Spain is worldwide leader in deceased donation rates per million habitants and count on a strong network of twenty-five liver transplant institutions. Although the access to liver transplantation is higher than in other countries, approximately 10% of patients qualifying for liver transplantation in Spain will die in the waiting list or would be excluded due to clinical deterioration. A robust waiting list prioritization system is paramount to grant the sickest patients with the first positions in the waiting list for an earlier access to transplant. In addition, the allocation policy may not create or perpetuate inequities, particularly in a public and universal healthcare system. Hitherto, Spain lacks a unique national allocation system for elective liver transplantation. Most institutions establish their own rules for liver allocation and only two autonomous regions, namely Andalucía and Cataluña, share part of their waiting list within their territory to provide regional priority to patients requiring more urgent transplantation. This heterogeneity is further aggravated by the recently described sex-based disparities for accessing liver transplantation in Spain, and by the expansion of liver transplant indications, mainly for oncological indications, in absence of clear guidance on the optimal prioritization policy. The present document contains the recommendations from the first consensus of waiting list prioritization for liver transplantation issued by the Spanish Society of Liver Transplantation (SETH). The document was supported by all liver transplant institutions in Spain and by the Organización Nacional de Trasplantes (ONT). Its implementation will allow to homogenize practices and to improve equity and outcomes among patients with end-stage liver disease.

Background and Aims Recent advances in systemic treatments for hepatocellular carcinoma (HCC) have driven the discussion on their possible role for downstaging advanced HCC prior to liver transplantation (LT) or for bridging to LT to prevent tumor progression and reduce the dropout risk. The aim of this study was to evaluate the outcome of patients treated with TKIs before LT. Method an online survey was sent to all centers affiliated to the ELITA/ELTR network between June and December 2022. Demographic and clinical data were retrospectively collected. Results Fifty-two patients, median age 60.5 years, receiving a LT between December 2006 and September 2022 were enrolled. Thirty patients (57.6%) were treated with TKI with a downstaging purpose, while 22 (42.3%) received TKI as a bridging treatment to LT. 34 patients (65%) received sorafenib, 15 lenvatinib (28%) and 3 patients (3%) a sequential therapy with sorafenib-regorafenib. Forty-eight patients (92%) received at least one locoregional treatment before LT. Only 12 patients (23%) were in Milan criteria at treatment start time. Twenty-nine patients were Milan-in at listing (55.7%). Nine patients had neoplastic portal vein thrombosis (17.3%). The five-year survival was 70% (Figure 1). After a median time of 7.7 months (5-12.7), 7 patients (13%) experienced HCC recurrence. The only factor associated with HCC recurrence was AFP (p 0.02) at LT-We observed only a single recurrence in one of the patients with neoplastic thrombosis. Twelve patients (23%) experienced vascular or early bleeding complications after LT. The type of TKIs or the time from the last dose to LT didn't influence the risk of post-LT complications. Conclusions This is the largest collected series of patients receiving TKIs pre-LT as downstaging/bridging therapy, with a very favourable long-term outcome (70 % at 5 years) even in patients with neoplastic vein thrombosis.

Background and Aims Recent advances in systemic treatments for hepatocellular carcinoma (HCC) have driven the discussion on their possible role for downstaging advanced HCC prior to liver transplantation (LT) or for bridging to LT to prevent tumor progression and reduce the dropout risk. The aim of this study was to evaluate the outcome of patients treated with TKIs before LT. Method an online survey was sent to all centers affiliated to the ELITA/ELTR network between June and December 2022. Demographic and clinical data were retrospectively collected. Results Fifty-two patients, median age 60.5 years, receiving a LT between December 2006 and September 2022 were enrolled. Thirty patients (57.6%) were treated with TKI with a downstaging purpose, while 22 (42.3%) received TKI as a bridging treatment to LT. 34 patients (65%) received sorafenib, 15 lenvatinib (28%) and 3 patients (3%) a sequential therapy with sorafenib-regorafenib. Forty-eight patients (92%) received at least one locoregional treatment before LT. Only 12 patients (23%) were in Milan criteria at treatment start time. Twenty-nine patients were Milan-in at listing (55.7%). Nine patients had neoplastic portal vein thrombosis (17.3%). The five-year survival was 70% (Figure 1). After a median time of 7.7 months (5-12.7), 7 patients (13%) experienced HCC recurrence. The only factor associated with HCC recurrence was AFP (p 0.02) at LT-We observed only a single recurrence in one of the patients with neoplastic thrombosis. Twelve patients (23%) experienced vascular or early bleeding complications after LT. The type of TKIs or the time from the last dose to LT didn't influence the risk of post-LT complications. Conclusions This is the largest collected series of patients receiving TKIs pre-LT as downstaging/bridging therapy, with a very favourable long-term outcome (70 % at 5 years) even in patients with neoplastic vein thrombosis.

Long-term survival after liver transplantation is affected by de novo neoplasia. The incidence of this type of malignancy is increased in the setting of immunosuppressive therapy. The aim of this study was to characterize the immunologic pattern of liver transplant recipients with de novo malignancies. Fifty-one liver recipients were studied, 19 of whom had a history of de novo neoplasia. Immunophenotypic patterns among patients with/without tumors were compared. The subpopulations of CD4+ T lymphocytes and CD8+ T lymphocytes differed between the 2 types of patients studied. In patients with tumor, activation membrane markers in CD4+ T lymphocytes and CD8+ T-lymphocytes, such as CD56 or CD25, were expressed in a greater proportion, whereas activation markers CD314 and CD16 were reduced in CD56bright natural killer (NK) cells. We concluded that cytotoxic response seems to be more activated in de novo neoplasia patients, which highlights the still unknown malignancy risk effect on these immune cells.

BACKGROUND:Cytomegalovirus (CMV) is the most important viral pathogen in solid organ transplant (SOT) recipients. The role of secondary CMV prophylaxis in this population remains unclear.METHODS:Retrospective cohort study in a single center. SOT recipients treated for CMV infection from 2007 to 2014 were studied to determine the efficacy and safety of secondary prophylaxis and its impact on graft loss and mortality. The outcome variable was CMV replication in the first 3 months after the end of therapy. Secondary variables were crude mortality and graft lost censored at 5 years after transplantation. Propensity score for the use of secondary prophylaxis was used to control selection bias.RESULTS:Of the 126 treated patients, 103 (83.1%) received CMV secondary prophylaxis. CMV relapse occurred in 44 (35.5%) patients. The use of secondary prophylaxis was not associated with fewer relapses (34.0% in patients with prophylaxis vs 42.9% in those without prophylaxis, P = .29). After a mean follow-up of 32.1 months, graft loss was not different between both groups but patient mortality was significantly lower in patients who received secondary prophylaxis (5.8% vs 28.6%, P = .003).CONCLUSION:Secondary prophylaxis did not prevent CMV infection relapse but it was associated with improved patient survival.

La amiodarona se emplea en el tratamiento de arritmias ventriculares y supraventriculares. Se asocia a numerosos efectos secundarios entre los que destaca el daño hepático generalmente en forma de elevación leve y asintomática de transaminasas, aunque se han descritos casos graves. Presentamos un caso de hepatotoxicidad grave por amiodarona resuelto lentamente tras la supresión del tratamiento y en el que la biopsia hepática fue clave para el diagnóstico. Aunque no existen lesiones patognomónicas, la fosfolipidosis hepática es el hallazgo más característico.

Over the last 5 years, therapies for hepatitis C virus ( HCV ) infection have improved significantly, achieving sustained virologic response ( SVR ) rates of up to 100% in clinical trials in patients with HCV genotype 1. We investigated the effectiveness and safety of ombitasvir/paritaprevir/ritonavir±dasabuvir in an early access programme. This was a retrospective, multicentre, national study that included 291 treatment‐naïve and treatment‐experienced patients with genotype 1 or 4 HCV infection. Most patients (65.3%) were male, and the mean age was 57.5 years. The mean baseline viral load was 6.1 log, 69.8% had HCV 1b genotype, 72.9% had cirrhosis and 34.7% were treatment‐naïve. SVR at 12 weeks posttreatment was 96.2%. Four patients had virological failure (1.4%), one leading to discontinuation. There were no statistical differences in virological response according to genotype or liver fibrosis. Thirty patients experienced serious adverse events ( SAE s) (10.3%), leading to discontinuation in six cases. Hepatic decompensation was observed in five patients. Four patients died during treatment or follow‐up, three of them directly related to liver failure. Multivariate analyses showed a decreased probability of achieving SVR associated with baseline albumin, bilirubin and Child‐Pugh score B, and a greater probability of developing SAE s related to age and albumin. This combined therapy was highly effective in clinical practice with an acceptable safety profile and low rates of treatment discontinuation.

BACKGROUND There is a high prevalence of nutritional disorders in patients with liver cirrhosis (LC). This study was designed to assess the relationships between liver function, IFG-I/IGFBP-3, nutritional status, leptin, ghrelin and glucagon in 21 patients waiting for liver transplantation (LT). METHODS We studied 21 men aged 56±2.1 years who were on the LT list. They were classified according to Child-Pugh(CP) score from low to high liver dysfunction in CPA (n=4),CPB (n=11) and CPC (n=6). Body mass index (BMI) was calculated and body fat (%) was measured by air-displacement plethysmography. Resting energy expenditure (REE) and its variation over Harris-Benedict values (GER%) were assessed by indirect calorimetry. Fasting serum samples were taken to measure albumin, glucose, insulin, HbA1c, leptin, total ghrelin,glucagon, IGF-I and IGFBP3. RESULTS There were no differences in fat % and leptin values in the three groups according to CP classification. The CPC group showed higher ghrelin values than CPA and CPB(p<0.05). All groups displayed high glucagon levels and GER%values superior to 100%. Positive correlations were found between glucagon and GER% (r=0.56; p<0.01) and between glucagon and ghrelin values (r=0.66; p<0.01). IGF-I and IGFBP3 were low in all groups and showed a positive correlation with plasma albumin (r=0.52; p<0.05 and r=0.45; p<0.05 respectively). CONCLUSIONS These results show an increase in ghrelin plasma values in patients with severe liver dysfunction. Hyperglucagonemia was correlated with GER%, supporting a role of glucagon in the hypermetabolic state associated to LC,raising the possibility of becoming a therapeutic target. The measurement of IGF-I/IGFBP3 represents a good marker of liver function in patients with LC.

Background. Patients with hepatitis C virus (HCV) genotype 4 infection are poorly represented in clinical trials of 2nd-generation direct-acting antivirals (DAAs), and more data are needed to help guide treatment decisions. We still have even fewer data concerning liver transplant patients. Simeprevir (SIM) and sofosbuvir (SOF) combination is useful to treat this genotype. The aim of this study was to know the efficacy and safety of the combination SIM + SOF +/- ribavirin (RBV) in a group of liver transplant patients with HCV genotype 4 infection in Spain in real life.Methods. This was a multicenter retrospective study, including 28 HCV genotype 4 patients from 11 liver transplant centers who were treated with SIM + SOF +/- RBV. We included in the analysis demographic, clinical, and virologic data and details of serious adverse events (SAEs), including mortality rate 6 months after treatment.Results. All patients were male, mean age 52 +/- 9.43 years, and 50% were IL28B CT and 37.5% TT; 46.42% of them were pretreated and 76.9 were null responders. Fibrosis stage 4 was found in 38.7% of patients; in 67.8% of those cases the diagnosis of fibrosis was made with the use of Fibroscan, in 21.4% by liver biopsy. The average Fibroscan was 13.86 KPa. The average Model for End-Stage Liver Disease (MELD) score of cirrhotic patients was 10.9 and the Child-Pugh score was A in 70%, B in 20%, and C in 10%. We included RBV in 75% of patients, and treatment duration was 12 weeks in all patients. The sustained virologic response at week 12 (SVR12) was 95.23%. There were no discontinuations due to SAEs, but the mortality rate at 6 months after treatment was 7.14%. All deceased patients were cirrhotic, Child C, and with an average MELD score of 20.Conclusions. The combination SIM + SOF +/- RBV to treat HCV genotype 4 in liver transplant patients is an option with high rates of SVR12 and very safe, similarly to genotype 1. There was no treatment-related mortality, but when it is administered in advanced stages of fibrosis it may not be enough to prevent mortality associated with cirrhotic hepatitis C recurrence after transplantation.