1Department of Medicine, Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Aurora, Colorado, USA 2Colorado Center for Transplantation Care, Research, and Education (CCTCARE), University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA Abbreviations: DiD, difference-in-difference; LT, liver transplantation. Correspondence Michael Kriss, Department of Medicine, Division of Gastroenterology & Hepatology, 12700 East 19th Avenue, Campus Box B146, Aurora, Colorado 80045, USA. Email: [email protected]

1Liver ICU, Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS and CIBERehd, Spain 2EF Clif, EASL-CLIF Consortium, Barcelona, Spain 3Department of Hemotherapy and Hemostasis, Apheresis & Cellular Therapy Unit, ICMHO, Hospital Clínic de Barcelona, Barcelona, Spain, IDIBAPS, Barcelona, Spain. University of Barcelona, Barcelona, Spain Abbreviations: ACLF, acute-on-chronic liver failure; ALF, acute liver failure; LT, liver transplantation; PE, plasma exchange; RCT, randomized controlled trial. Correspondence Javier Fernandez, Liver Unit, Hospital Clínic, Villarroel 170, 08036, Barcelona, Spain. Email: [email protected]

Di Francesco, Fabrizio; Vella, Roberta; Calandrino, Giorgia; Accardo, Caterina; Vella, Ivan; Gruttadauria, Salvatore Author Information

Division of Transplantation, CLINTEC, Karolinska Institutet, Stockholm, Karolinska University Hospital, Stockholm Abbreviations: cDCD, controlled donation after circulatory death; DCD, donation after circulatory death; MP, machine perfusion; NRP, normothermic regional perfusion; PRS, postreperfusion syndrome; uDCD, uncontrolled DCD. Correspondence Gabriel C. Oniscu, Professor of Transplantation Surgery, Division of Transplantation, CLINTEC, Karolinska Institutet, Stockholm, Sweden. Email: [email protected]

1University of Colorado, Pediatrics; Children's Hospital Colorado, Pediatric Gastroenterology, Hepatology, and Nutrition, Aurora, Colorado, USA 2Children's Hospital Colorado, University of Colorado, School of Medicine, Pediatrics, Aurora, Colorado USA Abbreviation: TSMI, total skeletal muscle index. Correspondence Shikha S. Sundaram, Children's Hospital Colorado, University of Colorado School of Medicine, 13123 East 16th Ave, B290, Aurora, CO 80045. Email: [email protected]

Division of Gastroenterology & Hepatology, University of California at San Diego, La Jolla, California, USA Abbreviations: CAD, coronary artery disease; CAD-RADS, Coronary Artery Disease-Reporting and Data System; CTCA, computed tomography coronary angiography; MACE, major adverse cardiovascular events; MAFLD, metabolic associated liver disease; MASH, metabolic dysfunction -associated steatohepatitis; PCI, percutaneous coronary intervention; TTE, transthoracic echocardiogram. Correspondence Monica Tincopa, UCSD Division of Gastroenterology & Hepatology, 9350 Campus Point Drive, San Diego, CA 92037, USA. Email: [email protected]

To the editor, Glinka et al’s review of liver transplantation after medical assistance in dying adds to the ever-growing literature from countries and states where voluntary assisted dying (VAD) or euthanasia is legal.1 Outcomes are good, and warm ischemic times are short; clearly, it works. However, opinions are likely to be as divided as those pertaining to the ethics of VAD itself. For hepatologists, the discussion is further layered by a compelling need to expand the donor pool and prolong the lives of patients with liver failure. Ray and Martin have reported that in 2020, 4% of donations followed euthanasia or VAD in the Netherlands and Canada.2 This expansion is highly significant and is no longer theoretical. It is occurring across the globe by degrees, but society chairs, thought leaders, and journal editors have not yet opined, leaving somethin g of a moral and ethical vacuum for clinicians who must now decide what stance to take. Although this is not the place to rehearse all the arguments for and against organ donation after VAD, the “dead donor rule” tends to dominate the discussion. This mandates that organs are only taken from the dead, protecting individuals from harm and society from a dystopian end point.3 The boundary between life and death becomes blurred when death is brought about by the removal of vital organs that are to be donated (so-called organ donation euthanasia).4 It has been argued that patient autonomy should not extend this far due to the wider societal consequences.5 This is but one example of many challenging ethical debates that the transplant community must work through in advance of a growing phenomenon. If guidance, structures, and safeguards are not put in place, we will see variation in practice—a sure sign that risks of injustice and inequity exist.

An ischemia-reperfusion injury (IRI) results from a prolonged ischemic insult followed by the restoration of blood perfusion, being a common cause of morbidity and mortality, especially in liver transplantation. At the maximum of the potential damage, IRI is characterized by 2 main phases. The first is the ischemic phase, where the hypoxia and vascular stasis induces cell damage and the accumulation of damage-associated molecular patterns and cytokines. The second is the reperfusion phase, where the local sterile inflammatory response driven by innate immunity leads to a massive cell death and impaired liver functionality. The ischemic time becomes crucial in patients with underlying pathophysiological conditions. It is possible to compare this process to a shooting gun, where the loading trigger is the ischemia period and the firing shot is the reperfusion phase. In this optic, this article aims at reviewing the main ischemic events following the phases of the surgical timeline, considering the consequent reperfusion damage.

To the editor, We read with great interest the recent study conducted by Patel et al,1 in which they shed light on the alarmingly low rate (14.3%) of early diagnostic paracentesis (within 24 h) performed on cirrhosis patients admitted with ascites. The study revealed an association between delayed paracentesis and adverse outcomes such as intensive care unit admission, acute kidney injury, and mortality. These findings reinforce previous research that consistently demonstrates the disappointingly low adherence to guidelines regarding early paracentesis.2,3 Within our own unit, we conducted an audit and found that only 16% of the patients admitted with ascites underwent diagnostic paracentesis within 12 hours of admission.4 Through this evaluation, we identified knowledge gaps among junior doctors regarding indications for paracentesis, lack of procedural experience, and inadequate access to ultrasound as predominant factors contributing to delayed paracentesis. In response, we devised and implemented a comprehensive paracentesis training program that encompassed didactic lectures, hands-on training utilizing a portable ultrasound device, and paracentesis simulation models. To date, 48 trainees have undergone the program, over half being within their first 2 years of postgraduate training. To gauge the impact of this initiative, we evaluated the trainees’ comprehension by comparing pretutorial and post-tutorial assessments focused on the fundamental principles of performing a paracentesis procedure and diagnosing spontaneous bacterial peritonitis. Statistical analysis through a Wilcoxon signed rank test revealed a significantly higher median score of 5 post-tutorial compared to the pretutorial score of 2 (p < 0.001). In summary, we congratulate Patel and colleagues for their excellent study, as it brings attention to the concerning issue of delayed diagnostic paracentesis. We firmly believe that broader implementation of structured paracentesis training programs, akin to the one we designed, could effectively increase rates of early paracentesis and potentially reduce avoidable harm.