Tolerance in liver transplantation: Biomarkers and clinical relevance

Transplantation is the optimal treatment for end-stage organ failure,and modern immunosuppression has allowed important progress in short-term outcomes. However,immunosuppression poorly influences chronic rejection and elicits chronic toxicity in current clinical practice. Thus,a major goal in transplantation is to understand and induce tolerance. It is well established that human regulatory T cells expressing the transcription factor Fox P3 play important roles in the maintenance of immunological self-tolerance and immune homeostasis. The major regulatory T cell subsets and mechanisms of expansion that are critical for induction and long-term maintenance of graft tolerance and survival are being actively investigated. Likewise,other immune cells,such as dendritic cells,monocyte/macrophages or natural killer cells,have been described as part of the process known as "operational tolerance". However,translation of these results towards clinical practice needs solid tools to identify accurately and reliably patients who are going to be tolerant. In this way,a plethora of genetic and cellular biomarkers is raising and being validated worldwide in large multicenter clinical trials. Few of the studies performed so far have provided a detailed analysis of the impact of immunosuppression withdrawal on pre-existing complications derived from the long-term administration of immunosuppressive drugs and the side effects associated with them. The future of liver transplantation is aimed to develop new therapies which increase the actual low tolerant vs non-tolerant recipients ratio.

Acceptance of living liver donation among medical students: A multicenter stratified study from Spain

AIM: To analyze the attitude of Spanish medical students toward living liver donation (LLD) and to establish which factors have an influence on this attitude.METHODS: Study type: A sociological, interdisciplinary, multicenter and observational study. Study population: Medical students enrolled in Spain (n = 34000) in the university academic year 2010-2011. Sample size: A sample of 9598 students stratified by geographical area and academic year. Instrument used to measure attitude: A validated questionnaire (PCID-DVH RIOS) was self-administered and completed anonymously. Data collection procedure: Randomly selected medical schools. The questionnaire was applied to each academic year at compulsory sessions. Statistical analysis: Student´s t test, χ2 test and logistic regression analysis.RESULTS: The completion rate was 95.7% (n = 9275). 89% (n = 8258) were in favor of related LLD, and 32% (n = 2937) supported unrelated LLD. The following variables were associated with having a more favorable attitude: (1) age (P = 0.008); (2) sex (P < 0.001); (3) academic year (P < 0.001); (4) geographical area (P = 0.013); (5) believing in the possibility of needing a transplant oneself in the future (P < 0.001); (6) attitude toward deceased donation (P < 0.001); (7) attitude toward living kidney donation (P < 0.001); (8) acceptance of a donated liver segment from a family member if one were needed (P < 0.001); (9) having discussed the subject with one’s family (P < 0.001) and friends (P < 0.001); (10) a partner’s opinion about the subject (P < 0.001); (11) carrying out activities of an altruistic nature; and (12) fear of the possible mutilation of the body after donation (P < 0.001).CONCLUSION: Spanish medical students have a favorable attitude toward LLD.

Severe COVID-19 after liver transplantation, surviving the pitfalls of learning on-the-go: Three case reports

BACKGROUND The novel coronavirus 2019(COVID-19)pandemic has dramatically transformed the care of the liver transplant patient.In patients who are immunosuppressed and with multiple comorbidities,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has been associated with increased severity and mortality.The main objective of this report is to communicate our experience in the therapeutic management of SARS-CoV-2 infection in 3 liver transplant patients.Secondly,we stress the management and investigation of the contagious spreading into a liver transplant ward.CASE SUMMARY The patients were two women(aged 61 years and 62 years)and one man(aged 68 years),all of them having recently received a liver transplant.All three patients required intensive care unit admission and invasive mechanical ventilation.Two of them progressed severely until death.The other one,who received tocilizumab,had a good recovery.In the outbreak,the wife of one of the patients and four healthcare professionals involved in their care were also infected.CONCLUSION We illustrate in detail the evolution of a nosocomial COVID-19 outbreak in a liver transplant ward.We believe that these findings will contribute to a better understanding of the natural history of the disease and will improve the treatment of the liver transplant patient with COVID-19.