Etiology, Characteristics, and Outcomes of Neonatal Liver Failure: Lessons Learned Over the Last 3 Decades.

OBJECTIVE: To evaluate trends in etiology and outcomes of neonatal liver failure (NLF) over 30 years retrospectively at a single institution. STUDY DESIGN: Inclusion criteria for this retrospective cohort study were babies presenting at a chronological age of ≤28 days between 1991 and 2020 with prothrombin time ≥20 seconds and biochemical liver injury. Demographics, etiology, laboratory investigations, need for extrahepatic organ support, acute kidney injury, and intervention with liver transplant (LT) were recorded. Survival outcomes were measured as discharge from the hospital alive with native liver or LT. The study period was stratified into 3 10-year blocks. Trends were analyzed for hospital admissions, etiology, and survival outcomes. RESULTS: One hundred twenty-six babies met the NLF criteria. Admissions to the hospital increased from 21 in 1991-2000 to 65 in 2011-2020. An increasing trend in infectious and metabolic causes, while a decreasing trend in indeterminate etiology, was noted. Survival with native liver improved from 23.8% in 1991-2000 to 55.4% in 2011-20 (P = .021), and mortality reduced from 52.4% to 35.4% during the same periods (P = .213). Twenty-three (18.2%) neonates received LT. Post-LT survival outcomes were 100% for gestational alloimmune liver disease, 66.6% in the indeterminate group, and 25% for herpes simplex virus. Specific etiologies (gestational alloimmune liver disease, OR = 0.07 [0-0.77, P = .048]), presence of acute kidney injury (OR = 6.22 [1.45, 29.38, P = .015]) and need for inotropes (OR = 6.22 [1.45, 29.38, P = .028]) influenced mortality in multivariable logistic regression analysis. CONCLUSIONS: In the last 30 years, advances in diagnosis, treatment, and increasing experience with LT have improved survival in NLF.

Predictors of patient and graft survival following pediatric liver transplantation: Long-term analysis of more than 300 cases from single centre.

BACKGROUND: Pediatric liver transplant (PLT) activity has flourished over time although with limited expansion in the graft pool. The study aims to identify pre-transplant factors that predict post-transplant patient and graft survival in the PLT population. METHODS: Retrospective review of PLTs at a single tertiary transplant unit from 2000 to 2019. Univariate and multivariate analyses of pre-transplant factors were performed to identify predictors of patient and graft survival. RESULTS: Two hundred and seventy-six patients received 320 PLTs. The most common cause of graft loss was hepatic artery thrombosis (n = 13, 29.6%). The most common cause of mortality was sepsis (n = 11, 29.7%). Univariate analysis showed that the following variables had a significant (p < .05) impact on patient survival: recipient age, weight, height, graft type (technical variant graft), transplant category (acute liver failure), the era of transplant, and invasive ventilation. The following variables had a significant (p < .05) impact on graft survival: recipient age, weight, height, transplant category (acute liver failure), and the era of transplant. Multivariate analysis precluded the era of transplant as the only significant factor for patient survival; patients transplanted after 2005 had significantly higher patient survival. No independent factor predicting graft survival was identified. For children transplanted after 2005, the only factor that predicted patient survival was pre-transplant invasive ventilation. CONCLUSIONS: Our study suggests that the learning curve and pre-transplant invasive ventilation in the recipient have a significant impact on patient survival. The traditional view of worse outcomes of smaller PLT candidates should be changed.

Long-term outcomes of pediatric liver transplantation using organ donation after circulatory death: Comparison between full and reduced grafts.

BACKGROUND: The shortage of donors' livers for pediatric recipients inspired the search for alternatives including donation after cardiac death (DCD). METHODS: Retrospective review of pediatric liver transplant (PLT) using DCD grafts. Patients were divided into either FLG or RLG recipients. Pre-transplant recipient parameters, donor parameters, operative parameters, post-transplant recipient parameters, and outcomes were compared. RESULTS: Overall, 14 PLTs from DCD donors between 2005 and 2018 were identified; 9 FLG and 5 RLG. All donors were Maastricht category III. Cold ischemia time was significantly longer in RLG (8.2 h vs. 6.2 h; p = .038). Recipients of FLG were significantly older (180 months vs. 7 months; p = .012) and waited significantly longer (168 days vs. 22 days; p = .012). Recipients of RLG tended to be sicker in the immediate pre-transplant period and this was reflected by the need for respiratory or renal support. There was no significant difference between groups regarding long-term complications. Three patients in each group survived more than 5 year post-transplant. One child was re-transplanted in the RLG due to portal vein thrombosis but failed to survive after re-transplant. One child from FLG also died from a non-graft-related cause. CONCLUSIONS: Selected DCD grafts are an untapped source to widen the donor pool, especially for sick recipients. In absence of agreed criteria, graft and recipient selection for DCD grafts should be undertaken with caution.

The Broad Spectrum of Paediatric Pancreatic Disease: A Single-center 26-years Retrospective Review.

BACKGROUND: Paediatric pancreatic pathology and its management is rarely described. We present our experience. METHODS: A retrospective case-note review of all patients with pancreatic disease from 1995 to 2021 was completed. Data are quoted as median (range). RESULTS: Two hundred and twelve patients were identified with 75.9% presenting with pancreatitis. Referrals for pancreatitis increased during the study period and affected a wide age range (2 months-15.6 years). Acute pancreatitis (n = 118) (age 10.6 (0.18-16.3) years). The most common causes were idiopathic (n = 60, 50.8%) and biliary (n = 28, 23.8%). About 10% required treatment for complications or underlying biliary causes. Recurrent pancreatitis (n = 14) (11.6 (0.3-14.3) years). The most common cause was hereditary pancreatitis (n = 6, 42.9%). One patient required endoscopic drainage of pseudocyst. Chronic pancreatitis (n = 29) (16 (0.38-15.5) years). The underlying diagnosis was idiopathic (n = 14, 48.4%) or hereditary pancreatitis (n = 10, 34.5%). 13 patients required active management, including pancreaticojejunostomies (n = 5). Blunt Trauma (n = 34) was managed conservatively in 24 (70.5%). 6 patients required open surgery, but 4 were managed by either endoscopy or interventional radiology. Pancreatic tumours (n = 13) presented at 11.2 (2.3-16) years. Pathology included pancreaticoblastomas (n = 3), solid pseudopapillary tumours (n = 3), neuroendocrine tumours (n = 2), acinar cell cystadenoma (n = 1), intraductal papillary mucinous neoplasm (n = 1), pancreatic insulinoma (n = 1), pancreatic ductal adenocarcinoma (n = 1), and embryonal rhabdomyosarcoma (n = 1). OTHERS (N = 4): Pancreatic cyst (n = 3) and annular pancreas (n = 1). CONCLUSION: Paediatric pancreatic disease spans a wide spectrum of both benign and malignant disease and benefits from access to specialist medical, surgical, endoscopic, and interventional radiology expertise. Referrals for paediatric pancreatitis are increasing, but aetiology is different to that seen in adults. LEVEL OF EVIDENCE: IV.

Impact of Donor Obesity on Graft and Recipient Survival Outcomes After Liver Transplantation: A Systematic Review and Meta-analysis.

Background: The effect of donor body mass index (BMI) on liver transplantation (LT) outcomes remains unclear. Methods: A systematic search of the MEDLINE, CENTRAL, Web of Science, and bibliographic reference lists was conducted. All comparative studies evaluating the outcomes of LT in obese (BMI > 30 kg/m2) and nonobese donors (BMI < 30 kg/m2) were included, and their risk of bias was assessed using the ROBINS-I assessment tool. Patient and graft survival, acute rejection, and graft failure requiring retransplantation were evaluated as outcome parameters. A random-effects model was used for outcome synthesis. Results: We included 6 comparative studies reporting a total of 5071 liver transplant recipients from 708 obese and 4363 nonobese donors. There was no significant difference in 1-y (89.1% versus 84.0%, odds ratio [OR] 1.58; 95% CI 0.63-3.94, P = 0.33), 5-y (74.2%% versus 73.5%, OR 1.12; 95% CI 0.45-2.80, P = 0.81) graft survival, and 1-y (87.1% versus 90.3%, OR 0.71; 95% CI 0.43-1.15, P = 0.17) and 5-y (64.5% versus 71.6%, OR 0.71; 95% CI 0.49-1.05, P = 0.08) patient survival between 2 groups. Furthermore, recipients from obese and nonobese donors had a comparable risk of graft failure requiring retransplantation (OR 0.92; 95% CI 0.33-2.60, P = 0.88) or acute graft rejection (OR 0.70; 95% CI 0.45-1.11, P = 0.13). Conclusions: A meta-analysis of the best available evidence (level 2a) demonstrates that donor obesity does not seem to have a negative impact on graft or patient outcomes. The available studies might be subject to selection bias as the grafts from obese donors are usually subject to biopsy to exclude steatosis and the recipients usually belong to the low-risk group. Future research is needed to evaluate the impact of donors subgrouped by various higher BMI on graft and patient-related outcomes as well as to capture data of the discarded grafts from obese donors; hence, selection criteria for the grafts that could be used for transplantation from obese donors is identified.

SIMAP500: A novel risk score to identify recipients at higher risk of hepatocellular carcinoma recurrence following liver transplantation.

BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) has a devastating influence on recipients' survival; however, the risk of recurrence is not routinely stratified. Risk stratification is vital with a long LT waiting time, as that could influence the recurrence despite strict listing criteria. AIM: This study aims to identify predictors of recurrence and develop a novel risk prediction score to forecast HCC recurrence following LT. METHODS: A retrospective review of LT for HCC recipients at University Hospitals Birmingham between July 2011 and February 2020. Univariate and multivariate analyses were performed to identify recurrence predictors, based on which the novel SIMAP500 (satellite nodules, increase in size, microvascular invasion, AFP > 500, poor differentiation) risk score was proposed. RESULTS: 234 LTs for HCC were performed with a median follow-up of 5.3 years. Recurrence developed in 25 patients (10.7%). On univariate analyses, RETREAT score > 3, α-fetoprotein (AFP) at listing 100-500 and > 500, bridging, increased tumour size between imaging at the listing time and explant histology, increase in the size of viable tumour between listing and explant, presence of satellite nodules, micro- and macrovascular invasion on explant and poor differentiation of tumours were significantly associated with recurrence, based on which, the SIMAP500 risk score is proposed. The SIMAP500 demonstrated an excellent predictive ability (c-index = 0.803) and outperformed the RETREAT score (c-index = 0.73). SIMAP500 is indicative of the time to disease recurrence. CONCLUSION: SIMAP500 risk score identifies the LT recipients at risk of HCC recurrence. Risk stratification allows patient-centric post-transplant surveillance programs. Further validation of the score is recommended.

Long-term outcomes of pediatric liver transplantation in acute liver failure vs end-stage chronic liver disease: A retrospective observational study.

BACKGROUND: Children with acute liver failure (ALF) who meet the criteria are eligible for super-urgent transplantation, whereas children with end-stage chronic liver disease (ESCLD) are usually transplanted electively. Pediatric liver trans plantation (PLT) in ALF and ESCLD settings has been well described in the literature, but there are no studies comparing the outcomes in these two groups. AIM: To determine if there is a difference in post-operative complications and survival outcomes between ALF and ESCLD in PLT. METHODS: This was a retrospective observational study of all primary PLTs performed at a single center between 2000 and 2019. ALF and ESCLD groups were compared for pretransplant recipient, donor and operative parameters, and post-operative outcomes including graft and patient survival. RESULTS: Over a 20-year study period, 232 primary PLTs were performed at our center; 195 were transplanted for ESCLD and 37 were transplanted for ALF. The ALF recipients were significantly older (median 8 years vs 5.4 years; P = 0.031) and heavier (31 kg vs 21 kg; P = 0.011). Living donor grafts were used more in the ESCLD group (34 vs 0; P = 0.006). There was no difference between the two groups concerning vascular complications and rejection, but there were more bile leaks in the ESCLD group. Post-transplant patient survival was significantly higher in the ESCLD group: 1-, 5-, and 10-year survival rates were 97.9%, 93.9%, and 89.4%, respectively, compared to 78.3%, 78.3%, and 78.3% in the ALF group (P = 0.007). However, there was no difference in 1-, 5-, and 10-year graft survival between the ESCLD and ALF groups (90.7%, 82.9%, 77.3% vs 75.6%, 72.4%, and 66.9%; P = 0.119). CONCLUSION: Patient survival is inferior in ALF compared to ESCLD recipients; the main reason is death in the 1st year post-PLT in ALF group. Once the ALF children overcome the 1st year after transplant, their survival stabilizes, and they have good long-term outcomes.

COVID-19 Vaccine Acceptance among Social Media Users: A Content Analysis, Multi-Continent Study.

Vaccine hesitancy (VH) is defined as a delayed in acceptance or refusal of vaccines despite availability of vaccination services. This multinational study examined user interaction with social media about COVID-19 vaccination. The study analyzed social media comments in 24 countries from five continents. In total, 5856 responses were analyzed; 83.5% of comments were from Facebook, while 16.5% were from Twitter. In Facebook, the overall vaccine acceptance was 40.3%; the lowest acceptance rates were evident in Jordan (8.5%), Oman (15.0%), Senegal (20.0%) and Morocco (20.7%) and the continental acceptance rate was the lowest in North America 22.6%. In Twitter, the overall acceptance rate was (41.5%); the lowest acceptance rate was found in Oman (14.3%), followed by USA (20.5%), and UK (23.3%) and the continental acceptance rate was the lowest in North America (20.5%), and Europe (29.7%). The differences in vaccine acceptance across countries and continents in Facebook and Twitter were statistically significant. Regarding the tone of the comments, in Facebook, countries that had the highest number of serious tone comments were Sweden (90.9%), USA (61.3%), and Thailand (58.8%). At continent level, serious comments were the highest in Asia (58.4%), followed by Africa (46.2%) and South America (46.2%). In Twitter, the highest serious tone was reported in Egypt (72.2%) while at continental level, the highest proportion of serious comments was observed in Asia (59.7%), followed by Europe (46.5%). The differences in tone across countries and continents in Facebook and Twitter and were statistically significant. There was a significant association between the tone and the position of comments. We concluded that the overall vaccine acceptance in social media was relatively low and varied across the studied countries and continents. Consequently, more in-depth studies are required to address causes of such VH and combat infodemics.

Paediatric Liver Transplantation During COVID-19 Pandemic: Lessons Learned and Unanswered Questions.

COVID-19 pandemic has imposed many challenges on paediatric liver transplantation (PLT) services and has necessitated several adaptations in different stages of the process to ensure transplant centres can still deliver the proposed services in addition to protecting patients and staff against infection. This review article digs through the current literature to clarify the challenges imposed by SARS-CoV2 on PLT centres globally. It provides an overview of current practice as well as suggestions from experts in the field to overcome multiple obstacles. In paediatrics, the reaction to SARS-CoV2 may be less severe than that seen in the adult population, but this can change in view of newly discovered virus strains. Response of transplant centres to the current pandemic was variable depending on the anticipated risk and available resources. Telemedicine has helped PLT programmes to continue their activities while protecting patients, as well as staff against the risk of SARS-CoV2 virus. Further studies are needed to guide immunosuppression management in post-transplant infected candidates; answering this critical question will help PLT centres solve this dilemma.

Arabic validation and cross-cultural adaptation of the 5C scale for assessment of COVID-19 vaccines psychological antecedents.

BACKGROUND: In the Arab countries, there has not been yet a specific validated Arabic questionnaire that can assess the psychological antecedents of COVID-19 vaccine among the general population. This study, therefore, aimed to translate, culturally adapt, and validate the 5C scale into the Arabic language. METHODS: The 5C scale was translated into Arabic by two independent bilingual co-authors, and then translated back into English. After reconciling translation disparities, the final Arabic questionnaire was disseminated into four randomly selected Arabic countries (Egypt, Libya, United Arab Emirates (UAE), and Saudi Arabia). Data from 350 Arabic speaking adults (aged ≥18 years) were included in the final analysis. Internal consistency was assessed by Cronbach's alpha. Construct validity was determined by concurrent, convergent, discriminant, exploratory and confirmatory factor analyses. RESULTS: Age of participants ranged between 18 to 73 years; 57.14% were females, 37.43% from Egypt, 36.86%, from UAE, 30% were healthcare workers, and 42.8% had the intention to get COVID-19 vaccines. The 5 sub-scales of the questionnaire met the criterion of internal consistency (Cronbach's alpha ≥0.7). The predictors of intention to get COVID-19 vaccines (concurrent validity) were young age and the 5C sub-scales. Convergent validity was identified by the significant inter-item and item-mean score of the sub-scale correlation (P<0.001). Discriminant validity was reported as inter-factor correlation matrix (<0.7). Kaiser-Meyer-Olkin sampling adequacy measure was 0.80 and Bartlett's sphericity test was highly significant (P<0.001). Exploratory factor analysis indicated that the 15 items of the questionnaire could be summarized into five factors. Confirmatory factor analysis confirmed that the hypothesized five-factor model of the 15-item questionnaire was satisfied with adequate psychometric properties and fit with observed data (RMSEA = 0.060, GFI = 0.924, CFI = 0.957, TLI = 0.937, SRMR = 0.076 & NFI = 906). CONCLUSION: The Arabic version of the 5C scale is a valid and reliable tool to assess the psychological antecedents of COVID-19 vaccine among Arab population.