Proceedings of the 28th Annual Congress of the International Liver Transplantation Society.

The 2023 Joint International Congress of the International Liver Transplantation Society (ILTS), the European Liver and Intestine Transplant Association (ELITA), and the Liver Intensive Care Group of Europe (LICAGE) held in Rotterdam, the Netherlands, marked a significant recovery milestone for the liver transplant community after COVID-19. With 1159 participants and a surge in abstract submissions, the event focused on "Liver Disorders and Transplantation: Innovations and Evolving Indications." This conference report provides a comprehensive overview of the key themes discussed during the event, encompassing Hepatology, Anesthesia and Critical Care, Acute Liver Failure, Infectious Disease, Immunosuppression, Pediatric Liver Transplantation, Living Donor Liver Transplantation, Transplant Oncology, Surgical Approaches, and Machine Perfusion. The congress provided a platform for extensive discussions on a wide range of topics, reflecting the continuous advancements and collaborative efforts within the liver transplant community.

A Protein-Protein Interaction Analysis Suggests a Wide Range of New Functions for the p21-Activated Kinase (PAK) Ste20.

The p21-activated kinases (PAKs) are important signaling proteins. They contribute to a surprisingly wide range of cellular processes and play critical roles in a number of human diseases including cancer, neurological disorders and cardiac diseases. To get a better understanding of PAK functions, mechanisms and integration of various cellular activities, we screened for proteins that bind to the budding yeast PAK Ste20 as an example, using the split-ubiquitin technique. We identified 56 proteins, most of them not described previously as Ste20 interactors. The proteins fall into a small number of functional categories such as vesicle transport and translation. We analyzed the roles of Ste20 in glucose metabolism and gene expression further. Ste20 has a well-established role in the adaptation to changing environmental conditions through the stimulation of mitogen-activated protein kinase (MAPK) pathways which eventually leads to transcription factor activation. This includes filamentous growth, an adaptation to nutrient depletion. Here we show that Ste20 also induces filamentous growth through interaction with nuclear proteins such as Sac3, Ctk1 and Hmt1, key regulators of gene expression. Combining our observations and the data published by others, we suggest that Ste20 has several new and unexpected functions.

Preventing Small-for-size Syndrome in Living Donor Liver Transplantation: Guidelines From the ILTS-iLDLT-LTSI Consensus Conference.

Small-for-size syndrome (SFSS) is a well-recognized complication following liver transplantation (LT), with up to 20% developing this following living donor LT (LDLT). Preventing SFSS involves consideration of factors before the surgical procedure, including donor and recipient selection, and factors during the surgical procedure, including adequate outflow reconstruction, graft portal inflow modulation, and management of portosystemic shunts. International Liver Transplantation Society, International Living Donor Liver Transplantation Group, and Liver Transplant Society of India Consensus Conference was convened in January 2023 to develop recommendations for the prediction and management of SFSS in LDLT. The format of the conference was based on the Grading of Recommendations, Assessment, Development, and Evaluation system. International experts in this field were allocated to 4 working groups (diagnosis, prevention, anesthesia, and critical care considerations, and management of established SFSS). The working groups prepared evidence-based recommendations to answer-specific questions considering the currently available literature. The working group members, independent panel, and conference attendees served as jury to edit and confirm the final recommendations presented at the end of the conference by each working group separately. This report presents the final statements and evidence-based recommendations provided by working group 2 that can be implemented to prevent SFSS in LDLT patients.

Proceedings of the 27th Annual Congress of the International Liver Transplantation Society.

After a virtual congress in 2021 and a previous absence in 2020 because of the coronavirus disease 2019 pandemic, the 27th Annual Congress of the International Liver Transplantation Society was held from May 4 to 7, 2022, in a hybrid format in Istanbul, with 1123 (58% on-site) liver transplant professionals from 61 countries attending the meeting. The hybrid format successfully achieved a balance of much yearned-for "in-person interaction" and global online participation. Almost 500 scientific abstracts were presented. In this report, the Vanguard Committee aims to present a summary of key invited lectures and selected abstracts for the liver transplant community.

Proceedings of the 26th Annual Virtual Congress of the International Liver Transplantation Society.

After a 1-y absence due to the coronavirus disease 2019 pandemic, the 26th Annual Congress of the International Liver Transplantation Society was held from May 15 to 18, 2021, in a virtual format. Clinicians and researchers from all over the world came together to share their knowledge on all the aspects of liver transplantation (LT). Apart from a focus on LT in times of coronavirus disease 2019, featured topics of this year's conference included infectious diseases in LT, living donation, machine perfusion, oncology, predictive scoring systems and updates in anesthesia/critical care, immunology, radiology, pathology, and pediatrics. This report presents highlights from invited lectures and a review of the select abstracts. The aim of this report, generated by the Vanguard Committee of International Liver Transplantation Society, is to provide a summary of the most recent developments in clinical practice and research in LT.

When is it safe for the liver donor to be discharged home and prevent unnecessary re-hospitalizations? - A systematic review of the literature and expert panel recommendations.

BACKGROUND: Few data are available on discharge criteria after living liver donation (LLD). OBJECTIVES: To identify the features for fit for discharge checklist after LLD to prevent unnecessary re-hospitalizations and to provide international expert recommendations. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. The critical outcomes included were complications rates and liver function (defined by elevated bilirubin and INR) (CRD42021260725). RESULTS: Total 57/1710 studies were included in qualitative analysis and 28/57 on the final analysis. No randomized controlled trials were identified. The complications rate was reported in 20/28 studies and ranged from 7.8% to 71.2%. Post hepatectomy liver function was reported in 13 studies. The Quality of Evidence (QoE) was Low and Very-Low for complications rate and liver function test, respectively. CONCLUSIONS: Monitoring and prevention of donor complications should be crucial in decision making of discharge. Pain and diet control, removal of all drains and catheters, deep venous thrombosis prophylaxis, and use routine imaging (CT scan or liver ultrasound) before discharge should be included as fit for discharge checklist (QoE; Low | GRADE of recommendation; Strong). Transient Impaired liver function (defined by elevated bilirubin and INR), a prognostic marker of outcome after liver resection, usually occurs after donor right hepatectomy and should be monitored. Improving trends for bilirubin and INR value should be observed by day 5 post hepatectomy and be included in the fit for discharge checklist. (QoE; Very-Low | GRADE; Strong).

Poor Antibody Response After Two Doses of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine in Transplant Recipients.

A low anti-spike antibody response of 28.6% was observed 28 days after BNT162b2 vaccine second dose among 133 solid organ transplant recipients without previous coronavirus disease 2019 (COVID-19). No serious adverse events were recorded. Four severe COVID-19 cases were reported between or after the 2 doses. Our data suggest to change the vaccine strategy.

Impact of sarcopenia on clinical outcomes of patients undergoing simultaneous liver and kidney transplantation: a cohort study.

BACKGROUND: The impact of sarcopenia in patients undergoing simultaneous liver and kidney transplantation (SLKT) has not been fully delineated. The aim of this single-centre-cohort-study was to evaluate the impact of sarcopenia on the clinical outcomes. METHODS: Between 2003 and 2018, 79 patients underwent SLKT. Sarcopenia was assessed via the total psoas muscle area (TPA) at the level of the 3rd. lumbar vertebra. Sarcopenia threshold was TPA < 1460 mm2 (women) and <1560 mm2 (men). We identified post-operative biliary, vascular and digestive complications. Survival analysis was performed by the Kaplan Meier method (log-rank test). RESULTS: We included 43/79 SLKT recipients (56%male, median age of 58 [53-63] years). The prevalence of cirrhosis was 74% (n = 32) with median MELD-score of 21 (20-22) and that of polycystic-liver-disease was 26% (n = 11). End-stage-renal-disease of unknown origin was 36.2% (n = 12). Dialysis before transplantation was performed in 54,8% (n = 23) of patients. The median TPA was 1138 (926-1510) mm2, and sarcopenia was detected in 72% of patients (n = 31). No difference in patient or death-censored graft-survival between sarcopenic and non-sarcopenic groups at 1 year was reported. Also, no differences at 6-months' post-transplant-complication-free and infection-free-survival rates were found. CONCLUSION: In this cohort of patients, no differences were observed in patients, grafts, complications or infection-free survival between sarcopenic or no sarcopenic SLKT patients. Future multi-centre studies are needed to validate and extend the generalisability of these findings.

Vena Cava and Pancreatic head En Bloc Resection for an Invasive Inferior Vena Cava Leiomyosarcoma in a Liver Transplant Patient.

BACKGROUND: De novo neoplasms are one of the major causes of death in patients after the first year of liver transplantation. The occurrence of sarcomas is extremely rare and the survival is often poor. However, early diagnosis and radical surgical treatment, may benefit some select liver transplant patients. METHOD: We describe the case of a liver transplant patient who developed a locally advanced inferior vena cava (IVC) leiomyosarcoma, who underwent radical surgical treatment with resection of the IVC associated with duodenopancreatectomy, right nephrectomy, and IVC reconstruction. We address aspects of the diagnosis and surgical strategy. CONCLUSION: This case report illustrates that IVC and multivisceral resections may be feasible and safe in highly selected liver transplant recipients. Major surgery should not be excluded as treatment option in an immunosuppressed liver transplant patient.

Covid-19 in liver transplant recipients: the French SOT COVID registry.

BACKGROUND: Notwithstanding the ongoing coronavirus disease-2019 (Covid-19) pandemic, information on its clinical presentation and prognosis in organ transplant recipients remains limited. The aim of this registry-based observational study was to report the characteristics and clinical outcomes of liver transplant (LT) recipients included in the French nationwide Registry of Solid Organ Transplant Recipients with Covid-19. METHODS: COVID-19 was diagnosed in patients who had a positive PCR assay for SARS-CoV-2 or in presence of typical lung lesions on imaging or specific SARS-CoV-2 antibodies. Clinical and laboratory characteristics, management of immunosuppression, treatment for Covid-19, and clinical outcomes (hospitalization, admission to intensive care unit, mechanical ventilation, or death) were recorded. RESULTS: Of the 104 patients, 67 were admitted to hospital and 37 were managed at home (including all 13 children). Hospitalized patients had a median age of 65.2 years (IQR: 58.1 - 73.2 years) and two thirds were men. Most common comorbidities included overweight (67.3%), hypertension (61.2%), diabetes (50.7%), cardiovascular disease (20.9%) and respiratory disease (16.4%). SARS-CoV-2 infection was identified after a median of 92.8 months (IQR: 40.1 - 194.7 months) from LT. During hospitalization, antimetabolites, mTOR inhibitor, and CNIs were withdrawn in 41.9%, 30.0% and 12.5% of patients, respectively. The composite endpoint of severe Covid-19 within 30 days after diagnosis was reached by 33.0% of the adult patients. The 30-day mortality rate was 20.0%, and 28.1% for hospitalized patients. Multivariate analysis identified that age was independently associated with mortality. CONCLUSION: In our large nationwide study, Covid-19 in LT recipients was associated with a high mortality rate.

Biliary complications after liver transplantation: current perspectives and future strategies.

IMPORTANCE: Liver transplantation (LT) is a life-saving therapy for patients with end-stage liver disease and with acute liver failure, and it is associated with excellent outcomes and survival rates at 1 and 5 years. The incidence of biliary complications (BCs) after LT is reported to range from 5% to 20%, most of them occurring in the first three months, although they can occur also several years after transplantation. OBJECTIVE: The aim of this review is to summarize the available evidences on pathophysiology, risk factors, diagnosis and therapeutic management of BCs after LT. EVIDENCE REVIEW: a literature review was performed of papers on this topic focusing on risk factors, classifications, diagnosis and treatment. FINDINGS: Principal risk factors include surgical techniques and donor's characteristics for biliary leakage and anastomotic biliary strictures and vascular alterations for non- anastomotic biliary strictures. MRCP is the gold standard both for intra- and extrahepatic BCs, while invasive cholangiography should be restricted for therapeutic uses or when MRCP is equivocal. About treatment, endoscopic techniques are the first line of treatment with success rates of 70-100%. The combined success rate of ERCP and PTBD overcome 90% of cases. Biliary leaks often resolve spontaneously, or with the positioning of a stent in ERCP for major bile leaks. CONCLUSIONS AND RELEVANCE: BCs influence morbidity and mortality after LT, therefore further evidences are needed to identify novel possible risk factors, to understand if an immunological status that could lead to their development exists and to compare the effectiveness of innovative surgical and machine perfusion techniques.

Acute liver failure and HELLP syndrome: A clinical case and literature review.

BACKGROUND: HELLP syndrome is a pregnancy-related liver disease associated with increased maternal and foetal mortality. In rare cases, it can lead to the development of a subcapsular hepatic haematoma as well as its rupture. This rupture is life-threatening if not urgently treated. METHOD: We describe a clinical case of HELLP syndrome involving a ruptured subcapsular liver haematoma and contextualise this with a literature overview. CLINICAL CASE: A 39-year-old woman of 40 weeks' gestation presented to her local Emergency Department with symptoms and serology classically associated with HELLP syndrome. However, she clinically deteriorated and developed a ruptured subcapsular haematoma. She underwent an emergency Caesarean section at her initial hospital. Upon clinical stabilisation, she was transferred to our transplant unit for an urgent liver transplant. CONCLUSION: LT is a life-saving procedure for patients with acute liver failure secondary to HELLP syndrome. These patients should be immediately referred to a high-volume transplant centre.

Consequences of Extended Spectrum Beta-Lactamase-Producing Enterobacteriaceae and Methicillin-Resistant Staphylococcus aureus Carriage in Awaiting Liver Transplant Patients.

Infections in patients with cirrhosis are associated with liver-related complications (LRCs), especially in patients awaiting liver transplantation (LT). The aim of this study was to evaluate the impact of methicillin-resistant Staphylococcus aureus (MRSA) and extended spectrum beta-lactamase colonization on infections and LRCs for patients on the wait list and on infections after LT. We retrospectively included 250 of 483 patients with cirrhosis who were placed on the wait list for LT from December 2015 to January 2018. These patients were screened for MRSA or extended spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) at the time of wait-list placement and after LT. Of the patients, 76% were male with a mean age of 57.5 ± 10 years, and the most frequent cause of liver disease was alcohol (39%). Median Model for End-Stage Liver Disease (MELD) score was 19 (12-28). Only 1 patient was positive for MRSA; 19% of patients (n = 47) had ESBLE fecal carriage at the time of wait-list placement and 15% (n = 37) had it after LT. Infection-free survival on the wait list and after LT, according to fecal carriage status, was not statistically different between 2 groups. LRC-free survival at 6 and 12 months was significantly lower in ESBLE fecal carriage (HR, 1.6; P = 0.04). MELD score >19 (HR, 3.0; P = 0.01) and occurrence of infection during the first 3 months on the wait list (HR, 4.13; P < 0.001) were independent risk factors for LRC occurrence in the multivariate analysis. Our study is the first showing that in a cohort of patients with cirrhosis waiting for LT LRC-free survival was lower in patients with ESBLE fecal carriage but that infection-free survival was not different between the 2 groups.

COVID-19 in a liver transplant recipient: Could iatrogenic immunosuppression have prevented severe pneumonia? A case report.

BACKGROUND: Coronavirus disease (COVID) is a new and highly contagious infectious disease caused by the coronavirus (COVID-19 or severe acute respiratory syndrome coronavirus 2). There is limited data regarding the incidence and management of COVID-19 in immunocompromised patients' post-transplantation. In the pre-COVID-19 era, these patients were already at an increased risk of developing opportunistic infections. These often manifested with atypical symptoms. CASE SUMMARY: We report another case of uneventful COVID-19 pneumonia in a 58-year old male who was 18 mo' post liver transplantation. He received tacrolimus monotherapy since July 2019. The clinical manifestations included only epigastric pain radiating to the right hypochondrium, nausea and vomiting. He had no fevers, cough, shortness of breath, anosmia or dysgeusia even if the chest computed tomography scan revealed an extension of the multiple patchy ground-glass density shadows to the upper lobe of the left lung too. He was hospitalised and received a course of oral chloroquine (200 mg × 3 per day) for a period of 10 d. Interestingly, the COVID 19 infection was uneventful though there were no modifications to his tacrolimus dosing. He was successfully discharged. We performed subsequent follow-up via telemedicine. CONCLUSION: In light of the current pandemic, it is even more important to identify how the liver recipient's patients present and are managed, especially for immunosuppression treatment.

Exploration of the physiological response to an online gambling task by frequency domain analysis of the electrodermal activity.

Online gambling has dramatically increased over the last decades, thus the study of the underlying physiological mechanisms could be helpful to better understand related disorders. Specifically, physiological arousal is well-known to play a key role in gambling behavior. In the present study, unconventional frequency feature of the electrodermal activity (EDA) was extracted (EDASympn) and compared to the most common heart rate variability (HRV) spectral parameters (LF, HF, HFn, LF/HF) to measure arousal during an online gambling session. 46 subjects played online slot machines for 30 minutes, while EDA and ECG were recorded. In the analysis the gaming session was divided into three 10-minutes-long phases. A one-way repeated measures analysis of variance was carried out for each spectral parameter, with the game phases as within-subjects factor. All the calculated parameters showed significant differences between the initial phase of the game and the last two (p < 0.001). In particular, EDAsympn displayed a reciprocal trend with respect to HFn: an initial increase (decrease for HFn) was followed by a plateau phase. LF exhibited a significant difference also between the second and the third phases. EDA frequency-domain analysis appears to be a promising method for physiological arousal assessment, by showing the same discriminative power of HRV spectral components. Further research is needed to emphasize these findings.Clinical Relevance-This promotes the use of a new and easy-to-implement method to assess sympathetic activity.

Transient increase of CA 19-9 serum concentrations in a liver transplant recipient with cystic fibrosis and hepatic abscess: a case report and brief literature review.

CA 19-9 (carbohydrate antigen 19-9) is a tumor marker widely used for surveillance of patients with pancreatic cancer. However, even high levels of CA 19-9 may not necessarily be cancer-associated thereby complicating the diagnosis. This case report highlights a transient increase of CA 19-9 in a triple transplanted patient with cystic fibrosis and continuous immunosuppression for 20 years who was under antibiotics. This case emphasizes the need for a balanced interpretation of biological results, especially in cases where many confounding factors are present such as diabetes, chronic renal failure, cystic fibrosis and infections. This case also provides an opportunity to formulate a number of recommendations for the interpretation of tumor marker results in order to avoid long and costly further investigations.

Longterm Risk of Solid Organ De Novo Malignancies After Liver Transplantation: A French National Study on 11,226 Patients.

De novo malignancies are one of the major late complications and causes of death after liver transplantation (LT). Using extensive data from the French national Agence de la Biomédecine database, the present study aimed to quantify the risk of solid organ de novo malignancies (excluding nonmelanoma skin cancers) after LT. The incidence of de novo malignancies among all LT patients between 1993 and 2012 was compared with that of the French population, standardized on age, sex, and calendar period (standardized incidence ratio; SIR). Among the 11,226 LT patients included in the study, 1200 de novo malignancies were diagnosed (10.7%). The risk of death was approximately 2 times higher in patients with de novo malignancy (48.8% versus 24.3%). The SIR for all de novo solid organ malignancies was 2.20 (95% confidence interval [CI], 2.08-2.33). The risk was higher in men (SIR = 2.23; 95% CI, 2.09-2.38) and in patients transplanted for alcoholic liver disease (ALD; SIR = 2.89; 95% CI, 2.68-3.11). The cancers with the highest excess risk were laryngeal (SIR = 7.57; 95% CI, 5.97-9.48), esophageal (SIR = 4.76; 95% CI, 3.56-6.24), lung (SIR = 2.56; 95% CI, 2.21-2.95), and lip-mouth-pharynx (SIR = 2.20; 95% CI, 1.72-2.77). In conclusion, LT recipients have an increased risk of de novo solid organ malignancies, and this is strongly related to ALD as a primary indication for LT.