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Liver transplantation is the most effective treatment for end-stage liver disease. Transplant indications have been progressively increasing, with a huge discrepancy between the supply and demand of optimal organs. In this context, the use of extended criteria donor grafts has gained importance, even though these grafts are more susceptible to ischemic reperfusion injury (IRI). Hepatic IRI is an inherent and inevitable consequence of all liver transplants; it involves ischemia-mediated cellular damage exacerbated upon reperfusion and its severity directly affects graft function and post-transplant complications. Strategies for organ preservation have been constantly improving since they first emerged. The current gold standard for preservation is perfusion solutions and static cold storage. However, novel approaches that allow extended preservation times, organ evaluation, and their treatment, which could increase the number of viable organs for transplantation, are currently under investigation. This review discusses the mechanisms associated with IRI, describes existing strategies for liver preservation, and emphasizes novel developments and challenges for effective organ preservation and optimization.

To the editor,Diagnosis of sinusoidal obstruction syndrome (SOS) after hematopoietic cell transplantation (HCT) is based on clinical criteria including weight gain, ascites, he-patomegaly, and jaundice.[1] However, clinical and histological features and prognosis of SOS after liver transplantation (LT) seem to differ from SOS after H CT.[2,3] We aimed to determine the characteristics and outcomes of SOS after LT.

Cancer is the leading cause of death after liver transplantation (LT). This multicenter case–control nested study aimed to evaluate the effect of maintenance immunosuppres sion on post-LT malignancy. The eligible cohort included 2495 LT patacrolimus-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 < .001), male sex (HR = 1.50 [95% CI 1.14–1.99]), smoking habit (HR = 1.96 [95% CI 1.42–2.66]), and alcoholic liver disease (HR = 1.53 [95% CI 1.19–1.97]). In selected cases and controls (n = 850), the immunosuppression protocol was similar (p = .51). An increased cumulative exposure to tacrolimus (CET), calculated by the area under curve of trough concentrations, was the only immunosuppression-related predictor of post-LT malignancy after controlling for clinical features and baseline HCC (CET at 3 months p = .001 and CET at 12 months p = .004). This effect was consistent for de novo malignancy (after excluding HCC recurrence) and for internal neoplasms (after excluding non-melanoma skin cancer). Therefore, tacrolimus minimization, as monitored by CET, is the key to modulate immunosuppression in order to prevent cancer after LT.

Cancer is the leading cause of death after liver transplantation (LT). This multicenter case–control nested study aimed to evaluate the effect of maintenance immunosuppres sion on post-LT malignancy. The eligible cohort included 2495 LT patacrolimus-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 < .001), male sex (HR = 1.50 [95% CI 1.14–1.99]), smoking habit (HR = 1.96 [95% CI 1.42–2.66]), and alcoholic liver disease (HR = 1.53 [95% CI 1.19–1.97]). In selected cases and controls (n = 850), the immunosuppression protocol was similar (p = .51). An increased cumulative exposure to tacrolimus (CET), calculated by the area under curve of trough concentrations, was the only immunosuppression-related predictor of post-LT malignancy after controlling for clinical features and baseline HCC (CET at 3 months p = .001 and CET at 12 months p = .004). This effect was consistent for de novo malignancy (after excluding HCC recurrence) and for internal neoplasms (after excluding non-melanoma skin cancer). Therefore, tacrolimus minimization, as monitored by CET, is the key to modulate immunosuppression in order to prevent cancer after LT.

To the editor,Diagnosis of sinusoidal obstruction syndrome (SOS) after hematopoietic cell transplantation (HCT) is based on clinical criteria including weight gain, ascites, he-patomegaly, and jaundice.[1] However, clinical and histological features and prognosis of SOS after liver transplantation (LT) seem to differ from SOS after H CT.[2,3] We aimed to determine the characteristics and outcomes of SOS after LT.

To the editor,Diagnosis of sinusoidal obstruction syndrome (SOS) after hematopoietic cell transplantation (HCT) is based on clinical criteria including weight gain, ascites, he-patomegaly, and jaundice.[1] However, clinical and histological features and prognosis of SOS after liver transplantation (LT) seem to differ from SOS after H CT.[2,3] We aimed to determine the characteristics and outcomes of SOS after LT.

Cancer is the leading cause of death after liver transplantation (LT). This multicenter case–control nested study aimed to evaluate the effect of maintenance immunosuppres sion on post-LT malignancy. The eligible cohort included 2495 LT patacrolimus-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 < .001), male sex (HR = 1.50 [95% CI 1.14–1.99]), smoking habit (HR = 1.96 [95% CI 1.42–2.66]), and alcoholic liver disease (HR = 1.53 [95% CI 1.19–1.97]). In selected cases and controls (n = 850), the immunosuppression protocol was similar (p = .51). An increased cumulative exposure to tacrolimus (CET), calculated by the area under curve of trough concentrations, was the only immunosuppression-related predictor of post-LT malignancy after controlling for clinical features and baseline HCC (CET at 3 months p = .001 and CET at 12 months p = .004). This effect was consistent for de novo malignancy (after excluding HCC recurrence) and for internal neoplasms (after excluding non-melanoma skin cancer). Therefore, tacrolimus minimization, as monitored by CET, is the key to modulate immunosuppression in order to prevent cancer after LT.

The number of patients awaiting liver transplantation (LT) in Spain has halved from 2015 to 2019 due to the reduction of candidates with hepatitis C and the successful implementation of nonheart beating donation programs across the country. The Spanish Society for Liver Transplantation has committed to take advantage of this situation by developing consensus around potential areas to expand the current indications for LT. The consensus group was composed of 6 coordinators and 23 expert delegates, each one representing an LT institution in Spain. Methods. A modified Delphi approach was used to identify areas to expand indications for LT and to build consensus around paramount aspects, such as inclusion criteria and waitlist prioritization within each area. The scientific evidence and strength of recommendations were assessed by the “Grading of Recommendations Assessment, Development, and Evaluation” system. Results. The consensus process resulted in the identification of 7 potential areas to expand criteria in LT: recipient’s age, hepatocellular carcinoma, alcoholic hepatitis, acute-on-chronic liver failure, hilar and intrahepatic cholangiocarcinoma, and unresectable liver metastases of colorectal cancer. Conclusions. We present the main recommendations issued for each topic, together with their core supporting evidence. These recommendations may allow for expanding criteria for LT homogenously in Spain and may provide a guidance to other countries/institutions facing a similar scenario.

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.

The number of patients awaiting liver transplantation (LT) in Spain has halved from 2015 to 2019 due to the reduction of candidates with hepatitis C and the successful implementation of nonheart beating donation programs across the country. The Spanish Society for Liver Transplantation has committed to take advantage of this situation by developing consensus around potential areas to expand the current indications for LT. The consensus group was composed of 6 coordinators and 23 expert delegates, each one representing an LT institution in Spain. Methods. A modified Delphi approach was used to identify areas to expand indications for LT and to build consensus around paramount aspects, such as inclusion criteria and waitlist prioritization within each area. The scientific evidence and strength of recommendations were assessed by the “Grading of Recommendations Assessment, Development, and Evaluation” system. Results. The consensus process resulted in the identification of 7 potential areas to expand criteria in LT: recipient’s age, hepatocellular carcinoma, alcoholic hepatitis, acute-on-chronic liver failure, hilar and intrahepatic cholangiocarcinoma, and unresectable liver metastases of colorectal cancer. Conclusions. We present the main recommendations issued for each topic, together with their core supporting evidence. These recommendations may allow for expanding criteria for LT homogenously in Spain and may provide a guidance to other countries/institutions facing a similar scenario.

The number of patients awaiting liver transplantation (LT) in Spain has halved from 2015 to 2019 due to the reduction of candidates with hepatitis C and the successful implementation of nonheart beating donation programs across the country. The Spanish Society for Liver Transplantation has committed to take advantage of this situation by developing consensus around potential areas to expand the current indications for LT. The consensus group was composed of 6 coordinators and 23 expert delegates, each one representing an LT institution in Spain. Methods. A modified Delphi approach was used to identify areas to expand indications for LT and to build consensus around paramount aspects, such as inclusion criteria and waitlist prioritization within each area. The scientific evidence and strength of recommendations were assessed by the “Grading of Recommendations Assessment, Development, and Evaluation” system. Results. The consensus process resulted in the identification of 7 potential areas to expand criteria in LT: recipient’s age, hepatocellular carcinoma, alcoholic hepatitis, acute-on-chronic liver failure, hilar and intrahepatic cholangiocarcinoma, and unresectable liver metastases of colorectal cancer. Conclusions. We present the main recommendations issued for each topic, together with their core supporting evidence. These recommendations may allow for expanding criteria for LT homogenously in Spain and may provide a guidance to other countries/institutions facing a similar scenario.

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 1 and June 27, 2020, 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 of 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 percent 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.

Recurrent attacks of acute intermittent porphyria (AIP) result in poor quality of life and significant risks of morbidity and mortality. Liver transplantation (LT) offers a cure, but published data on outcomes after LT are limited. We assessed the pretransplant characteristics, complications, and outcomes for patients with AIP who received a transplant. Data were collected retrospectively from the European Liver Transplant Registry and from questionnaires sent to identified transplant and porphyria centers. We studied 38 patients who received transplants in 12 countries from 2002 to 2019. Median age at LT was 37 years (range, 18-58), and 34 (89%) of the patients were women. A total of 9 patients died during follow-up, and 2 patients were retransplanted. The 1-year and 5-year overall survival rates were 92% and 82%, which are comparable with other metabolic diseases transplanted during the same period. Advanced pretransplant neurological impairment was associated with increased mortality. The 5-year survival rate was 94% among 19 patients with moderate or no neuropathy at LT and 83% among 10 patients with severe neuropathy (P = 0.04). Pretransplant renal impairment was common. A total of 19 (51%) patients had a GFR < 60 mL/minute. Although few patients improved their renal function after LT, neurological impairments improved, and no worsening of neurological symptoms was recorded. No patient had AIP attacks after LT, except for a patient who received an auxiliary graft. LT is a curative treatment option for patients with recurrent attacks of AIP. Severe neuropathy and impaired renal function are common and increase the risk for poor outcomes. If other treatment options fail, an evaluation for LT should be performed early.

Livers from donation after circulatory death (DCD) donors are an increasingly more common source of organs for transplantation. While there are few high-level studies in the field of DCD liver transplantation, clinical practice has undergone progressive changes during the past decade, in particular due to mounting use of postmortem normothermic regional perfusion (NRP). In Spain, uncontrolled DCD has been performed since the late 1980s/early 1990s, while controlled DCD was implemented nationally in 2012. Since 2012, the rise in DCD liver transplant activity in Spain has been considerable, and the great majority of DCD livers transplanted in Spain today are recovered with NRP. A panel of the Spanish Liver Transplantation Society was convened in 2018 to evaluate current evidence and accumulated experience in DCD liver transplantation, in particular addressing issues related to DCD liver evaluation, acceptance criteria, and recovery as well as recipient selection and postoperative management. This panel has created a series of consensus statements for the standard of practice in Spain and has published these statements with the hope they might help guide other groups interested in implementing new forms of DCD liver transplantation and/or introducing NRP into their clinical practices.

Livers from donation after circulatory death (DCD) donors are an increasingly more common source of organs for transplantation. While there are few high-level studies in the field of DCD liver transplantation, clinical practice has undergone progressive changes during the past decade, in particular due to mounting use of postmortem normothermic regional perfusion (NRP). In Spain, uncontrolled DCD has been performed since the late 1980s/early 1990s, while controlled DCD was implemented nationally in 2012. Since 2012, the rise in DCD liver transplant activity in Spain has been considerable, and the great majority of DCD livers transplanted in Spain today are recovered with NRP. A panel of the Spanish Liver Transplantation Society was convened in 2018 to evaluate current evidence and accumulated experience in DCD liver transplantation, in particular addressing issues related to DCD liver evaluation, acceptance criteria, and recovery as well as recipient selection and postoperative management. This panel has created a series of consensus statements for the standard of practice in Spain and has published these statements with the hope they might help guide other groups interested in implementing new forms of DCD liver transplantation and/or introducing NRP into their clinical practices.

Livers from donation after circulatory death (DCD) donors are an increasingly more common source of organs for transplantation. While there are few high-level studies in the field of DCD liver transplantation, clinical practice has undergone progressive changes during the past decade, in particular due to mounting use of postmortem normothermic regional perfusion (NRP). In Spain, uncontrolled DCD has been performed since the late 1980s/early 1990s, while controlled DCD was implemented nationally in 2012. Since 2012, the rise in DCD liver transplant activity in Spain has been considerable, and the great majority of DCD livers transplanted in Spain today are recovered with NRP. A panel of the Spanish Liver Transplantation Society was convened in 2018 to evaluate current evidence and accumulated experience in DCD liver transplantation, in particular addressing issues related to DCD liver evaluation, acceptance criteria, and recovery as well as recipient selection and postoperative management. This panel has created a series of consensus statements for the standard of practice in Spain and has published these statements with the hope they might help guide other groups interested in implementing new forms of DCD liver transplantation and/or introducing NRP into their clinical practices.