Background and Aims ReMELD-Na and MELD 3.0 are newly introduced prognostic scores for liver graft allocation, but their ability to predict the outcome after transjugular intrahepatic portosystemic shunt (TIPS) for refractory ascites in Western populations remains uncertain. This study compared the prognostic performance of ReMELD-Na and MELD 3.0 with FIPS, MELD-Na, MELD. Methods In this multicenter retrospective study, 1,621 cirrhotic patients undergoing TIPS for refractory ascites at eight German centers (January 2004-June 2024) were analyzed. The outcome was the event of either death or LTx within 90 days (primary) and one year (secondary) after TIPS. Prognostic performance was evaluated using receiver operator characteristic (ROC) and area under the curve (AUC), including sex-stratified analyses, and compared using DeLong’s test. High-risk groups (above the 85th/75th for the 90- day and one-year endpoint, respectively) were compared to non-high-risk groups using Kaplan-Meier analysis, scatter plots and descriptive score-vs-score spline smooth analysis. Results All scores showed limited predictive performance, with ROC-AUC values of 0.635 to 0.675 for the 90-day and 0.644 to 0.672 for the one-year outcome. Female patients demonstrated higher ROC-AUC values, reaching 0.714 for FIPS at 90 days. ReMELD-Na showed significantly lower ROC-AUC values than FIPS, MELD 3.0, and MELD-Na. Beyond this, MELD 3.0´s ROC-AUC values were comparable to those of the other scores. All models identified high-risk groups with increased event rates of death and LTx. Conclusions After TIPS for refractory ascites, all scores exhibited limited prognostic performance, but adequately distinguished high- and low-risk patients. MELD 3.0 performed comparably to established models, while ReMELD-Na was inferior to FIPS, MELD 3.0, and MELD-Na. Higher ROC-AUCs in women indicate sex-specific differences and the need for sex-sensitive prognostic tools. IMPACT AND IMPLICATIONS Accurate prediction of post-TIPS outcomes is essential to optimize management strategies for patients with cirrhosis and refractory ascites. In this large multicenter study, MELD 3.0 demonstrated prognostic performance comparable to established models, whereas ReMELD-Na - recently implemented for liver allocation in the Eurotransplant region - showed inferior predictive performance, raising concerns about its applicability in this setting. These results are particularly relevant as existing models may inadequately capture post-TIPS risk, especially in male patients. Collectively, the findings advocate for a cautious application of ReMELD-Na in clinical decision-making and emphasize the need to develop sex-sensitive, multidimensional prognostic tools to improve patient selection and surveillance.

BACKGROUND & AIMS:ReMELD-Na and MELD 3.0 are newly introduced prognostic scores for liver graft allocation, but their ability to predict outcomes after transjugular intrahepatic portosystemic shunt (TIPS) for refractory ascites in Western populations remains uncertain. This study compared the prognostic performance of ReMELD-Na and MELD 3.0 with FIPS, MELD-Na, and MELD. METHODS:In this multicenter retrospective study, 1,621 patients with cirrhosis undergoing TIPS for refractory ascites at eight German centers (January 2004-June 2024) were analyzed. Outcomes were the composite of death or liver transplantation (LTx) within 90 days (primary endpoint) and one year (secondary endpoint) after TIPS. Prognostic performance was evaluated using the area under the receiver-operating characteristic curve (AUROC), including sex-stratified analyses, and compared using DeLong's test. High-risk groups (above the 85th percentile for the 90-day endpoint and the 75th percentile for the 1-year endpoint) were compared with non-high-risk groups using Kaplan-Meier analysis, scatter plots, and descriptive score-vs.-score spline smoothing. RESULTS:All scores showed limited predictive performance, with AUROC values ranging from 0.635 to 0.675 for the 90-day outcome and from 0.644 to 0.672 for the 1-year outcome. Female patients demonstrated higher AUROC values, reaching 0.714 for FIPS at 90 days. ReMELD-Na showed significantly lower AUROC values than FIPS, MELD 3.0, and MELD-Na. In contrast, MELD 3.0 demonstrated AUROC values comparable to those of the other scores. All models identified high-risk groups with increased rates of death and LTx. CONCLUSIONS:After TIPS for refractory ascites, all scores exhibited limited prognostic performance, but adequately distinguished high- and low-risk patients. MELD 3.0 performed comparably to established models, while ReMELD-Na was inferior to FIPS, MELD 3.0, and MELD-Na. Higher AUROC values in women suggest sex-specific differences and highlight the need for sex-sensitive prognostic tools. IMPACT AND IMPLICATIONS:Accurate prediction of post-TIPS outcomes is essential to optimize management strategies for patients with cirrhosis and refractory ascites. In this large multicenter study, MELD 3.0 demonstrated prognostic performance comparable to established models, whereas ReMELD-Na - recently implemented for liver allocation in the Eurotransplant region - showed inferior predictive performance, raising concerns about its applicability in this setting. These results are particularly relevant as existing models may inadequately capture post-TIPS risk, especially in male patients. Collectively, the findings advocate for a cautious application of ReMELD-Na in clinical decision-making and emphasize the need to develop sex-sensitive, multidimensional prognostic tools to improve patient selection and surveillance.

Background & Aims : Hepatic failure frequently requires liver biopsy for etiologic classification and delimitation from differential diagnoses to inform treatment decisions. Both mini-laparoscopic (MB) and transjugular liver biopsy (TB) are considered safe diagnostic modalities in liver cirrhosis (LC) patients but may associate with varying success and complication rates. We aimed to characterize the clinical values of MB and TB in patients with LC and particularly acute-on chronic liver failure (ACLF), where clinical acuity and patient risk are high. Methods : In this retrospective study, we analyzed 73 consecutive adult ACLF patients undergoing liver biopsy (57x ACLF-MB, 16x ACLF-TB) , and performed 1:2-matching with non-ACLF LC patients for either biopsy modality to assess technical success, complications, and diagnostic versatility. Results : LC severity was comparable between biopsy groups (MELD-Score ACLF-MB 27.9 points vs. ACLF-TB: 26.1 points, p=n.s.). MB and TB were successfully completed in the large majority (MB 169/171 vs. TB 48/48; p=n.s.) of procedures. While the presence of ACLF associated with a higher rate of minor complications following MB (ACLF-MB: 80.7% vs LC-MB: 52.6%, p<0.001), major biopsy-related complications were generally rare, and their occurrence did not differ between biopsy modalities. MB-specimens were technically evaluable in 100% of cases, contrasting 31.3% of technical failures in ACLF-TB and 37.5% in LC-TB (all p<0.001), respectively. In suitable biopsies, failure to obtain a histological diagnosis was observed in 3.6% of ACLF-MB, 6.2% of ACLF-TB, 17.7% of LC-MB, and 6.2% of LC-TB cases, ultimately resulting in decidely higher rates of established or corrected diagnoses via MB than TB. Conclusions : MB provides substantially higher diagnostic yield than TB at the cost of increased minor complication rates in ACLF and may be the preferred route of liver biopsy in end-stage chronic liver disease.

BACKGROUND:Decompensated cirrhosis is associated with cirrhosis-associated immune dysfunction (CAID), predisposing patients to bacterial infections and poor outcomes. The mechanisms driving CAID remain incompletely understood. OBJECTIVE:To examine whether portal hypertension (PH) is a key upstream driver of CAID and whether its reduction by transjugular intrahepatic portosystemic shunt (TIPS) reverses immune dysfunction. DESIGN:In a prospective cohort study, patients undergoing TIPS (n=75) and controls with compensated cirrhosis (n=15) were included. Plasma markers of gut barrier dysfunction, bacterial translocation, systemic inflammation and monocyte activation were measured in controls and longitudinally before and after TIPS. The effects of patient sera from different stages of cirrhosis on healthy donor-derived monocytes were assessed in vitro. Bulk RNA sequencing was performed on patient monocytes. Immunological findings were correlated with clinical outcomes, which were also validated in an external prospective cohort and a retrospective multicentre cohort of 1180 patients. RESULTS:Patients with decompensated cirrhosis showed elevated markers of gut barrier dysfunction, bacterial translocation, systemic inflammation and monocyte activation compared with compensated controls. These markers significantly decreased after TIPS. Sera from decompensated patients, but not from post-TIPS patients, induced anti-inflammatory markers (MER Tyrosine Kinase (MERTK), CD163) and suppressed interleukin 6 secretion in monocytes in vitro. Transcriptomic analysis identified an anti-inflammatory monocyte signature in decompensated cirrhosis that resolved after TIPS. CAID improvement occurred only in patients with ascites resolution and was associated with fewer bacterial infections. CONCLUSION:PH is a central driver of CAID in decompensated cirrhosis. Its reduction by TIPS restores gut barrier integrity, reduces inflammation and re-establishes immune homeostasis.

BACKGROUND AND AIMS:Clinically significant portal hypertension in patients with liver cirrhosis can lead to refractory ascites. A TIPS treats clinically significant portal hypertension but may cause overt hepatic encephalopathy (oHE). Our aim was to determine the optimal reduction of the portal pressure gradient (PPG) through TIPS to control ascites without raising oHE risk. APPROACH AND RESULTS:This multicenter study screened 1509 patients from 3 European centers (Hannover, Vienna, and Hamburg) undergoing TIPS implantation between 2000 and 2023. Patients with TIPS indications other than refractory ascites/hepatic hydrothorax, vascular liver disease, HCC, or insufficient PPG data were excluded. PPG was measured before and after TIPS insertion. Outcome data were assessed up to 1 year after TIPS insertion. Analyses were conducted utilizing a modern machine learning model, namely a competing-risk random survival forest, partial dependence plots, and competing risk analyses with liver transplantation/death as competitors. The cohort was divided into a 60% derivation and 40% validation cohort. Overall, 729 patients (median MELD: 13 [IQR 10-16], 66% male, 23% oHE before TIPS) were analyzed. The derivation cohort comprised 438 patients, and the validation cohort comprised 291 patients. The optimal PPG reduction, determined by maximally selected Gray statistic and PDP of the random survival forest, was 60%-80%. In this range, patients showed significantly fewer hepatic decompensations due to ascites (HDA) (subdistribution hazard ratio [sHR]: 0.7 [0.52-0.96]) with similar oHE incidences (sHR: 0.92 [0.67-1.27]). The PPG range was confirmed in the validation cohort (HDA: sHR: 0.66 [0.46-0.96]; oHE: sHR: 0.89 [0.61-1.32]). CONCLUSIONS:A targeted PPG reduction of 60%-80% showed significantly reduced HDA without increased oHE risk. Therefore, PPG reduction within this range could be a valid reduction target.

Background & Aims: The Freiburg index of post-TIPS survival (FIPS) defines a high-risk group of patients with significantly reduced survival following transjugular intrahepatic portosystemic shunt (TIPS) implantation. However, the clinical hallmarks responsible for these patients' unfavorable outcome remain to be identified. Therefore, the present study aimed to characterize the clinical course after TIPS implantation according to the FIPS. Methods: A total of 1,359 patients with cirrhosis allocated to TIPS implantation for treatment of recurrent or refractory ascites or secondary prophylaxis of variceal bleeding from eight tertiary centers were retrospectively included. The patients' clinical course following TIPS placement was analyzed, stratified according to the FIPS. The primary study outcome was further decompensation within 90 days after TIPS; secondary outcomes were acute-on-chronic liver failure (ACLF) within 90 days and 1-year transplant-free survival. Results: Further decompensation after TIPS implantation was significantly more frequent in FIPS high-risk patients compared to low-risk patients (cumulative incidence function 0.58 vs. 0.38, p <0.001). Moreover, FIPS high-risk patients developed ACLF significantly more often (0.18 vs. 0.08; p = 0.008). Uni-and multivariable competing risk regression analyses confirmed that high-risk FIPS independently predicted further decompensation (subdistribution hazard ratio 1.974; 95% CI 1.531-2.544; p <0.001) and ACLF (subdistribution hazard ratio 2.586; 95% CI 1.449-4.616; p = 0.001) after TIPS. Importantly, further decompensation and ACLF after TIPS were associated with significantly reduced transplant-free survival. Conclusions: The present study reveals that the FIPS predicts development of further decompensation and ACLF after TIPS implantation. These events are responsible for impaired transplant-free survival in FIPS high-risk patients. These results pave the way for the development of tailored clinical management strategies. (c) 2025 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).