Dominik Bettinger

Background and Aims: Volume expansion with albumin is recommended to establish a diagnosis of hepatorenal syndrome–acute kidney injury (HRS‐AKI). The optimal duration of albumin administration is debated and requires balancing the risk of overtreatment with the need for timely diagnosis and treatment. Therefore, this study aimed to compare the impact of different albumin treatment durations on terlipressin response and the prognosis of patients with HRS‐AKI treated with terlipressin and albumin. Methods: This multicenter, retrospective secondary analysis included patients with suspected HRS‐AKI who were treated with terlipressin and albumin at 12 German centers. One hundred forty five patients were available for further analysis. The cohort was dichotomized into patients treated with albumin for < 24 h and for 24–60 h before initiation of terlipressin. Patients were followed for treatment response to terlipressin, need for haemodialysis (HD), survival, or liver transplantation (LT). Results: Median MELD score of the cohort was 25 [IQR 21; 31]. During follow‐up, 59 patients (40.7%) achieved a complete response to treatment with terlipressin, and 96 patients (66.2%) died or received an LT. Response rates to terlipressin therapy did not differ between albumin treatment groups (< 24 h vs. 24–60 h). In multivariable competing risk models, treatment duration of albumin was not associated with any response to terlipressin, considering death and LT as competing events. Of note, albumin treatment duration did not affect HD−/LT‐free survival. Conclusion: Extending albumin treatment beyond 24 h had no impact on treatment response to terlipressin and albumin or HD‐/LT‐free survival in patients with HRS‐AKI. Clinical Trial Number: NCT 06161766

INTRODUCTION: Portal hypertension characterizes decompensated cirrhosis and its complications. It may trigger acute-on-chronic liver failure (ACLF), which carries a high mortality. Transjugular intrahepatic portosystemic shunt (TIPS) is the most efficient therapy for most portal hypertension-related complications including fluid overload (FO) defined as refractory or recurrent ascites, hepatorenal syndrome, and/or hydrothorax. However, TIPS for FO in ACLF is questioned. METHODS: In this case-control study, patients from the prospective cohorts CANONIC (n = 1,324) and German TIPS-Registry (n = 724) were screened for cases of FO and matched 1:1 by sex, age, Model for End-Stage Liver Disease (MELD) score, and presence and grade of ACLF. Clinical outcomes, ACLF status, and mortality were assessed. RESULTS: The total population was 118 patients with ACLF of whom 59 received TIPS and 59 did not. The main indication for TIPS was hepatorenal syndrome (61.0%). Patients with ACLF who did not receive TIPS had a higher 28-day cumulative mortality rate (22.0% vs 5.1%, P = 0.009). At 28 days, TIPS insertion in ACLF was associated with a 78% mortality reduction (hazard ratio 0.22 [0.06–0.77]). It further led to improvement of hepatic encephalopathy and the MELD score. In addition, ACLF resolution occurred in 61% of TIPS patients with ACLF. The presence of coagulation and circulatory organ failures, and increased bilirubin, INR, MELD score, and CLIF-C OF were associated with 28-day mortality. The survival benefit of TIPS was no longer observed after 90 days. DISCUSSION: TIPS decreased the 28-day mortality of patients with FO and ACLF. Thus, TIPS should be regarded as a bridging strategy—ideally for liver transplantation.

Background and aims: Abdominal organ dysfunction after cardiac arrest may reflect impaired hepatosplanchnic perfusion. Hypoxic hepatitis (HH) can indicate severe systemic hypoperfusion and a hepatosplanchnic ischemic phenotype. We assessed the incidence and prognostic relevance of HH after conventional and extracorporeal cardiopulmonary resuscitation (CPR, ECPR), and its association with 30-day mortality, favourable neurological outcome and non-occlusive mesenteric ischemia (NOMI). Methods: We performed a retrospective single-centre cohort study of adult patients admitted after cardiac arrest between 11/2020 and 02/2026. HH was defined as peak aspartate or alanine aminotransferase ≥20 times the sex-specific upper limit of normal within 72 hours after collapse, after exclusion of primary hepatopathy. CPR and ECPR patients were analysed separately using adjusted Cox proportional hazards and logistic regression models, including 72-hour landmark analyses. Results: Among 1135 HH-classifiable patients, HH occurred in 123/904 CPR patients (13.6%) and 67/231 ECPR patients (29.0%). In the CPR cohort, HH was independently associated with higher 30-day mortality (adjusted HR 2.28, 95% CI 1.78–2.91), lower odds of favourable neurological survival (adjusted OR 0.22, 95% CI 0.12–0.38) and higher odds of NOMI (adjusted OR 7.38, 95% CI 4.05–13.45). Similar associations were observed in the ECPR cohort for mortality (adjusted HR 1.70, 95% CI 1.20–2.40), favourable neurological survival (adjusted OR 0.09, 95% CI 0.03–0.32) and NOMI (adjusted OR 3.46, 95% CI 1.76–6.80). Landmark analyses yielded consistent results. Conclusion: HH identifies a hepatosplanchnic high-risk phenotype after cardiac arrest and is independently associated with increased mortality, poor neurological outcome and NOMI.

INTRODUCTION: Nosocomial infections (NIs) in cirrhosis are associated with high mortality but could be preventable. Logistic regression (LR) models have failed to identify high-risk patients. We aimed to develop machine learning (ML) models to predict NI. METHODS: The CLEARED consortium consists of prospectively enrolled cirrhosis inpatients from >120 centers. Using day-of-admission clinical data, 3 ML approaches (random forest [RF], extreme gradient boosting, and neural networks [NNs]) were used to predict NI. Data were split 80:20 for training and testing stratified by the outcome. Models were compared using area under the receiver operating characteristic curve (AUC). RESULTS: In total, 8,263 patients (55.90 ± 13.34 years; 64.1% men) from 127 centers in 37 countries were included. NI developed in 869 (10.5%), a median of 6 (4–11) days of postadmission. Major NIs were respiratory (29.6%) and urinary tract infection (15.7%), and spontaneous bacterial peritonitis (13.5%). NIs occurred more frequently in patients from low/low-middle income countries and those with severe liver disease, alcohol etiology, and admission infections. NIs were associated with inpatient mortality (31.9% vs 8.1%, P < 0.001) and liver transplantation (4.8% vs 1.9%, P < 0.001). Although the RF model (AUC 0.69) showed good calibration (Brier score 0.09), outperforming extreme gradient boosting, neural network, and LR models (AUC 0.66 for all; LR comparison P = 0.043), no model achieved AUC ≥0.80 for clinical utility. At 10% predicted probability threshold, the RF model demonstrated only 75.4% sensitivity, 52.9% specificity, and 15.9% positive predictive value (PPV). DISCUSSION: NIs cannot be accurately predicted from day-of-admission data using ML models, even in a large, prospective, global cirrhosis cohort. Every hospitalized patient with cirrhosis should receive protocolized infection control measures.