Acute-on-chronic liver failure (ACLF) is characterised by multiorgan failure and high short-term mortality in hospitalised patients with acute decompensation of cirrhosis. Although the EASL-CLIF criteria are widely used for diagnosis and prognostication, evolving definitions of organ dysfunction and emerging therapies require updated, tailored criteria to improve diagnostic accuracy, treatment assessment, and applicability in clinical trials. We aimed to develop and validate the A-TANGO organ failure (OF) score to refine ACLF diagnosis and enhance its utility for treatment response evaluation and risk stratification. We performed a retrospective analysis of prospective observational cohorts. The derivation cohort comprised three EF-CLIF consortium studies conducted in Europe and Latin America (CANONIC, PREDICT, ACLARA; n = 3,896). Validation cohorts included one study from India (Ambi-spective study n = 2,055) and one from China (CATCH-LIFE; n = 2,568). Patients were enrolled between 2011 and 2023, with follow-up completed in 2023. The primary objective was to redefine thresholds for organ dysfunction and failure using three subscores per organ, with subscore 3 corresponding to ≥15% 28-day mortality and defining organ failure. Compared with the CLIF-C OF score, the A-TANGO OF score introduced revised thresholds for organ failure and added an ACLF grade 4 to address the wide mortality variation within CLIF-C OF grade 3. A-TANGO identified more organ failures, increasing ACLF diagnosis from 24% to 36% and improving the net reclassification index by 16%, while maintaining similar predictive accuracy for 28- and 90-day mortality. Two additional prognostic models (A-TANGO ACLF-WBC and A-TANGO ACLF-CRP) demonstrated strong associations with 28- and 90-day mortality and improved prognostic performance. Findings were confirmed in external validation cohorts. The A-TANGO OF score is a reproducible and comprehensive tool for ACLF diagnosis with preserved prognostic performance, validated across large international cohorts. It provides a robust framework for clinical trials by enabling more accurate diagnosis, reducing required sample sizes, and offering clinically meaningful endpoints such as ACLF resolution for treatment response assessment. The A-TANGO organ failure (OF) score provides a scientifically justified advancement in ACLF research by refining organ-specific dysfunction thresholds and introducing a new grade 4, thereby addressing limitations in current EASL-CLIF criteria and improving identification of high-risk patients. These findings are important for clinicians, researchers, and healthcare systems globally, as they increase detection of organ failure, enhance risk stratification, and enable more accurate prediction of short-term mortality in hospitalized patients with cirrhosis. The A-TANGO OF score and its associated prognostic scores (ACLF-WBC and ACLF-CRP) can be applied in clinical practice to guide treatment decisions, and serve as reliable, measurable endpoints in clinical trials evaluating emerging therapies. Although limitations such as missing data, cohort-specific recruitment differences, and historical classification criteria exist, the consistent and robust performance of the A-TANGO scores across large, multinational cohorts highlights their potential applicability and utility on a global scale.

Although more than one million liver transplantations have been carried out worldwide, the literature on liver resections in transplanted livers is scarce. We herein report a total number of fourteen patients, who underwent liver resection after liver transplantation (LT) between September 2004 and 2017. Hepatocellular carcinomas and biliary tree pathologies were the predominant indications for liver resection (n = 5 each); other indications were abscesses (n = 2), post-transplant lymphoproliferative disease (n = 1) and one benign tumor. Liver resection was performed at a median of 120 months (interquartile range (IQR): 56.5–199.25) after LT with a preoperative Model for End-Stage Liver Disease (MELD) score of 11 (IQR: 6.75–21). Severe complications greater than Clavien–Dindo Grade III occurred in 5 out of 14 patients (36%). We compared liver resection patients, who had a treatment option of retransplantation (ReLT), with actual ReLTs (excluding early graft failure or rejection, n = 44). Bearing in mind that late ReLT was carried out at a median of 117 months after first transplantation and a median of MELD of 32 (IQR: 17.5–37); three-year survival following liver resection after LT was similar to late ReLT (50.0% vs. 59.1%; p = 0.733). Compared to ReLT, liver resection after LT is a rare surgical procedure with significantly shorter hospital (mean 25, IQR: 8.75–49; p = 0.034) and ICU stays (mean 2, IQR: 1–8; p < 0.001), acceptable complications and survival rates.

Background: The aetiologies, complications and overall burden of cirrhosis have undergone changes in recent years. Aims: This study aimed to assess the emerging trends in cirrhosis and its complications whilst also comparing them to other major chronic health conditions. Methods: This retrospective study covering 2011–2022 was conducted at the Charité University Hospital Berlin and University Hospital Leipzig (validation cohort), Germany. ICD‐10 codes were used to identify patients with cirrhosis, its complications and comorbidities. Changes in demographics, aetiologies, complication rates and inpatient mortality were assessed. Trends were compared against major chronic health conditions. Results: 24,567 (Berlin) and 14,141 (Leipzig) inpatient admissions for cirrhosis were identified. Overall admission numbers have been decreasing; however, in‐hospital mortality and complication rates have been increasing. Alcohol‐related liver disease was persistently the most common cause of cirrhosis (42%). Mortality rates for admissions with variceal haemorrhage and gastrointestinal bleeding have increased from 15.53% and 10.53% in 2011 to 27.69% and 31.25% in 2022, respectively. Cirrhosis admissions had some of the highest rates of inpatient mortality (7.45%), despite being considerably younger and less comorbid than admissions with other chronic health conditions. Over time, the median age of admissions with other chronic diseases increased considerably more than admissions with cirrhosis. In the validation cohort, high inpatient mortality, increasing GI bleeding associated mortality, and complications rates were confirmed. Conclusion: Cirrhosis remains a significant clinical and public health challenge and is falling behind other major comorbidities with regard to inpatient outcomes. A focus on improved resource allocation and management options is warranted.