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De novo malignancies (DNMs) following liver transplantation (LT) have been reported as 1 of the major causes of late mortality, being the most common cause of death in the second decade after LT. The overall incidence of DNMs is reported to be in the range of 3.1% to 14.4%, and the incidence is 2- to 3-fold higher in transplant recipients than in age- and sex-matched healthy controls. Long-term immunosuppressive therapy, which is the key in maintaining host tolerance and achieving good long-term outcomes, is known to contribute to a higher risk of DNMs. However, the incidence and type of DNM also depends on different risk factors, including patient demographics, cause of the underlying chronic liver disease, behavior (smoking and alcohol abuse), and pre-existing premalignant conditions. The estimated standardized incidence ratio for different DNMs is also variable. The International Liver Transplantation Society-Spanish Society of Liver Transplantation Consensus Conference working group on DNM has summarized and discussed the current available literature on epidemiology, risk factors, management, and survival after DNMs. Recommendations for screening and surveillance for specific tumors, as well as immunosuppression and cancer-specific management in patients with DNM, are summarized.

Cancer is the leading cause of death after liver transplantation (LT). This multicenter case-control nested study aimed to evaluate the effect of maintenance immunosuppression on post-LT malignancy. The eligible cohort included 2,495 LT patients who received tacrolimus-based immunosuppression. After 13,922 person/years follow-up, 425 patients (19.7%) developed malignancy (cases) and were matched with 425 controls by propensity score based on age, gender, smoking habit, etiology of liver disease and hepatocellular carcinoma (HCC) before LT. The independent predictors of post-LT malignancy were older age (HR=1.06 [95%CI 1.05-1.07]; p

Anticoagulation and antiplatelet therapies are increasingly used in liver transplant (LT) candidates and recipients due to cardiovascular comorbidities, portal vein thrombosis, or to manage posttransplant complications. The implementation of the new direct-acting oral anticoagulants and the recently developed antiplatelet drugs is a great challenge for transplant teams worldwide, as their activity must be monitored and their complications managed, in the absence of robust scientific evidence. In this changing and clinically heterogeneous scenario, the Spanish Society of Liver Transplantation and the Spanish Society of Thrombosis and Haemostasis aimed to achieve consensus regarding the indications, drugs, dosing, and timing of anticoagulation and antiplatelet therapies initiated from the inclusion of the patient on the waiting list to post-LT surveillance. A multidisciplinary group of experts composed by transplant hepatologists, surgeons, hematologists, transplant-specialized anesthesiologists, and intensivists performed a comprehensive review of the literature and identified 21 clinically relevant questions using the patient-intervention-comparison-outcome format. A preliminary list of recommendations was drafted and further validated using a modified Delphi approach by a panel of 24 transplant delegates, each representing a LT institution in Spain. The present consensus statement contains the key recommendations together with the core supporting scientific evidence, which will provide guidance for improved and more homogeneous clinical decision making.

BACKGROUND AND AIMS: Despite concerns that liver transplant (LT) recipients may be at increased risk of unfavorable outcomes from COVID-19 due the high prevalence of co-morbidities, immunosuppression and ageing, a detailed analysis of their effects in large studies is lacking. METHODS: Data from adult LT recipients with laboratory confirmed SARS-CoV2 infection were collected across Europe. All consecutive patients with symptoms were included in the analysis. RESULTS: Between March 1st and June 27th2020, data from 243 adult symptomatic cases from 36 centers and 9 countries were collected. Thirty-nine (16%) were managed as outpatients while 204 (84%) required hospitalization including admission to the ICU (39/204, 19.1%). Forty-nine (20.2%) patients died after a median of 13.5 (10-23) days, respiratory failure was the major cause. After multivariable Cox regression analysis, age >70 (HR, 4.16; 95% CI, 1.78-9.73) had a negative effect and tacrolimus (TAC) use (HR, 0.55; 95% CI, 0.31-0.99) had a positive independent effect on survival. The role of co-morbidities was strongly influenced by the dominant effect of age where comorbidities increased with the increasing age of the recipients. In a second model excluding age, both diabetes (HR, 1.95; 95% CI, 1.06-3.58) and chronic kidney disease (HR, 1.97; 95% CI, 1.05-3.67) emerged as associated with death CONCLUSIONS: Twenty-five per cent of patients requiring hospitalization for Covid-19 died, the risk being higher in patients older than 70 and with medical co-morbidities, such as impaired renal function and diabetes. Conversely, the use of TAC was associated with a better survival thus encouraging clinicians to keep TAC at the usual dose.

Background: COVID-19 is a disease caused by SARS-CoV-2, which can develop into a hyper-inflammatory late phase or “cytokine storm” that poses high risk of death. It has been proposed that the management of this cytokine storm is crucial to increase the survival rate of COVID-19 patients. However, to date there are no diagnostic criteria based on inflammatory markers that could be used to select the COVID-19 patients at risk of developing a cytokine storm or effective interventions that can decreased mortality in these patients. Methods: We carried out a quasi-experimental study to test whether high dose corticosteroid pulse therapy with either dexametaxona or methylprednisolone were associated with reduced mortality in patients at risk of cytokine storm and assess which laboratory markers can be used to pre-select these patients. To control the development and progression of this hyper-inflammtory phase, 64 patients (20.1%) were treated with high dose corticosteroid pulse therapy (HDCPT) by using either dexametaxona or methylprednisolone daily for 2-5 days at doses of at least 30mg or 125mg respectively. To determine diagnostic criteria that can be used to defined patients at risk of cytokine storm, we carried out a 30-day time course analysis of laboratory markers between survivors and non-survivors. A multivariate Cox regression (controlling for co-morbidities and therapies) was carried out to determine whether HDCPT (among other interventions) was associated with decreased mortality in both the full cohort, and in a subgroup containing the patients with the derived criteria. Findings: Out of 500 patients originally recruited, 381 met the inclusion criteria of SARS-COV-19 detection by PCR or serology (n=272, 71.2%) or high clinical suspicion (n= 46, 16.9 %), defined as having bilateral pulmonary infiltrate or lymphopenia with according clinical profile. HDCPT was the only intervention that showed a significant decrease in mortality (odds ratio = 0.093 [95% CI 0.023 – 0.38]; P = 40 pg/ml and/or two of the following: C-reactive protein >= 100 mg/L, D-dimer >= 1000 ng/ml, ferritin >= 500 ng/ml and lactate dehydrogenase >= 300 U/L. Multivariate Cox regression by pre-selecting the patients using this criteria evidenced also a decreased mortality rate with HDCPT with a lower odds ratio (odds ratio = 0.081 [95% CI 0.011 – 0.56]; P = 0.011). Conclusions: Preventing and/or controlling the development of the cytokine storm in patients at high-inflammatory risk with HDCPT is a widely available therapy to increase survival rate in these patients. We estimate a 14.2% [95% CI 0.792 - 0.975] increase of survival rate. We also suggest some initial clinical variables that can aid with the identification of the patients who will benefit from this intervention. Funding Statement: There were no funding sources in this study. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the Ethics Committee of the Complejo Hospitalario de Jaen (Hospital of Jaen), Spain (0946-N-20). According to the local ethics committee regulations, verbal consent was obtained from all the patients that joined the study.

Despite unique immunoregulatory properties pointing toward tolerance, the liver allograft can be negatively impacted by humoral alloreactivity, with immediate as well as long-term harmful consequences. With regard to the unmet need of long-term outcomes improvement after liver transplantation, donor-specific antibodies have recently been the matter of intense study in this context. We review here recent advances regarding the understanding of the impact of preformed as well as de novo anti-human leukocyte antigen donor-specific antibodies in liver transplantation and discuss potential strategies to overcome this problem.