Metabolic dysfunction-associated steatotic liver disease (MASLD) and its consequences represent a growing global health burden that urgently requires physiologically relevant in vitro models beyond conventional 2D culture systems. In this study, we report the successful establishment of 45 patient-derived liver organoid lines. These organoids were generated from healthy, steatotic and cirrhotic tissues collected from 207 liver surgeries at RWTH University Hospital Aachen, with an initiation success rate of 82%. The organoids were propagated for at least six passages using an optimized protocol. Multiplex immunofluorescence analysis revealed highly proliferative structures with approximately 40% Ki-67-positive cells expressing hepatocyte (Albumin and HNF4α) and cholangiocyte (CK19) markers. Intermittent LGR5 staining suggested the presence of liver progenitor cell features. Quantitative PCR results confirmed variable HNF4α expression, indicating inter-patient heterogeneity in differentiation status. Time-lapse imaging combined with mathematical modeling uncovered a biphasic growth dynamic with an initial linear expansion in the first 15 h, followed by exponential growth (doubling time ≈ 20.6 h) between 30 and 72 h. Overall, our workflow produced genetically and phenotypically stable liver organoids that recapitulate essential features of various hepatic conditions. This provides a solid foundation for disease modeling, potential drug testing, and quantitative systems biology.

Introduction: Multidisciplinary tumor boards (MTBs) are the standard for oncologic decision-making but require substantial time and personnel resources. Large language models (LLMs) may support MTBs by generating structured, guideline-based recommendations. We evaluated concordance between MTB decisions and LLM recommendations in newly diagnosed cholangiocellular adenocarcinoma (CCA) and hepatocellular carcinoma (HCC). Method: In this retrospective single-center study, MTB protocols from 2022–2023 were screened. After exclusions, 50 CCA and 50 HCC cases were analyzed. Institutional MTB recommendations were compared with outputs from ChatGPT and Claude using identical structured clinical summaries available at the time of MTB presentation. Agreement was assessed using Cohen’s kappa, and correlation using Spearman’s rank coefficient. Results: For CCA, exact concordance between MTB and ChatGPT was 80%, with substantial agreement (k = 0.688) and strong correlation (r = 0.725; both p < 0.001). Concordance with Claude was at 56%. For HCC, concordance between MTB and ChatGPT was 66%, with substantial agreement (k = 0.604) and moderate correlation (r = 0.484; both p < 0.001). Concordance with Claude was only 38%, with fair agreement (k = 0.314, p < 0.001) and weak correlation (r = 0.086, p = 0.551). Conclusions: LLM-derived recommendations varied markedly by model. ChatGPT demonstrated substantial concordance, whereas Claude showed limited agreement. MTBs appeared more individualized, while LLM outputs were more guideline-oriented. These findings highlight the potential role of LLMs as supportive tools for structured clinical reasoning and guideline adherence. Prospective multicenter studies should evaluate real-time LLM integration into MTB workflows, efficiency, decision quality, and patient outcomes safely.

Background/Objectives: The growing shortage of organs for transplantation requires optimized preservation techniques. Normothermic (NMP) and Subnormothermic Machine Perfusion (SMP) allow for the assessment of organ viability prior to transplantation and enable targeted therapeutic interventions while maintaining a metabolically active state in contrast to hypothermic settings. Methods: In this study, the synthetic perfusion solution “Omnisol” was used in a 6 h ex vivo setting with porcine kidneys (n = 6 NMP; n = 6 SMP). Perfusion parameters (arterial flow, intrarenal resistance and urinary flow), renal function (excretory and filtration performance), renal injury (cellular and circulating biomarkers) and tissue and perfusate oxygenation were assessed. Results: NMP resulted in better arterial flow and lower intrarenal resistance during the first 3 h of perfusion, while SMP surpassed NMP from 3 to 6 h. Renal injury biomarkers increased in the NMP group after 3 h, while no increase was detectable in the SMP group. Omnisol fully met the oxygen requirements of the kidneys in both groups, despite being fully synthetic. Conclusions: Both NMP and SMP offer distinct advantages for kidney preservation, and the synthetic perfusate Omnisol appears to be feasible for both methods. In this experimental setting, the data indicate that NMP of porcine kidneys was associated with favorable functional parameters during the early phase of perfusion, whereas SMP showed comparatively stable parameters at later time points. These findings should primarily be considered exploratory observations and require validation in future studies, especially for the translation into a clinical scenario using human kidneys.

Background: Postoperative liver injury remains a major challenge after curative-intended liver resection for hepatocellular carcinoma (HCC), impacting both early complications and long-term survival. The recently introduced SAAR (Sum of AST/ALT Ratios) score may serve as a novel marker for predicting postoperative outcomes. Methods: This retrospective single-center study included 213 patients undergoing liver resection for HCC between January 2007 and October 2024. The SAAR score was calculated using AST/ALT ratios on postoperative days 1 and 3 and correlated with post-hepatectomy liver failure (PHLF), disease-free survival (DFS), and overall survival (OS). The predictive performance of the SAAR score was compared with that of the combined APRI + ALBI score. Results: Patients with SAAR ≥ 2 showed significantly higher rates of PHLF (OR = 2.5, p = 0.019) and impaired long-term outcomes. Median DFS and OS were significantly reduced in the SAAR ≥ 2 group (7 vs. 24 months, p < 0.001; 12 vs. 32 months, p = 0.004, respectively). Multivariate Cox regression confirmed SAAR ≥ 2 as an independent predictor for DFS (HR = 2.1) and OS (HR = 1.9). The APRI + ALBI score also demonstrated strong preoperative predictive value for PHLF (AUC = 0.854) but not for long-term outcome.

Background: Hepatocellular carcinoma (HCC) is a leading indication for liver transplantation (LT), representing a curative treatment option for selected patients. A remaining clinical challenge is the recurrence of HCC after transplantation, impacting long-term graft and patient survival. The impact of different bridging therapies (BTs) such as transarterial chemoembolization (TACE), local ablation or liver resection on recurrence rates remains unclear. We assessed post-transplant HCC recurrence and survival focusing on the role of pre-transplant bridging therapies. Methods: Adult recipients undergoing LT for HCC at Hannover Medical School from January 2007 to September 2022 were retrospectively analyzed (n = 185). Recurrence was defined as confirmed intra or extrahepatic HCC after LT. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan–Meier estimation and log-rank testing; multivariable Cox proportional hazards regression was used to identify independent factors influencing OS. Results: Pre-transplant BT was administered in 85.4% of patients, consisting of only TACE, (n = 20; 10.8%), local ablation, (n = 32; 17.3%), liver resection (n = 27; 14.6%) or a multimodal approach (n = 50; 27%). Post-transplant HCC recurrence rate was 9.2% with a median time to recurrence of 845 days (range 126–3978 days). Patients with post-transplant HCC recurrence had a significantly higher prevalence of viral hepatitis (70.6% vs. 57.1%; p = 0.01), higher pre-transplant AFP peak levels (37.5 vs. 10 ng/mL; p = 0.03), larger tumor sizes (median 3.95 cm vs. 2.6 cm; p = 0.03) and more poorly differentiated tumors (G3; 25.0% vs. 5.3%, p = 0.04). Kaplan–Meier analysis showed significant overall differences in OS and RFS among bridging therapy groups (p = 0.03). In the subgroup of early HCC < 3 cm, local ablation was associated with significantly improved OS compared to TACE (p = 0.035). Last measured pre-transplant AFP < 15 ng/mL was a significant predictor of both improved OS (p = 0.006) and RFS (p = 0.008), whereas peak AFP did not reach significance after correction. Multivariable Cox regression revealed HCC recurrence, high recipient BMI and low LabMELD as independently associated with reduced OS after LT. Median OS after HCC recurrence was 13 months. Conclusions: Our monocentric retrospective data indicate that post-transplant HCC recurrence is uncommon but remains a challenge regarding life expectancy and is influenced by pre-transplant bridging therapy. In the subgroup of early HCC < 3 cm, local ablation was associated with significantly improved OS compared to TACE. Last measured pre-transplant AFP < 15 ng/mL was associated with both improved OS and RFS, suggesting that treatment response may also represent a prognostically relevant factor. Further prospective validation of contemporary locoregional and systemic bridging approaches, especially in the context of tumor biology and treatment response, is warranted.

Background: Cholangiocarcinoma (CCA) of the liver is a highly aggressive cancer that arises from malignant cells in the bile ducts. Radical surgery remains the only curative option, but major liver resection carries high perioperative risks. This study investigates the predictive value of preoperative bone mineral density (BMD), measured via CT, for perioperative complications, mortality, and long-term outcomes. Methods: The analysis included 202 patients who underwent curative-intent surgery for intrahepatic cholangiocarcinoma (iCCA; n = 97) or perihilar cholangiocarcinoma (pCCA; n = 105) between 2010 and 2019. Preoperative bone mineral density (BMD) was assessed using computed tomography segmentation at the level of the 12th thoracic vertebra. Osteopenia was defined according to established cutoffs. Results: Osteopenia was highly prevalent in both iCCA (53/97, 54%) and pCCA (54/105, 51%) subcohorts. Patients suffering from osteopenia were significantly older than those without (71.1 [62–76.6] years vs. 61.3 [52.9–69.2] years; p < 0.001). Alteration in BMD did not demonstrate a significant prognostic effect in terms of perioperative morbidity (Mann–Whitney U; comprehensive complication index—CCI: 34 [9–56] vs. 40 [21–72] p = 0.185; iCCA: p = 0.803; pCCA: p = 0.165). The median overall survival in our cohort was 19 [14–25] months. Patients with osteopenia did not exhibit a significantly different overall survival compared to those with normal bone mineral density (log-rank p = 0.234). Conclusions: In contrast to our previous observations in other oncological patient cohorts, osteopenia alone had no significant negative impact on clinical outcomes in our large European cohort of patients undergoing curative-intent surgery for CCA. To validate these findings, further prospective studies are warranted.