The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has a drastic impact on national health care systems. Given the overwhelming demand on facility capacity, the impact on all health care sectors has to be addressed.Solid organ transplantation represents a field with a high demand on staff, intensive care units, and follow-up facilities. The great therapeutic value of organ transplantation has to be weighed against mandatory constraints of health care capacities. In addition, the management of immunosuppressed recipients has to be reassessed during the ongoing coronavirus disease 2019 (COVID-19) pandemic. In addressing these crucial questions, transplant physicians are facing a total lack of scientific evidence.Therefore, the aim of this study was to offer an approach of consensus-based guidance, derived from individual information of 22 transplant societies. Key recommendations were extracted and the degree of consensus among different organizations was calculated. A high degree of consensus was found for temporarily suspending nonurgent transplant procedures and living donation programs. Systematic polymerase chain reaction-based testing of donors and recipients was broadly recommended.Additionally, more specific aspects (eg, screening of surgical explant teams and restricted use of marginal donor organs) were included in our analysis. This study offers a novel approach to informed guidance for health care management when a priori no scientific evidence is available.

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The Model for End-Stage Liver Disease (MELD)-based allocation system was implemented in Germany in 2006 in order to reduce waiting list mortality. The purpose of this study was to evaluate post-transplant results and waiting list mortality since the introduction of MELD-based allocation in our center and in Germany. Adult liver transplantation at the Charité—Universitätsmedizin Berlin was assessed retrospectively between 2005 and 2012. In addition, open access data from Eurotransplant (ET) and the German Organ Transplantation Foundation (DSO) were evaluated. In our department, 861 liver transplantations were performed from 2005 to 2012. The mean MELD score calculated with the laboratory values last transmitted to ET before organ offer (labMELD) at time of transplantation increased to 20.1 from 15.8 (Pearson’s R = 0.121, p < 0.001, confidence interval (CI) = 0.053–0.187). Simultaneously, the number of transplantations per year decreased from 139 in 2005 to 68 in 2012. In order to overcome this organ shortage the relative number of utilized liver donors in Germany has increased (85% versus 75% in non-German ET countries). Concomitantly, 5-year patient survival decreased from 79.9% in 2005 to 60.3% in 2012 (p = 0.048). At the same time, the ratio of waiting list mortality vs. active-listed patients nearly doubled in Germany (Spearman’s rho = 0.903, p < 0.001, CI = 0.634–0.977). In low-donation areas, MELD-based liver allocation may require reconsideration and inclusion of prognostic outcome factors.

Donor organ quality is crucial for transplant survival and long-term survival of patients after liver transplantation. Besides bacterial and viral infections, endogenous damage-associated molecular patterns (DAMPs) can stimulate immune responses. Cell-free DNA (cfDNA) is one such DAMP that exhibits highly proinflammatory effects via DNA sensors. Herein, we measured cfDNA after liver transplantation and found elevated levels when organs from resuscitated donors were transplanted. High levels of cfDNA were associated with high C-reactive protein, leukocytosis as well as granulocytosis in the recipient. In addition to increased systemic immune responses, portal hepatitis was observed, which was associated with increased interface activity and a higher numbers of infiltrating neutrophils and eosinophils in the graft. In fact, the cfDNA was an independent significant factor in multivariate analysis and increased concentration of cfDNA was associated with inferior 1-year survival. Moreover, cfDNA levels were found to be decreased significantly during the postoperative course when patients underwent continuous veno-venous haemofiltration. In conclusion, patients receiving livers from resuscitated donors were characterised by high postoperative cfDNA levels. Those patients showed pronounced portal hepatitis and systemic inflammatory responses in the short term leading to a high mortality. Further studies are needed to evaluate the clinical relevance of cfDNA clearance by haemoadsorption and haemofiltration in vitro and in vivo.

Background: Pleural effusions represent a common complication after liver transplantation (LT) and chest drain (CD) placement is frequently necessary. Material/Methods: In this retrospective cohort study, adult LT recipients between 2009 and 2016 were analyzed for pleural effusion formation and its treatment within the first 10 postoperative days. The aim of the study was to compare different settings of CD placement with regard to intervention-related complications. Results: Overall, 597 patients met the inclusion criteria, of which 361 patients (60.5%) received at least 1 CD within the study period. Patients with a MELD >25 were more frequently affected (75.7% versus 56.0%, P<0.001). Typically, CDs were placed in the intensive care unit (ICU) (66.8%) or in the operating room (14.1% during LT, 11.5% in the context of reoperations). In total, 97.0% of the patients received a right-sided CD, presumably caused by local irritations. Approximately one-third (35.4%) of ICU-patients required pre-interventional optimization of coagulation. Of the 361 patients receiving a CD, 15 patients (4.2%) suffered a post-interventional hemorrhage and 6 patients (1.4%) had a pneumothorax requiring further treatment. Less complications were observed when the CD was performed in the operating room compared to the ICU: 1 out 127 patients (0.8%) versus 20 out of 332 patients (6.0%); P=0.016. Conclusions: CD placement occurring in the operating room was associated with fewer complications in contrast to placement occurring in the ICU. Planned CD placement in the course of surgery might be favorable in high-risk patients.

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Non-alcoholic fatty liver disease (NAFLD) with its more progressive form non-alcoholic steatohepatitis (NASH) has become the most common chronic liver disease, thereby representing a great burden for patients and health care systems. Specific pharmacological therapies for NAFLD are still missing. Inflammation is an important driver in NASH pathogenesis, and the mechanisms underlying inflammation in NAFLD represent possible therapeutic targets. In NASH, various intra- and extrahepatic triggers involved in the metabolic injury typically lead to activation of different immune cells. This includes hepatic Kupffer cells, i.e. liver-resident macrophages, which can adopt an inflammatory phenotype and activate other immune cells by releasing inflammatory cytokines. As inflammation progresses, Kupffer cells are increasingly replaced by monocyte-derived macrophages with a distinct lipid-associated and scar-associated phenotype. Many other immune cells, including neutrophils, T lymphocytes – such as auto-aggressive cytotoxic as well as regulatory T cells – and innate lymphoid cells balance progression and regression of inflammation and subsequent fibrosis. The detailed understanding of inflammatory cell subsets and their activation pathways prompted preclinical and clinical exploration of potential targets in NAFLD/NASH. These approaches to target inflammation in NASH include inhibition of immune cell recruitment via chemokine receptors (e.g. cenicriviroc), neutralization of CD44 or galectin-3 as well as agonism to nuclear factors like peroxisome proliferator-activated receptors (PPAR) and farnesoid X receptor (FXR) that interfere with the activation of immune cells. As some of these approaches did not demonstrate convincing efficacy as monotherapies, a rational and personalized combination of therapeutic interventions may be needed for the near future.

A growing number of clinical risk scores have been proposed to predict allograft failure after liver transplantation. However, validation of currently available scores in the Eurotransplant region is still lacking. We aimed to analyze all clinically relevant donor and recipient risk scores on a large German liver transplantation data set and performed a retrospective cohort analysis of liver transplantations performed at the Charité—Universitätsmedizin Berlin from January 2007 until December 2021 with organs from donation after brain death. We analyzed 9 previously published scores in 906 liver transplantations [Eurotransplant donor risk index (ET-DRI/DRI), donor age and model for end-stage liver disease (D-MELD), balance of risk (BAR), early allograft dysfunction (EAD), model for early allograft function (MEAF), liver graft assessment following transplantation (L-GrAFT7), early allograft failure simplified estimation (EASE), and a score by Rhu and colleagues). The EASE score had the best predictive value for 3-month, 6-month, and 12-month graft survival with a c-statistic of 0.8, 0.77, and 0.78, respectively. In subgroup analyses, the EASE score was suited best for male recipients with a high-MELD (>25) and an EAD organ. Scores only based on pretransplant data performed worse compared to scores including postoperative data (eg, ET-DRI vs. EAD, p<0.001 at 3-month graft survival). Out of these, the BAR score performed best with a c-statistic of 0.6. This a comprehensive comparison of the clinical utility of risk scores after liver transplantation. The EASE score sufficiently predicted 12-month graft and patient survival. Despite a relatively complex calculation, the EASE score provides significant prognostic value for patients and health care professionals in the Eurotransplant region.