Objective: To map and characterize artificial intelligence (AI) applications in post-liver transplantation (LT) care, summarize comparative performance where available, and identify methodological and translational gaps. Methods: We conducted a scoping review in accordance with PRISMA-ScR. A comprehensive search of electronic databases was performed from inception through 1 April 2025. We included primary studies evaluating AI applications in the post-LT period (model development, validation, or implementation). Comparative studies were defined as those reporting head-to-head evaluation of at least two algorithmic models for the same task with quantitative performance metrics. Single-model studies were retained for evidence mapping but analyzed separately. Reviews and the other non-primary literature were included for contextual mapping. Results: The search yielded 3088 records. After deduplication, 2408 were screened, 191 full texts were assessed, and 65 studies were included. Of these, 52 reported primary outcome data. Clinical prediction studies (n = 43) focused on graft survival, rejection, fibrosis, oncologic recurrence, mortality, and composite outcomes. Operational studies (n = 3) evaluated early warning or bedside decision-support systems, and system-level studies (n = 6) examined benchmarking, donor-recipient matching, explainability, fairness, and cross-domain modeling. Most studies were retrospective and single-center, with internal validation commonly reported and external validation uncommon. Conclusions: AI research in post-LT care is expanding, with a predominant focus on clinical prediction. However, limited external validation, heterogeneous methods, and scarce real-world implementation constrain clinical readiness. Standardized evaluation and prospective integration are needed to determine whether AI tools can support decision-making and improve post-transplant outcomes.
BACKGROUND:While portal hypertension (PH) typically resolves after liver transplantation (LT), persistence of PH may affect post-transplant outcomes. We assessed the evolution of PH after LT and its impact on adverse outcomes. METHODS:We recorded clinical, laboratory, and imaging parameters of LT recipients between 2016 and 2022 in Vienna and Zagreb. Persistent features of CSPH were defined as the presence of portosystemic collaterals, platelet count (PLT) ≤ 110 G/L, and/or splenomegaly (≥ 13 cm). PH-related clinical events were defined as variceal bleeding, ascites requiring intervention, hepatic hydrothorax, portal vein thrombosis, or liver-related death within 12 months post-LT. Post-LT outcomes were analyzed using landmark Cox regression for 3 months post-LT. RESULTS:Of 645 LT recipients (76% male, median age 59 years) listed with a median MELD of 15 points and PLT of 99 G/L, features of CSPH were present in 537 (83.3%) at baseline. At year 1 after LT, MELD improved to 9 (IQR 7-12), PLT increased to 160 G/L (IQR 120-207), and features of CSPH persisted in 251/453 classifiable patients (55.4%). PH events occurred in 75 (11.6%) and 84 (13%) deaths. In a landmark analysis from 3 months post-LT (n = 521, 29 deaths), persistent thrombocytopenia (< 110 G/L) at M3 independently predicted mortality (aHR 2.31, 95% CI 1.01-5.30, p = 0.048) after adjustment for MELD, age, CRP, and pre-LT TIPS. CONCLUSIONS:While PH improves after LT, features of CSPH persisted in 55% of classifiable patients and PH-related clinical events occurred in 11.6% within the first year after LT. Persistent thrombocytopenia (< 110 G/L) at 3 months post-LT independently predicted post-LT mortality (aHR 2.31, 95% CI 1.01-5.30, p = 0.048).
Virus-associated hepatocellular carcinoma (HCC) remains a major global health burden despite effective antiviral therapies. Chronic infection with hepatitis B (HBV), hepatitis C (HCV), and hepatitis D (HDV) promotes malignant transformation through overlapping pathways of fibrosis, immune dysregulation, and microenvironmental remodeling. YKL-40, a glycoprotein secreted by hepatic stellate cells, hepatocytes under stress, macrophages, and endothelial cells, has emerged as a marker that reflects stromal activation rather than direct hepatocyte injury. Its expression is reinforced by profibrotic and angiogenic circuits, and circulating concentrations correlate with advanced fibrosis, residual risk after viral suppression, and oncologic outcomes. This review synthesizes current evidence on YKL-40 across HBV, HCV, and HDV cohorts, with emphasis on its role in bridging molecular mechanisms to clinical applications. We examine its utility in non-invasive fibrosis assessment, longitudinal monitoring after antiviral therapy, and prognostic modeling in HCC. Particular attention is given to its potential in the liver transplant pathway, where YKL-40 may refine eligibility beyond morphology, inform bridging therapy response, and predict post-transplant recurrence or graft fibrosis. Remaining challenges include its lack of disease specificity, assay variability, and limited multicenter validation. Future integration of YKL-40 into multimarker, algorithm-based frameworks could enable risk-adaptive strategies that align surveillance and transplant decisions with the evolving biology of virus-associated liver disease.
Simultaneous liver and kidney transplantation (SLKT) has been established as the treatment of choice for patients with concurrent end-stage liver and end-stage kidney diseases. The objective of this study was to analyze the outcomes of SLKT in Croatia. Databases of the Eurotransplant and Clinical Hospital Merkur from December 2007 to July 2024 were retrospectively reviewed. Patient survival was analysed by the Kaplan Meier method, while multiple logistic regression was used to assess independent association of predictors (donor and recipient age at time of SLK, pretransplant dialysis vintage and liver disease diagnosis) with patient survival. From 2007–2024, a total of 34 SLKT were performed at our institution. There were 7 female patients and 27 male patients. The median age of the patients at the time of SLKT was 57.9 (interquartile range 51.2;64) years). The indications for liver transplantation were ethylic liver cirrhosis, hyperoxaluria type 1, polycystic liver disease, primary or secondary biliary cirrhosis, hepatitis B and C cirrhosis and criptogenic liver disease. The kidney transplantation indications were end-stage renal disease of various causes, glomerulonephritis, hyperoxaluria type 1, polycystic kidney disease, diabetic nephropathy and chronic kidney disease of unknown etiology The median follow-up duration for SLKT patients was 4.1 (1.4;10.5) years. The 1-year, 5 -year and 10-year overall patient survival rates were 75.5 %, 65.4 % and 45.3 %, respectively. In a multivariate analysis only higher donor age was associated with poorer patient survival (OR 1.073 [1.006–1.145] P = 0.0325), while other variables ( recipient age, liver disease and dialysis vintage) were not independently associated with overal patient survival. Our results are in line with other major publications on SLKT patient survival. SLKT is good treatment option for selected patients with liver and end stage kidney disease.
Solid abdominal malignancies are not frequent in children, however, they present with serious challenges for all of the experts dealing with the problem, and paediatric surgeons in particular. This review deals with the surgical approaches to most frequent abdominal tumors in children – neuroblastoma, hepatoblastoma and pancreatic tumors. Different aspects in the surgical treat ment of tumors of the retroperitoneum, liver and pancreas are discussed with an emphasis on the differences in surgical approaches between children and adults.
BACKGROUND The growing disparity between the rising demand for liver transplantation (LT) and the limited availability of donor organs has prompted a greater reliance on older liver grafts. Traditionally, utilizing livers from elderly donors has been associated with outcomes inferior to those achieved with grafts from younger donors. By accounting for additional risk factors, we hypothesize that the utilization of older liver grafts has a relatively minor impact on both patient survival and graft viability. AIM To evaluate the impact of donor age on LT outcomes using multivariate analysis and comparing young and elderly donor groups. METHODS In the period from April 2013 to December 2018, 656 adult liver transplants were performed at the University Hospital Merkur. Several multivariate Cox proportional hazards models were developed to independently assess the significance of donor age. Donor age was treated as a continuous variable. The approach involved univariate and multivariate analysis, including variable selection and assessment of interactions and transformations. Additionally, to exemplify the similarity of using young and old donor liver grafts, the group of 87 recipients of elderly donor liver grafts (≥ 75 years) was compared to a group of 124 recipients of young liver grafts (≤ 45 years) from the dataset. Survival rates of the two groups were estimated using the Kaplan-Meier method and the log-rank test was used to test the differences between groups. RESULTS Using multivariate Cox analysis, we found no statistical significance in the role of donor age within the constructed models. Even when retained during the entire model development, the donor age's impact on survival remained insignificant and transformations and interactions yielded no substantial effects on survival. Consistent insignificance and low coefficient values suggest that donor age does not impact patient survival in our dataset. Notably, there was no statistical evidence that the five developed models did not adhere to the proportional hazards assumption. When comparing donor age groups, transplantation using elderly grafts showed similar early graft function, similar graft (P = 0.92), and patient survival rates (P = 0.86), and no significant difference in the incidence of postoperative complications. CONCLUSION Our center's experience indicates that donor age does not play a significant role in patient survival, with elderly livers performing comparably to younger grafts when accounting for other risk factors.
BACKGROUND Through continuous improvement in transplantation medicine, a wider range of solid organ transplant (SOT) recipients is considered suitable for complex procedures. Despite advances in modern transplantation practice, transpiring invasive fungal infections pose a substantial threat for SOT recipients. To our knowledge, cryptococcal infection confined amidst sole pancreas SOT recipients has not been described to date. Enforcement of a multidisciplinary transplant team approach in the management of pancreas SOT recipients presenting with complex cryptococcal complications is fundamental in improving patient outcomes. CASE SUMMARY We present the case of a female pancreas transplant recipient, with confirmed meningeal cryptococcosis, referred to our institution for further evaluation and treatment from the Regional Center for Infectious Diseases. On admission, the patient was weaned from the protocolized immunosuppression therapy for two consecutive weeks, in addition to tapering systemic corticosteroid remedial treatment. Our novel multidisciplinary transplant team approach embodied exhaustive discussions of possible complex and diverse multiple organ system physiologic and pathologic challenges associated with distinct management strategies in pancreas transplant recipients. Owing to the potentially devastating impact of invasive cryptococcosis in terms of morbidity and mortality, a definitive surgical intervention of pancreas transplant grafectomy was reinforced, as a pathway towards secure access to early meaningful expertise care. The patient was discharged to the Regional Center for Infectious Diseases 2 mo after the admittance further advancing to a clinical improvement. CONCLUSION The precision transplantation approach by tailoring complex medical interventions to individual needs proved indispensable in improving our patient’s outcomes.
Retroperitoneal paragangliomas are tumors of neuroectodermal origin rarely appearing in the pediatric population. We report a case of a large paraganglioma infiltrating the right kidney and inferior vena cava in a 16-year-old boy who initially presented with a right-sided varicocele. Right retroperitoneal paraganglioma was embolized preoperatively, followed by total tumor excision, right nephrectomy, inferior vena cava resection, and reconstruction using a prosthetic vascular graft. Retroperitoneal tumors requiring surgery can successfully be treated by radical resection and replacement of the inferior vena cava in experienced centers.
Background: Hepatocellular carcinoma (HCC) is one of the leading indications for liver transplantation (LT) however, selection criteria remain controversial. We aimed to identify survival factors and predictors for tumour recurrence using machine learning (ML) methods. We also compared ML models to the Cox regression model. Methods: Thirty pretransplant donor and recipient general and tumour specific parameters were analysed from 170 patients who underwent orthotopic liver transplantation for HCC between March 2013 and December 2019 at the University Hospital Merkur, Zagreb. Survival rates were calculated using the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards regression model. Data was also processed through Coxnet (a regularized Cox regression model), Random Survival Forest (RSF), Survival Support Vector Machine (SVM) and Survival Gradient Boosting models, which included pre-processing, variable selection, imputation of missing data, training and cross-validation of the models. The cross-validated concordance index (CI) was used as an evaluation metric and to determine the best performing model. Results: Kaplan-Meier curves for 5-year survival time showed survival probability of 80% for recipient survival and 82% for graft survival. The 5-year HCC recurrence was observed in 19% of patients. The best predictive accuracy was observed in the RSF model with CI of 0.72, followed by the Survival SVM model (CI 0.70). Overall ML models outperform the Cox regression model with respect to their limitations. Random Forest analysis provided several relevant outcome predictors: alpha fetoprotein (AFP), donor C-reactive protein (CRP), recipient age and neutrophil to lymphocyte ratio (NLR). Cox multivariate analysis showed similarities with RSF models in identifying detrimental variables. Some variables such as donor age and number of transarterial chemoembolization treatments (TACE) were pointed out, but these were not influential in our RSF model. Conclusions: Using ML methods in addition to classical statistical analysis, it is possible to develop sufficient prognostic models, which, compared to established risk scores, could help us quantify survival probability and make changes in organ utilization.
To determine the potential benefits and feasibility of administering maintenance therapy with dinutuximab beta for high-risk neuroblastoma (HRNB) in clinical practice, a retrospective review of charts of patients with HRNB treated at a single center in Croatia (2012–2021) was undertaken. Of 23 patients with HRNB, 11 received up to five cycles of dinutuximab beta as part of multimodal therapy; 12 patients did not (i.e., no immunotherapy). In the no immunotherapy group, one patient had complete remission (8%), and 11 patients died of tumor progression (92%). In the dinutuximab beta group, eight patients had complete remission (73%; median duration of response 5 years and 2 months), one had stable disease (9%), and two died of disease (18%). Patients who received dinutuximab beta had a higher median event-free survival (40.0 months [range: 12.5–83.0]) and median overall survival (56.0 months [range: 16.2–101.0]) than those who did not (12.9 months [range: 3.3–126.0] and 20.7 months [3.3–126.0], respectively). Dinutuximab beta was generally well tolerated; adverse events were manageable and as reported in clinical studies. These results confirm the benefits and feasibility of maintenance therapy with dinutuximab beta as part of multimodal therapy for patients with HRNB in real-world clinical practice.
Hepatitis E virus (HEV) is the most common cause of viral hepatitis globally. The first human case of autochthonous HEV infection in Croatia was reported in 2012, with the undefined zoonotic transmission of HEV genotype 3. This narrative review comprehensively addresses the current knowledge on the HEV epidemiology in humans and animals in Croatia. Published studies showed the presence of HEV antibodies in different population groups, such as chronic patients, healthcare professionals, voluntary blood donors and professionally exposed and pregnant women. The highest seroprevalence in humans was found in patients on hemodialysis in a study conducted in 2018 (27.9%). Apart from humans, different studies have confirmed the infection in pigs, wild boars and a mouse, indicating the interspecies transmission of HEV due to direct or indirect contact or as a foodborne infection. Continued periodical surveys in humans and animals are needed to identify the possible changes in the epidemiology of HEV infections.
Colorectal cancer (CRC) is among the most prevalent cancers worldwide, and its prevention and reduction of incidence is imperative. The presence of diabetes has been associated with a 30% increased risk of CRC, likely through the mechanism of hyperinsulinemia, which promotes tumorigenesis via the insulin receptor in the epithelium or by insulin-like growth factor pathways, inflammation, or adipokines, inducing cancer cell proliferation and cancer spread. Metformin, the first-line agent in treating type 2 diabetes, has a chemopreventive role in CRC development. Additionally, preclinical studies suggest synergistic effects of metformin with oxaliplatin in inhibiting in vitro models of colon cancer. Although preclinical studies on the post diagnostic use of metformin were promising and suggested its synergistic effects with chemotherapy, the data on the possible effects of metformin after surgery and other CRC treatment in the clinical setting are less conclusive, and randomized controlled trials are still lacking.
Benign liver tumors are common lesions that are usually asymptomatic and are often found incidentally due to recent advances in imaging techniques and their widespread use. Although most of these tumors can be managed conservatively or treated by surgical resection, liver transplantation (LT) is the only treatment option in selected patients. LT is usually indicated in patients that present with life-threatening complications, when the lesions are diffuse in the hepatic parenchyma or when malignant transformation cannot be ruled out. However, due to the significant postoperative morbidity of the procedure, scarcity of available donor liver grafts, and the benign course of the disease, the indications for LT are still not standardized. Hepatic adenoma and adenomatosis, hepatic hemangioma, and hepatic epithelioid hemangioendothelioma are among the most common benign liver tumors treated by LT. This article reviews the role of LT in patients with benign liver tumors. The indications for LT and long-term outcomes of LT are presented.
INTRODUCTION Croatia is a European Union (EU) member state, geographically located in south-east Europe, bordering Slovenia, Hungary, Serbia, Bosnia and Herzegovina, Montenegro, and sharing a maritime border with Italy (Figure 1). Croatia has a population of 4.1 million, with a median age of 43.1 years. The average life expectancy at birth in 2017 was 78.2 years, 3 years lower than the EU average.1 The estimated gross domestic product (GDP) per capita/y in 2018 was US $14 815.9.2 Croatia spends 6.8% of its GDP on health. The healthcare service is mostly public, and the mandatory health insurance system is complemented by voluntary insurance.1 The country’s healthcare coverage is universal, covering most medical treatments, including transplantation.FIGURE 1.: Map of Europe. Croatia (red) is located in southeast Europe, surrounded by Slovenia (Slo), Hungary (H), Serbia (S), Bosnia and Herzegovina (BiH), Montenegro (M), and sharing a maritime border with Italy (I). Croatia has been a member of Eurotransplant since 2007. Other Eurotransplant member states are presented in dark blue; the Netherlands (N), Belgium (B), Luxemburg (L), Germany (G), Austria (A), Hungary (H), and Slovenia (Slo). The map from Figure 1 has been purchased from the Stock Adobe https://stock.adobe.com.Liver Transplantation in Croatia The rapid evolution of the Croatian liver transplantation (LT) program over the last decade has been directly linked to growing deceased donor rates3 (Figure 2). Croatia has one of the highest LT rates worldwide (23–33 per million population) and has a median waiting time for LT of less than a month.3,4 This achievement is mainly due to the multidisciplinary approach and the leadership at the transplant center level along with the effective management of the deceased donation in the country and in donor hospitals.FIGURE 2.: Actual deceased donor rate (blue) and liver transplant deceased rate (red) per million population in Croatia for the period 2010–2019.3History The Croatian LT program has a 30-year history. The first LT was performed in 1990 at the University Hospital Centre Zagreb (UHCZ). However, during the Croatian War of Independence (1991–1995), all LT activities were on hold. The LT program at the Merkur University Hospital (MUH) was launched in 1998. LT in Croatia is currently performed at both institutions with the vast majority (90%) at MUH.5 The program started under challenging circumstances, burdened with the lack of donors and funding but has gradually grown based on enthusiasm of transplant professionals supported by a national transplant organization. Since 1998, over 1500 LTs have been performed at MUH, and the adult LT program has been gradually complemented with living donor, split liver, and multi-organ transplants such as liver–kidney and liver–pancreas. Today, MUH runs one of the busiest LT programs within the Eurotransplant area, as shown by its high volume activity (113 LTs performed in 2019)4 and provides educational efforts for countries in the region with low or nonexisting LT programs. The pediatric LT program was launched in 2001 at UHCZ, offering living donor, split and deceased donor transplants. The main challenge in a country of Croatia’s size is a low volume of pediatric cases with end-stage liver disease. Eurotransplant and Liver Allocation Eurotransplant is an international nonprofit organization responsible for organ allocation and cross-border sharing among 8 EU member states (Figure 1).4 Croatia joined ET in 2007, 6 years before joining the EU. For a small country like Croatia, ET membership has helped tremendously in facilitating liver allocation, especially for the country’s most critical patients. Croatia applies Model for End-Stage Liver Disease (MELD)-based liver allocation system. In addition, improved access to LT is promoted in cases where the severity of the patient’s disease is not accurately reflected by MELD scores through the system of “standard exceptions” (SE). Patients with SE status are granted a specific initial value of MELD points reassessed at 90-day intervals.6 The list of SE indications is defined nationally, whereas most SEs in Croatia are granted for hepatocellular carcinoma (HCC). An expert national audit group also grants a “nonstandard exception” status to any patient outside predefined prioritization criteria. Deceased donor livers for elective patients are primarily offered nationally and then to other ET member states according to specific allocation rules.6 Patients granted a high urgency (HU) status (eg, acute liver failure or early graft failure) are given priority at the international ET level and the allocation policy works towards providing livers for these recipients within a 48-hour time frame.7 The liver exchange balance within the ET is accomplished through the “payback” policy, where an obligation to return a liver is created for every imported HU organ. In addition, implementation of ETs allocation policy based on transparent medical criteria has contributed to the preservation of public trust in a “fair” organ allocation process. Donor Pool and Liver Utilization Rate As in most Western countries, deceased donor LT constitutes the majority of LTs in Croatia. So far, most recipients (98%) received whole deceased donor liver grafts from brain dead donors with few (2%) recipients receiving partial grafts from brain dead or living donors.4 In 2019, the utilization rate of deceased donors in Croatia had been 98% with the majority (92%) transplanted in the country.4 Utilization of extended criteria organs, especially the use of elderly livers has been one of the key strategies in the growth of Croatia’s LT program. Currently, the median age of deceased donor livers is 61 years, compared with a median of 54 years in ET.4 The acceptance of steatotic livers and livers from anti-HBc positive donors is an additional strategy in expanding the liver donor pool and increasing liver utilization rates. INDICATIONS AND OUTCOMES Cirrhosis is the main indication (64%) for LT in all adult age groups, with alcoholic liver disease being the leading etiology (62%) followed by virus-related cirrhosis (15%).8 Malignancies represent 26% of overall indications, mainly HCC (81%) with an increasing trend over the past several years.8 Hilar cholangiocarcinoma in selected patients after neoadjuvant radiotherapy is the most frequent indication for non-HCC oncologic indications (75%), followed by metastatic neuroendocrine tumors (19%).8 HU transplants represent 5.4% of LT procedures; 9.8% are retransplants.4 During the last decade, liver retransplants (re-LT) have shown a shift in indications with an increasing proportion of late re-LTs. Biliary pathology and recurrent diseases are the predominant indications, and the improved access to re-LTs has been generated primarily by the increased availability of donors.9 Since the launch of the pediatric program, 50 children (4 mo–16 y) underwent 57 LTs [segmental grafts from living donors (33%), segmental (49%), and whole (18%) grafts from deceased donors]; biliary atresia has been the leading indication (35%). Outcomes The Eurotransplant Liver Registry (ELTR) collects data from 33 countries and 174 institutions and includes >95% of European LT data.8 In Croatia, 1-year and 5-year adult patient survival rates are 83% and 70%, respectively, which is slightly lower than the ELTR data of 86% and 74%.8 Pediatric 5-year and 10-year survival rates are 64.5% and 61.1%, suggesting room for improvement. CHALLENGES AND PERSPECTIVES Our transplant activities have been recently challenged by coronavirus pandemic that has affected healthcare systems globally. In Croatia, the first coronavirus disease 2019 (COVID-19) case was confirmed on February 25, 2020, which subsequently led to temporary hold of transplant programs, with the exception of high priority liver candidates. Transplant activities reopened at the beginning of May 2020 and continued without disruption, incorporating additional molecular severe acute respiratory syndrome coronavirus-2 testing of donor and recipient before the procedure. In conclusion, Croatia has come a long way during the past 3 decades – from having an almost nonexistent LT program to being one of the leading countries when it comes to LT availability. However, much work remains to be done. The development of a national transplant registry, further expansion of the donor pool with strategies focused on living donation and donation after circulatory death, the introduction of novel technologies including machine perfusion, and finally, activities promoting access to LT in bordering countries with low volume or nonexisting transplant programs will be tackled moving forward.