Jordi Colmenero

Background and Aims: Although GEMA‐Na outperforms MELD 3.0 for liver allocation, concerns about the subjectivity of its ascites component persist. We compared the performance of a GEMA‐Na iteration that excludes ascites with other allocation scores. Approach and Results: A multinational cohort study was conducted, including adult candidates for elective liver transplantation in the UK (2010–2020), Australia (1998–2020), and Spain (2016–2021). The primary outcome was mortality or delisting for sickness within 90 days. The prognostic impact of ascites was evaluated using multivariable Cox's regression. Discrimination was assessed using Harrell's c‐statistics (Hc). The study included 15 391 patients (28.5% women). The prevalence of the primary outcome was 5.8% in the UK, 5.3% in Australia, and 4.7% in Spain. The presence and severity of ascites was associated with an incremental risk of the primary outcome: 3.3% without ascites, 5.8% with mild ascites, and 7.7% with moderate–severe ascites ( p < 0.001). Removal of ascites from the GEMA‐Na score resulted in a one‐point reduction in 18% of patients (52.4% of patients with moderate–severe ascites). GEMA‐Na without ascites showed only a marginal decrease in discrimination (Hc = 0.755 vs. Hc = 0.753; p = 0.007) but still significantly outperformed MELD 3.0 (Hc = 0.734; p < 0.001) and MELD‐Na (Hc = 0.737; p < 0.001). In women, GEMA‐Na with and without ascites demonstrated comparable discrimination (Hc = 0.784 vs. Hc = 0.783; p = 0.61), both outperforming MELD 3.0 (Hc = 0.750; p < 0.001), and MELD‐Na (Hc = 0.749; p < 0.001). Conclusions: Despite the prognostic impact of ascites among liver transplant candidates, GEMA‐Na without ascites outperformed other scores in predicting wait‐list outcomes and may be used wherever the inclusion of ascites is considered too subjective.

The use of biomarkers in liver transplantation (LT) may be useful for the noninvasive assessment of T-cell-mediated rejection (TCMR). This study aimed to: (1) determine if changes in circulating microRNAs (miRNAs) in rejector patients reflect those at the tissue level; (2) assess a biomarker score (including miRNAs 155-5p, 181a-5p, and CXCL-10) in an independent cohort and (3) evaluate the score’s utility in detecting other LT-related complications. A prospective cohort of 151 LT recipients was followed during the first year after surgery. Patients with abnormal liver function tests (LFTs) underwent liver biopsy (LB) to rule out TCMR. Plasma samples were collected at predefined time points to analyse miRNAs and chemokines and their ability to predict and diagnose TCMR. To correlate plasma biomarkers with their tissue expression, 27 liver tissue samples (9 with normal LFTs and 18 with TCMR) were selected. Forty patients were diagnosed with TCMR. Circulating miRNAs (155-5p and 122-5p) reflected tissue-level changes in TCMR (p < 0.001, 3.3-fold increase for miR-155 and 2.3 for miR-122). Additionally assessed plasma miRNA 885-5p and chemokines CXCL-9 and CXCL-11, were also significantly elevated in TCMR but did not improve the performance of our previously biomarker score for TCMR (AUROC 0.94 for prediction, 0.99 for diagnosis). In conclusion, we confirmed in an independent cohort the performance of the score based on miR-155-5p, miR-181a-5p, and CXCL10. The correlation between circulating miRNAs and liver tissue expression underscores their value for predicting and diagnosing TCMR.

Background & Aims: Liver transplantation (LT) remains the only cure for severe polycystic liver disease (PLD). However, LT indications and strategies vary across Europe, resulting in (unwanted) practice variation and unequal access to care for patients with PLD. This study aimed to (1) identify existing PLD-specific LT criteria across European countries, (2) assess which criteria are considered relevant by specialist, and (3) map the variation in liver-kidney transplant strategies among patients with autosomal dominant polycystic kidney disease (ADPKD). Methods: National PLD-specific LT criteria were collected, and if unavailable ERN RARE-Liver representatives from that country were asked to provide information. An online survey was conducted amongst hepatologists, LT surgeons, and nephrologists managing patients with PLD. The survey assessed relevant LT indications/listing requirements, clinical case evaluations, and explored preferences for liver-kidney transplantation in patients with ADPKD. Results: Defined LT criteria for patients with PLD were available in only 8 of the 17 assessed countries and showed substantial variation. Sixty-nine clinicians (43 hepatologists, 15 surgeons, 11 nephrologists), predominantly from LT centers (75.4%), completed the survey. Key LT indications were recurrent liver cyst infections (78.3%), significant impaired quality of life (75.4%), and severe malnutrition (75.4%). In ADPKD simultaneous liver-kidney transplantation (SLK) was preferred by 40.4% of respondents, primarily due the favorable immunological profile (47.6%) and prevention of renal failure (33.3%). In contrast, those favoring a liver-first approach (30.8%), followed by sequential kidney transplant, highlighted the potential harm to the kidney graft during SLK (62.5%). Conclusions: Uniform PLD-specific LT criteria in Europe are lacking. While recurrent liver cyst infections, decreased quality of life, and malnutrition are widely recognized as crucial LT indications, they are insufficiently reflected in existing criteria, contributing to unequal access to LT. Moreover, considerable variation exists in liver-kidney transplantation for ADPKD patients, with a current lack of evidence to support one approach over another.

Background and Aims: Despite liver transplantation (LT) is considered the optimal treatment for hepatocellular carcinoma (HCC), particularly in patients with impaired liver function, the shortage of donors has forced the application of very restrictive criteria for selecting ideal candidates for whom LT can offer the best outcome. With the evolving LT landscape due to the advent of direct‐acting antivirals (DAAs) and the steady increase in donors, major efforts have been made to expand the transplant eligibility criteria for HCC. In addition, the emergence of immune checkpoint inhibitors (ICIs) for the treatment of HCC, with demonstrated efficacy in earlier stages, has revolutionized the therapeutic approach for these patients, and their integration in the setting of LT is challenging. Management of immunological compromise from ICIs, including the wash‐out period before LT and post‐LT immunosuppression adjustments, is crucial to balance the risk of graft rejection against HCC recurrence. Additionally, the effects of increased immunosuppression on non‐hepatic complications must be understood to prevent them from becoming obstacles to long‐term OS. Methods and Results: In this review, we will evaluate the emerging evidence and its implications for the future of LT in HCC. Addressing these novel challenges and opportunities, while integrating the current clinical evidence with predictive algorithms, would ensure a fair balance between individual patient needs and the overall population benefit in the LT system.

Liver transplantation (LT) remains one of the most effective treatments for hepatocellular carcinoma (HCC) and significantly enhances patient survival. However, the application of LT for HCC faces challenges owing to advancements in cancer-specific treatment modalities and the increased burden of patients’ comorbidities. This narrative review explores current controversies and advancements in LT for HCC. Key areas of focus include the management of comorbidities and patient education by advanced practice nurses, impacts of frailty on waitlists and post-LT outcomes, selection criteria for LT in the era of new downstaging tools, role of radiology in patient selection, and implications of potential immunotherapy use both before and after LT. Additionally, the importance of immunosuppression management with strategies aimed at minimizing rejection while considering the risk of HCC recurrence and the role of surveillance for HCC recurrence is highlighted. This review also underscores the importance of a multidisciplinary approach for optimizing outcomes in patients with HCC undergoing LT.

Background/Objectives: Liver Transplantation (LT) is the second most common solid organ transplantation. Medication adherence on LT patients is key to avoiding graft failure, mortality, and important quality of life losses. The aim of this study is to identify risk-factors for non-adherence to treatment of liver transplant patients according to reliable published evidence. Methods: An umbrella review within the context of adherence to immunosuppressant medication of LT patients, was conducted. The review was performed in accordance with the principles of the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Results: A total of 11 articles were finally included for the review. Non-adherence factors were identified and allocated using the WHO classification of factors for non-adherence. Each of these groups contains a subset of factors that have been shown to influence adherence to medication, directly or indirectly, according to literature findings. Conclusions: The results of the review indicate that sociodemographic factors, factors related to the patient, factors related to the treatment, condition-related and health system-related factors are good categories of predictors for both adherence and non-adherence to immunosuppressive medication in LT patients. This list of factors may help physicians in the treating and recognizing of patients with a potential risk of non-adherence and it could help in the designing of new tools to better understand non-adherence after LT and targeted interventions to promote adherence of LT patients.