplant climbed in that interval, score at waitlist death remained steady near 35. Listing age increased from 50 to 54 years. HCV-positive status at listing dropped from 33 to 17%. The concordance of MELD and mortality does not differ with age (>60 = 0.73

Background The aim of this study was to assess improvements in long-term survival of pediatric patients after liver transplantation by analyzing outcomes in transplant recipients who survived beyond 1 year after transplantation. There has been a marked increase in the 1-year survival of pediatric patients, from 78% in transplant recipients between 1987 and 1990 to 95% in transplant recipients between 2011 and 2017. The long-term outcomes have not seen a similar trend, creating a disparity that warrants analysis. Methods We analyzed 13 753 pediatric patients who survived for 1 year after receiving orthotopic liver transplantation between 1987 and 2017. The study period was divided into six eras. Outcomes were analyzed using the Kaplan-Meier method for time-to-event analysis, and multivariable Cox regression. Results There were no significant gains in long-term outcomes among 1-year survivors over the past three decades. Log-rank tests for equality of survivor functions between each era and 1987-1990 were not statistically significant. Cause of death analysis revealed that although infections caused 20.6% of deaths in patients transplanted between 1987 and 1990, this number dropped to 5.6% in those transplanted between 2011 and 2017 (p = .01). Malignancy caused 10.6% of deaths in 1987-1990 but caused 22.2% of the deaths in 2011-2017 (p = .04). Conclusion Despite the gratifying gains in short-term survival of pediatric patients, 1-year survivors have no significant improvements in long-term survival after undergoing a liver transplantation. Long-term sequelae of immunosuppression, such as malignancy and infection, continue to be the most common causes of death. This study highlights the necessity for better long-term management of immunosuppression.

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.

Introduction: The disparity between the number of individuals on the wait list and available liver allografts creates the need for a system that maximizes donor liver utilization and predicts graft failure. Research Question: This study aimed to determine the relationship between donor Gamma-Glutamyl Transferase (GGT), liver discard, and graft failure. Design: Through multivariate analysis from 53 966 deceased liver donors, we adjusted for donor clinical and demographic characteristics and compared donor GGT with allograft discard. We compared donor GGT ranges with graft failure and analyzed data from 47 269 liver recipients. Results: After adjusting for other factors, donor GGT was significantly associated with liver discard, with GGT over 200 U/L being most significant (OR 2.74, CI 2.51-2.99). Donor GGT under 20 U/L was also found to be a protective factor for post-transplant graft failure (HR 0.91, CI 0.83 – 1.00). Conclusion: Going forward, GGT should be included among other characteristics associated with allograft discard considered during the procurement process.

Background Successful liver transplantation is dependent on restoration of hepatic arterial (HA) flow. Although uncommon, some native recipient HAs are not suitable or inadequate for anastomosis, thereby necessitating extra-anatomic HA reconstruction. Splenic artery transposition (SAT) is 1 method of HA reconstruction, in which the recipient splenic artery is transposed to reestablish perfusion of the donor liver. Due to the rarity of the technique, literature describing outcomes is limited. In the current report, we describe 3 patients (2 adults, 1 pediatric) who underwent complex upper abdominal surgery before whole-organ deceased donor liver transplantation with SAT. Methods The demographic and patient care information was collected prospectively and subsequently reviewed retrospectively. Given the de-identified nature of the data included, this study was exempt from approval from an ethics board. Results Recipient splenic arteries were dissected from their origin at the celiac trunk, for approximately 3-5 cm to ensure a gentle anterior-cranial curve toward the right upper quadrant, allowing anastomosis to the donor celiac trunk in an end-to-end fashion. Postoperatively, all 3 patients had rapid normalization of liver function tests and brisk HA flow demonstrated by Doppler ultrasound. Longer-term follow-up, ranging from 1 to 3 years, reveals continued patency of the reconstructed HAs and liver function tests within normal limits. Conclusions Our experience points to SAT as a safe and effective technique for extra-anatomic HA reconstruction.

Of the 600 pediatric candidates added to the liver waiting list annually, 100 will remain waiting while over 100 liver allografts are discarded, often for subjective reasons.We created a risk index to predict discard to better optimize donor supply. We used the UNOS database to retrospectively analyze 17 367 deceased donors (≤18 years old) through univariate and multivariate logistic regression models. Deceased donor clinical characteristics and laboratory values were independent variables with discard being the dependent variable in the analysis. Significant univariate factors (P-value .05) comprised the multivariate analysis. Significant variables from the multivariate analysis were incorporated into the pDSRI, producing a risk score for discard.From 17 potential factors, 11 were identified as significant predictors (P .05) of pediatric liver allograft discard. The most significant risk factors were as follows: DCD; total bilirubin10 mg/dL, and alanine transaminase (ALT) ≥500 IU/L. The pDSRI has a C-statistic of 0.846 for the training set and 0.840 for the validation set.The pDSRI uses 11 significant risk factors, including elevated liver function tests, donor demographics, and donor risk/type to accurately predict risk of pediatric liver allograft discard and serve as a tool that may maximize donor yield.

Background The clinical course of COVID‐19 in pediatric solid organ transplant recipients remains ambiguous. Though preliminary experiences with adult transplant recipients have been published, literature centered on the pediatric population is limited. We herein report a multi‐center, multi‐organ cohort analysis of COVID‐19 positive transplant recipients ≤ 18 years at time of transplant. Methods Data were collected via institutions’ respective electronic medical record systems. Local review boards approved this cross‐institutional study. Results Among 5 transplant centers, 26 patients (62% male) were reviewed with a median age of 8 years. 6 were heart recipients, 8 kidney, 10 liver, and 2 lung. Presenting symptoms included cough (n=12 (46%)), fever (n=9 (35%)), dry/sore throat (n=3 (12%)), rhinorrhea (n=3 (12%)), anosmia (n=2 (8%)), chest pain (n=2 (8%)), diarrhea (n=2 (8%)), dyspnea (n=1 (4%)), and headache (n=1 (4%)). Six patients (23%) were asymptomatic. No patient required supplemental oxygen, intubation, or ECMO. Eight patients (31%) were hospitalized at time of diagnosis, 3 of whom were already admitted for unrelated problems. Post‐transplant immunosuppression was reduced for only 2 patients (8%). All symptomatic patients recovered within 7 days. Conclusions Our multi‐institutional experience suggests the prognoses of pediatric transplant recipients infected with COVID‐19 may mirror those of immunocompetent children, with infrequent hospitalization and minimal treatment, if any, required.

Background We describe the successful pediatric liver transplant for unresectable hepatoblastoma in a 4‐year‐old male with COVID‐19 prior to transplant. The first negative nasopharyngeal (NP) swab was documented one month after initial diagnosis, when SARS‐CoV‐2 antibodies were also detected. The patient was actively listed for liver transplant after completing four blocks of a SIOPEL‐4 based regimen due to his PRETEXT IV disease which remained unresectable. Following three additional negative NP swabs and resolution of symptoms for four weeks, he underwent a whole‐organ pediatric liver transplant. Methods COVID‐19 positivity determined via NP swab SARS‐CoV‐2 real‐time RT‐PCR (Hologic Aptima SARS‐CoV‐2 RT‐PCR assay). IgG and IgM total SARS‐ CoV‐2 antibodies detected by Ortho Clinical Diagnostics VITROS® Immunodiagnostics Products Anti‐SARS‐CoV‐2 Test. Results Patient received standard prednisone and tacrolimus‐based immunosuppression without induction therapy following transplant. Post‐transplant course was remarkable for neutropenia and thrombocytopenia, with discharge home on post‐transplant day #11. Surveillance tests have remained negative with persistent SARS‐CoV‐2 IgG antibodies at six weeks after transplant. Conclusions We describe one of the earliest, if not the first case of liver transplant following recent recovery from COVID‐19 in a pediatric patient with a lethal malignant liver tumor. A better understanding of how to balance the risk profile of transplant in the setting of COVID‐19 with disease progression if transplant is not performed is needed. We followed existing ASTS guidelines to document clearance of the viral infection and resolution of symptoms before transplant. This case highlights that pediatric liver transplantation can be safely performed upon clearance of COVID‐19.

Background PELD scores are used to reduce waitlist mortality, but they do not accurately predict likelihood of prolonged length-of-stay or higher costs associated with it. This study aims to create a pediatric length-of-stay (LOS) index to predict increased risk of prolonged stay following liver transplantation. Methods The scoring system generated predicts length-of-stay following pediatric liver transplantation. With univariate and multivariate analyses on data from 5669 pediatric liver transplant recipients, independent recipient/donor risk factors for prolonged stay (>30 days) were identified. Multiple imputations accounted for missing variables. Results The most significant factors were ICU admission (OR 2.92, CI 2.27-3.75), recipient bilirubin >32 (OR 2.35, CI 1.70-3.25), and hemodialysis 1 week before transplantation (OR 2.27, CI 1.57-3.27). The LOS index assigns weighted scoring points to factors to predict prolonged stay (C-statistic of .72). The index demonstrated discrimination across the population after dividing it into quartiles for prolonged stay. Conclusions The pediatric LOS index, utilizing 13 donor/recipient factors, can assess the risk for pediatric liver transplantation prolonged stay. Important predictive factors are hemodialysis, ICU admission, recipient weight and bilirubin, and recipient life support status.

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 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.

Reports on the long-term outcomes and immunosuppressive regimens of multiorgan transplant patients are limited. Here, we describe a patient with cystic fibrosis complicated by multiorgan failure who was successfully treated with combined liver lung transplant and delayed kidney transplant, resulting in excellent outcomes. Delayed kidney transplant was done to reduce the operative stress of a single procedure, giving time for adequate resuscitation and weaning from vasopressors. Our patient's postoperative course was complicated by post-transplant lymphoproliferative disease, which was successfully treated with rituximab and reduced dosages of immunosuppression.

Given the critical shortage of donor livers, marginal liver allografts have potential to increase donor supply. We investigate trends and long-term outcomes of liver transplant using national share allografts transplanted after rejection at the local and regional levels. We studied a cohort of 75 050 candidates listed in the Organ Procurement and Transplantation Network for liver transplantation between 2002 and 2016. We compared patients receiving national share and regional/local share allografts from 2002-2006, 2007-2011, and 2012-2016, performing multivariate Cox regression for graft survival. Recipient and center-level covariates that were not significant (P .05) were removed. Graft survival of national share allografts improved over time. National share allografts had a 26% increased risk for graft failure in 2002-2006 but no impact on graft survival in 2007-2011 and 2012-2016. The cold ischemia time (CIT) of national share allografts decreased from 10.4 to 8.0 hours. We demonstrate that CIT had significant impact on graft survival using national share allografts (CIT6 hours: hazard ratio 0.75 and CIT12 hours: hazard ratio 1.25). Despite a trend toward sicker recipients and poorer quality allografts, graft survival outcomes using national share allografts have improved to benchmark levels. Reduction in cold ischemia time is a possible explanation.

Kidney transplantation is the treatment of choice in pediatric patients with end-stage renal disease. This population presents technical challenges particularly in those less than 20 kg due to anomalous anatomy, vascular access issues prior to transplantation, and a generally small size for age. Standard allograft outflow is usually achieved utilizing the iliac veins or IVC. When use of the iliocaval system is not feasible, alternative anastomosis must be considered. Herein, we report a case of a pediatric kidney transplantation where successful allograft outflow was achieved using the SMV when he was found to have an atretic IVC intraoperatively. In this setting, use of the portal system was required to achieve adequate allograft outflow. We created a donor iliac graft for added length to anastomose the renal vein with the SMV. In the setting of IVC occlusion with poor drainage, we utilized a patent vessel with larger caliber for outflow to reduce the risk of high venous pressures, allograft failure, venous rotation, and thrombosis. We conclude that the SMV may serve as an alternative outflow tract in the small pediatric patient and provides the vessel caliber needed to reduce the risks of complications.

The initial experience with ABO incompatible (ABOi) orthotopic liver transplantations (OLTs) was dismal. In the current study, we investigated whether ABOi pediatric OLTs could achieve acceptable patient outcomes. The option for ABOi transplantation is vital because critically ill children have limited access to donor liver allografts.Kaplan-Meier and multivariate Cox analysis was performed on data collected from 13,179 pediatric OLT recipients in the United Network for Organ Sharing database, including 540 ABOi recipients. We also analyzed 18 pediatric recipients of ABOi OLTs at Texas Children's Hospital. Recipients were divided into 2 groups: transplanted between 1987 to 2002 (remote era) and 2002 to 2013 (modern era).Analysis revealed 4 main points. First, there was a significant (p0.01) improvement in ABOi OLT survival in the modern era. Second, threshold analysis revealed superior outcomes (p0.01) for OLT recipients younger than 2 years of age. Third, survival outcomes for ABOi and ABO-identical OLTs were the same for recipients younger than 2 years: ABOi was 91.8% (1 year) and 88.4% (5 year), and ABO identical was 91.5% (1 year) and 86.7% (5 year) (p = 0.94). Lastly, we found identical OLT results when analyzing our own institutional experience. To date, there has been a 92.9% survival rate in the modern era compared with 75% in the remote era. All recipients younger than 2 years (n = 9) are still alive, compared with 78% of those older than 2 years.This analysis revealed a significant improvement in the survival of ABOi liver transplant recipients in the modern era. Importantly, ABOi liver transplantation can be performed in recipients younger than 2 years of age with equivalent outcomes compared with ABO-identical recipients.

The purposes of this study were to analyze the effects of an ERS on time to transplantation and to describe our center's experience with OLT for HB. Patients who received OLT for HB between 2000 and 2013 were included. Patient and allograft characteristics, chemotherapy regimens, and prior surgical therapies were examined. The interval between diagnosis and OLT prior to and following the institution of an ERS for transplant was compared. Survival and tumor recurrence were analyzed. Nineteen patients received OLT for HB (mean age 33 months). All children received grafts from deceased donors. Two patients underwent prior resections. Tumor recurred in four patients (21.1%). Both patients who received salvage transplants experienced post-OLT recurrence. Three of the four recurrences occurred in spite of adjuvant chemotherapy. There were three deaths: two from metastatic disease. One- and five-yr survivals were 86.1% and 73.8%. After the institution of the ERS, the mean interval between tissue diagnosis and OLT was significantly reduced. Our series of 19 patients demonstrates a 21% recurrence of HB following OLT despite chemotherapy. Five-yr survival reached 73.8%. A system of early referral can effectively reduce times between diagnosis and transplant.

Highlights • Choledochal cysts are congenital biliary tract dilations that may have vague symptoms, making them difficult diagnoses to make. • Cyst resection is the standard of care due to the increased risk of cholangiocarcinoma. • Efficient diagnosis and referral to an experienced hepatobiliary center is crucial., Introduction Choledochal cysts are rare congenital dilations of the biliary tree that can present with non-specific symptoms such as abdominal pain, jaundice, cholelithiasis and pancreatitis. Although most commonly identified in children, they can be found in the adult population. However, because of the non-specific symptoms, this diagnosis may be difficult to make in the adult. A physician therefore must keep this diagnosis within their differential, as it may arise in an unexpected patient population who may present with a convoluted work up. Case presentation In this report, we present the case of a 50-year-old African American woman with recurrent cholelithiasis, cholangitis and eventually obstructive jaundice despite undergoing a laparoscopic cholecystectomy six years prior. Her only work up at that point was a right upper quadrant ultrasound revealing gallbladder sludge, which led to her cholecystectomy. It was the persistence of her symptoms—abdominal pain, cholangitis and obstructive jaundice—previously attributed to chronic cholecystitis and choledocholithiasis that warranted further work up. After multiple physician visits, she was referred to our academic center after an ERCP was performed and she was found to have a dilation of her common bile duct consistent with a choledochal cyst. Furthermore, the ERCP identified multiple bile duct stones within the cyst. This was not identified on her original ultrasound or prior ERCPs. The patient underwent a complete cyst excision with Roux-en-Y hepaticojejunostomy and did well post-operatively. Discussion This report illustrates how choledochal cysts can be an elusive diagnosis, but may present with repeated infections, recurrent biliary stones, and biliary obstruction despite a cholecystectomy. Had she an MRCP prior to her cholecystectomy, she would likely have avoided multiple surgeries, and years of persistent symptoms. Choledochal cysts are associated with an increased risk of biliary malignancy and therefore cyst excision is the standard of care. Conclusion Although rare, physicians need to keep this diagnosis in mind, and be aware of the clinical and imaging findings consistent with a choledochal cyst in order to facilitate appropriate work up, referral and treatment.

The replaced common hepatic artery (RCHA) is an uncommon arterial anomaly that, when present, makes hepatic arterial reconstruction during liver transplantation technically challenging. At our institution, the reconstruction of the recipient RCHA consists of 2 techniques that include either an infrarenal donor iliac artery aortic conduit or a direct donor celiac trunk anastomosis to the proximal RCHA. Our experience demonstrates that the direct anastomosis to the RCHA provides a reliable source of arterial inflow, allows preservation of the recipient arterial anatomy, and minimizes the dissection required to create an infrarenal aortic conduit. Between September 1998 and April 2019, we performed 1782 liver transplants (1230 adults, >18 years; 552 pediatric

Children undergoing liver transplantation are at a significant risk for intraoperative hemorrhage and thrombotic complications, we aim to identify novel risk factors for massive intraoperative blood loss and transfusion in PLT recipients and describe its impact on graft survival and hospital LOS. We reviewed all primary PLTs performed at our institution between September 2007 and September 2016. Data are presented as n (%) or median (interquartile range). EBL was standardized by weight. Massive EBL and MT were defined as greater than the 85th percentile of the cohort. 250 transplantations were performed during the study period. 38 (15%) recipients had massive EBL, and LOS was 31.5 (15-58) days compared to 11 (7-21) days among those without massive EBL (P < 0.001). MT median LOS was 34 (14-59) days compared to 11 (7-21) days among those without MT (P = 0.001). Upon backward stepwise regression, technical variant graft, operative time, and transfusion of FFP, platelet, and/or cryoprecipitate were significant independent risk factors for massive EBL and MT, while admission from home was a protective factor. Recipient weight was a significant independent risk factor for MT alone. Massive EBL and MT were not statistically significant for overall graft survival. MT was, however, a significant risk factor for 30-day graft loss. PLT recipients with massive EBL or MT had significantly longer LOS and increased 30-day graft loss in patients who required MT. We identified longer operative time and technical variant graft were significant independent risk factors for massive EBL and MT, while being admitted from home was a protective factor.

Background The field of transplantation is shifting outcome priorities from 1-year survival to more comprehensive metrics including transplant rate and waitlist mortality. Identifying disenfranchised candidates (high waitlist death risk, low transplantation chance) can be a focus to improve outcomes. Methods Given the waitlist outcomes (continued waiting, death, and transplantation), we aimed to identify factors predicting the likelihood candidates would undergo transplant or death by performing multivariate competing risk analyses of 121 198 candidates in the United Network for Organ Sharing database. We incorporated these probabilities (likelihood of transplantation and waitlist death) into the Transplant Index (TI) to identify disenfranchised candidates (high likelihood of death, low likelihood of transplantation). Results Half of the patients had low incidences of death and transplantation within 90 days (TI-inactive). The remaining were stratified into 10 groups within a predictive index, the TI. Low TI groups (TI 10, 20, 30) had 90-day transplant rates of 50.8%, 41.6%, and 39.8% respectively, and their respective 90-day death rates were 22.8%, 15.1%, and 10.9%. High TI groups (TI 80, 90, >90) had 90-day transplantation rates of 53.7%, 64.3%, and 73.9%, respectively, and 90-day death rates of 5.9%, 6.5%, and 6.7% respectively. As TI increased, the likelihood of transplantation increased and that of death decreased. Low-TI groups represent the disenfranchised candidates. Conclusions The TI identifies disenfranchised candidates on the adult liver transplant waitlist. This is the subgroup that would benefit the most from efforts to increase access to transplantation.

The risk of mineral and bone disorders among patients with chronic kidney disease is substantially elevated, owing largely to alterations in calcium, phosphorus, vitamin D, parathyroid hormone, and fibroblast growth factor 23. The interwoven relationship among these minerals and hormones results in maladaptive responses that are differentially affected by the process of kidney transplantation. Interpretation of conventional labs, imaging, and other fracture risk assessment tools are not standardized in the post-transplant setting. Post-transplant bone disease is not uniformly improved and considerable variation exists in monitoring and treatment practices. A spectrum of abnormalities such as hypophosphatemia, hypercalcemia, hyperparathyroidism, osteomalacia, osteopenia, and osteoporosis are commonly encountered in the post-transplant period. Thus, reducing fracture risk and other bone-related complications requires recognition of these abnormalities along with the risk incurred by concomitant immunosuppression use. As kidney transplant recipients continue to age, the drivers of bone disease vary throughout the post-transplant period among persistent hyperparathyroidism, de novo hyperparathyroidism, and osteoporosis. The use of anti-resorptive therapies require understanding of different options and the clinical scenarios that warrant their use. With limited studies underscoring clinical events such as fractures, expert understanding of MBD physiology, and surrogate marker interpretation is needed to determine ideal and individualized therapy.

An index that predicts liver allograft discard can effectively grade allografts and can be used to preferentially allocate marginal allografts to aggressive centers. The aim of this study is to devise an index to predict liver allograft discard using only risk factors available at the time of initial DonorNet offer.Using univariate and multivariate analyses on a training set of 72 297 deceased donors, we identified independent risk factors for liver allograft discard. Multiple imputation was used to account for missing variables.We identified 15 factors as significant predictors of liver allograft discard; the most significant risk factors were: total bilirubin10 mg/dL (odds ratio [OR], 25.23; confidence interval [CI], 17.32-36.77), donation after circulatory death (OR, 14.13; CI, 13.30-15.01), and total bilirubin 5 to 10 mg/dL (OR, 7.57; 95% CI, 6.32-9.05). The resulting Discard Risk Index (DSRI) accurately predicted the risk of liver discard with a C statistic of 0.80. We internally validated the model with a validation set of 37 243 deceased donors and also achieved a 0.80 C statistic. At a DSRI at the 90th percentile, the discard rate was 50% (OR, 32.34; CI, 28.63-36.53), whereas at a DSRI at 10th percentile, only 3% of livers were discarded.The use of the DSRI can help predict liver allograft discard. The DSRI can be used to effectively grade allografts and preferentially allocate marginal allografts to aggressive centers to maximize the donor yield and expedite allocation.

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 Takotsubo’s 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.

Multidisciplinary hepatocellular carcinoma (HCC) treatment is associated with optimal outcomes. There are few data analyzing the impact of treating hospitals' therapeutic offerings on survival. We performed a retrospective cohort study of patients aged 18-70 years with HCC in the National Cancer Database (2004-2012). Hospitals were categorized based on the level of treatment offered (Type I-nonsurgical; Type II-ablation; Type III-resection; Type IV-transplant). Associations between overall risk of death and hospital type were evaluated with multivariable Cox shared frailty modeling. Among 50,381 patients, 65% received care in Type IV hospitals, 26% in Type III, 3% in Type II, and 6% in Type I. Overall 5-year survival across modalities was highest at Type IV hospitals (untreated: Type IV-13.1% versus Type I-5.7%, Type II-7.0%, Type III-7.4% [log-rank, P < 0.001]; chemotherapy and/or radiation: Type IV-18.1% versus Type I-3.6%, Type II-4.6%, Type III-7.7% [log-rank, P < 0.001]; ablation: Type IV-33.3% versus Type II-13.6%, Type III-23.6% [log-rank, P < 0.001]; resection: Type IV-48.4% versus Type III-39.1% [log-rank, P < 0.001]). Risk of death demonstrated a dose-response relationship with the hospital type-Type I (ref); Type II (hazard ratio [HR] 0.81, 95% confidence interval [0.73-0.90]); Type III (HR 0.67 [0.62-0.72]); Type IV hospitals (HR 0.43 [0.39-0.47]). Conclusion: Although care at hospitals offering the full complement of HCC treatments is associated with decreased risk of death, one third of patients are not treated at these hospitals. These data can inform the value of health policy initiatives regarding regionalization of HCC care.

Objective The aim of this study was to assess improvements in long-term survival after liver transplant by analyzing outcomes in transplant recipients who survived beyond 1 year. Summary of background data Gains in short-term survival following liver transplantation have been gratifying. One-year survival in 1986 was 66% improved to over 92% in 2015. However, little is known about why long-term has not seen similar success. Methods We analyzed 111,568 recipients from 1987 to 2016 using the Kaplan-Meier method for time-to-event analysis and multivariable Cox regression. Results There were no significant gains in unadjusted long-term outcomes among 1-year survivors over the past 30 years. Only the time periods of 1987 to 1990 [hazard ratio (HR) 1.35, confidence interval CI) 1.28-1.42] and 1991 to 1995 (HR 1.17, CI 1.13-1.21) had a minor increase in risk compared with the period 2011 to 2016. Cause of death analysis suggests malignancy after transplantation is a growing problem and preventing recurrent hepatitis C with direct-acting antivirals (DDAs) may only have a limited impact. Furthermore, rejection leading to graft failure and death had a rare occurrence (1.7% of long-term deaths) especially when compared with the sequelae of long-term immunosuppression: malignancy (16.4%), nonrejection graft failure (9.8%), and infection (10.5%) (P Conclusion In stark contrast to short-term survival, there have been no appreciable improvements in long-term survival following liver transplantation among 1-year survivors. Long-term sequelae of immunosuppression, including malignancy and infection, are the most common causes of death. This study highlights the need for better long-term immunosuppression management.

BACKGROUND: Low case volume has been associated with poorer surgical outcomes in a multitude of surgical procedures. We studied the association among low case volume, outcomes, and the likelihood of pediatric liver transplantation. METHODS: We studied a cohort of 6628 candidates listed in the Organ Procurement and Transplantation Network for primary pediatric liver transplantation between 2002 and 2012; 4532 of the candidates went on to transplantation. Candidates were divided into groups according to the average volume of yearly transplants performed in the listing center over 10 years: >15, 10 to 15, 5 to 9, and RESULTS: 38.5% of the candidates were listed in low-volume centers, those in which CONCLUSIONS: 38.5% of pediatric transplant candidates are listed in low-volume transplant centers and have lower likelihood of transplantation and poorer outcomes. If further studies substantiated these findings, we would advocate consolidating pediatric liver transplantation in higher volume centers.

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.

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.

Use of donation after cardiac death (DCD) donors has been proposed as an effective way to expand the availability of hepatic allografts used in orthotopic liver transplantation (OLT); yet, there remains no consensus in the medical literature as to how to choose optimal recipients and donors based on available information.We queried the United Network of Organ Sharing/Organ Procurement and Transplantation Network database for hepatic DCD allografts used in OLT. As of March 31, 2011, 85,148 patients received hepatic allografts from donation-after-brain-death (DBD) donors, and 2351 patients received hepatic allografts from DCD donors. We performed survival analysis using log-rank and Kaplan-Meier tests. We performed univariate and multivariate analyses using the Cox proportional hazards model. All statistics were performed with SPSS 15.0.Patients receiving hepatic DCD allografts had significantly worse survival compared with patients receiving hepatic DBD allografts. Pediatric patients who received a hepatic DCD allograft had similar survival to those who received a hepatic DBD allograft. The optimal recipient-related characteristics were age50 y, International Normalized Ratio2.0, albumin3.5 gm/dL, and cold ischemia time8 h; optimal donor-related characteristics included age50 y and donor warm ischemia time20 min.By identifying certain characteristics, the transplant clinician's decision-making process can be assisted so that similar survival outcomes after OLT can be achieved with the use of hepatic DCD allografts.

Careful management of immunosuppression is paramount to prevent acute rejection in kidney transplantation. We studied a cohort of 139,875 kidney transplant recipients from the Organ Procurement and Transplantation Network (OPTN) database between 2002 and 2013. We confirmed the analysis with a cohort of 35,277 who received thymoglobulin induction with tacrolimus maintenance, and a third cohort of 12,161 recipients who received basiliximab induction with tacrolimus maintenance. We performed multivariate logistic regression analyses on data from all three cohorts and identified independent risk factors for treated acute rejection at 1 year. Recipient age was a robust risk factor for rejection in all three cohorts in a dose response pattern. Young age (18-25 years) was among the strongest risk factors for rejection in all three cohorts; thymoglobulin cohort: OR 1.87 (1.59-2.19); basiliximab cohort: OR 2.41 (1.89-3.05); and inclusive cohort: OR 1.97 (1.83-2.12). The opposite was true for old age (65-69 years); thymoglobulin cohort: OR 0.69 (0.59-0.81); basiliximab cohort: OR 0.77 (0.62-0.96); and inclusive cohort: OR 0.75 (0.70-0.80). This study is unique because it is the largest and most comprehensive multivariate analysis that demonstrates recipient age is a robust risk factor for acute rejection in an inverse dose response pattern.

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 60 years) 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.

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 factors 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. This article is protected by copyright. All rights reserved.

Background RECQL is a DNA helicase involved in DNA mismatch repair. The RECQL polymorphism, 3′ untranslated region (UTR) A159C, was previously associated with overall survival of patients with resectable pancreatic adenocarcinoma treated with neoadjuvant chemoradiation. In the present study, we examined RECQL for somatic mutations and other polymorphisms and compared these findings with the outcome in patients who received adjuvant or neoadjuvant chemoradiation. We hypothesized that RECQL (i) would be mutated in cancer, (ii) would have polymorphisms linked to the 3′UTR A159C and that either or both events would affect function. We also hypothesized that (iii) these changes would be associated with survival in both cohorts of patients. Material and methods We sequenced RECQL ' s 15 exons and surrounding sequences in paired blood and tumour DNA of 39 patients. The 3′UTR A159C genotype was determined in blood DNA samples from 176 patients with resectable pancreatic adenocarcinoma treated with adjuvant (53) or neoadjuvant (123) chemoradiation. Survival was calculated using the Kaplan–Meier method, with log rank comparisons between groups. The relative impact of genotype on time to overall survival was performed using the Cox proportional hazards model. Results Somatic mutations were found in UTRs and intronic regions but not in exonic coding regions of the RECQL gene. Two single nucleotide polymorphisms (SNPs), located in introns 2 and 11, were found to be part of the same haplotype block as the RECQL A159C SNP and showed a similar association with overall survival. No short-term difference in survival between treatment strategies was found. We identified a subgroup of patients responsive to neoadjuvant therapy in which the 159 A allele conferred strikingly improved long-term survival. Discussion The RECQL 3′UTR A159C SNP is not linked with other functional SNPs within RECQL but may function as a site for regulatory molecules. The mechanism of action needs to be clarified further.

The aim of this study was to highlight the unique case of an intrathoracic mesothelial cyst in a 5-year-old child that was treated with a thoracoscopic resection.Mesothelial cysts are benign cysts lined by a single layer of mesothelial cells. These rare lesions can be found on, or adjacent to, serous membranes but are only occasionally located within the thorax. In children, less than 10 intrathoracic cases have been described thus far, most of which are diaphragmatic in origin.An asymptomatic 5-year-old female presented with a left-sided mediastinal mass incidentally discovered on a chest radiograph during a work-up for scoliosis. Magnetic resonance imaging demonstrated a hypodense, nonenhancing lesion measuring 3 x 2.5 x 8 cm in the left paravertebral region. Video-assisted thoracoscopy was employed for diagnosis and excision. The thin-walled cyst was dissected free from the pleura and completely excised thoracoscopically. Histopathology showed a benign, unilocular cyst lined with a cuboidal mesothelium that stained strongly positive for cytokeratin.Mediastinal mesothelial cysts have very rarely been reported in the pediatric population. In the case presented, the benign cyst was easily excised by using a minimally invasive thoracoscopic approach. Given the appropriate indications, we feel that thoracoscopic resection is well suited for such cases.

Sensenbrenner syndrome, or cranioectodermal dysplasia, is a rare heterogeneic autosomal recessive disorder, affecting ~1 of 1 000 000 live births. The syndrome usually manifests within the first year of life and can present with progressive liver and renal involvement. For all Sensenbrenner patients, renal and liver diseases are the main contributors of morbidity and mortality. In this report, we present the case of a 7-year-old boy with congenital liver disease progressing to liver failure secondary to Sensenbrenner syndrome. For this patient, evidence of liver dysfunction was evident from 2 months of age and progressed to frank cirrhosis and severe portal hypertension with multiple episodes of life-threatening variceal bleeding by age 6. This report illustrates the capability of orthotopic liver transplantation as a viable therapy for those pediatric patients suffering from severe liver failure secondary to a congenital ciliopathy, such as Sensenbrenner syndrome. In fact, early emphasis should be placed on the renal and liver involvement associated with Sensenbrenner syndrome with particular consideration for early referral for transplantation in cases with severe disease. Although the condition is rare, clinicians should be aware of it and its association with fatal liver disease to facilitate appropriate evaluation and referral.

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.

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.

Purpose of review Orthotopic liver transplantation in the pediatric population is a technically challenging undertaking, requiring highly specialized surgical techniques unique to this group. This review describes the most current method of transplantation for these patients. Recent findings Pediatric liver transplantation employs multiple modifications of standard transplant technique, including alternative methods of vascular and biliary anastomoses as well as technical variant grafts. We herein describe how these methods are employed in procurement, back-table preparation, hepatectomy, and allograft implantation. Summary This review provides concise direction of surgical technique for pediatric liver transplant recipients.

A prognostic index to predict survival after liver transplantation could address several clinical needs. Here, we devised a scoring system that predicts recipient survival after pediatric liver transplantation. We used univariate and multivariate analysis on 4565 pediatric liver transplant recipients data and identified independent recipient and donor risk factors for posttransplant mortality at 3 months. Multiple imputation was used to account for missing variables. We identified five factors as significant predictors of recipient mortality after pediatric liver transplantation: two previous transplants (OR 5.88, CI 2.88-12.01), one previous transplant (OR 2.54, CI 1.75-3.68), life support (OR 3.68, CI 2.39-5.67), renal insufficiency (OR 2.66, CI 1.84-3.84), recipient weight under 6 kilograms (OR 1.67, CI 1.12-2.36) and cadaveric technical variant allograft (OR 1.38, CI 1.03-1.83). The Survival Outcomes Following Pediatric Liver Transplant score assigns weighted risk points to each of these factors in a scoring system to predict 3-month recipient survival after liver transplantation with a C-statistic of 0.74. Although quite accurate when compared with other posttransplant survival models, we would not advocate individual clinical application of the index.

Diverse epidemiological factors are associated with hepatocellular carcinoma (HCC) prevalence in different populations. However, the global landscape of the genetic changes in HCC genomes underpinning different epidemiological and ancestral backgrounds still remains uncharted. Here a collection of data from 503 liver cancer genomes from different populations uncovered 30 candidate driver genes and 11 core pathway modules. Furthermore, a collaboration of two large-scale cancer genome projects comparatively analyzed the trans-ancestry substitution signatures in 608 liver cancer cases and identified unique mutational signatures that predominantly contribute to Asian cases. This work elucidates previously unexplored ancestry-associated mutational processes in HCC development. A combination of hotspot TERT promoter mutation, TERT focal amplification and viral genome integration occurs in more than 68% of cases, implicating TERT as a central and ancestry-independent node of hepatocarcinogenesis. Newly identified alterations in genes encoding metabolic enzymes, chromatin remodelers and a high proportion of mTOR pathway activations offer potential therapeutic and diagnostic opportunities.

Although the incidence of caustic ingestion is declining, the management of caustic esophageal strictures remains a challenge. Mitomycin C (MMC) inhibits fibroblast proliferation and is effective in reducing scar in animal experiments. We report the case of a child with a distal esophageal stricture from lye ingestion managed with MMC. Despite repeated dilatations, at 1 year post injury, the stricture was 20% of esophageal diameter. Mitomycin C (4 microg/mL) was applied topically and circumferentially by endoscopy and repeated 4 months later. At 20 months follow-up, the child eats normally, and esophagram showed decreased stenosis (stricture was 50% of esophageal diameter). No complications were observed. Although controlled trials are required to confirm its efficacy, MMC should be considered as an adjunct in the management of caustic esophageal strictures in children.