Chronic liver diseases (CLD) may progress to cirrhosis, decompensation and death. An intervening insult may lead to acute decompensation (AD); patients with AD may fulfil criteria for acute-on-chronic liver failure (AD-ACLF). While the outcome of ACLF and priority for liver transplantation have been studied, data on outcome in a non-transplant setting is sparse. We evaluated three international consensus criteria for definition of ACLF to determine the number of patients satisfying these definitions and their accuracy in predicting mortality and compare mortality in a non-transplant setting.

Total 341 consecutive patients with CLD of any etiology were enrolled and followed up. All significant clinical events and changes in laboratory data were noted to classify patients into no AD, AD-ACLF and AD-non-ACLF.

Total 150 (44%) patients had non-alcoholic fatty liver disease as etiology. As many as 197 (57.8%) patients had AD; of these, 54 (27.4%) met at least one definition of ACLF: 50 (92.6%) fulfilled EASL-CLIF criteria, 31 (57.4%) NACSELD and 22 (40.7%) APASL. The most common precipitating event (59.2%) was infection. Forty-six (13.5%) patients died during the study period - 52% of those with AD-ACLF and 12.6% with AD-non-ACLF (p < 0.00001). The accuracy of EASL-CLIF, NACSELD and APASL definitions in determining mortality was 79.7%, 86.3% and 77.7%, respectively.

Total 16% of patients with CLD developed AD-ACLF by any definition; one-half of them died. EASL-CLIF criteria identified maximum number of patients with AD-ACLF, but NACSELD criteria had highest accuracy for predicting mortality in AD-ACLF. These findings may help prioritize patients with ACLF for intensive care in the absence of easy access to liver transplantation.

/Aims: This study aimed to evaluate the performance of the Model for End-Stage Liver Disease (MELD) 3.0 for predicting mortality and liver-related complications compared with the Child-Pugh classification, albumin-bilirubin (ALBI) grade, the MELD, and the MELD sodium (MELDNa) score.

We evaluated a multicenter retrospective cohort of incorporated patients with cirrhosis between 2013 and 2019. We conducted comparisons of the area under the receiver operating characteristic curve (AUROC) of the MELD3.0 and other models for predicting 3-month mortality. Additionally, we assessed the risk of cirrhosis-related complications according to the MELD3.0 score.

A total of 3,314 patients were included. The mean age was 55.9±11.3 years, and 70.2% of the patients were male. Within the initial 3 months, 220 patients (6.6%) died, and the MELD3.0 had the best predictive performance among the tested models, with an AUROC of 0.851, outperforming the Child-Pugh classification, ALBI grade, MELD, and MELDNa. A high MELD3.0 score was associated with an increased risk of mortality. Compared with that of the group with a MELD3.0 score <10 points, the adjusted hazard ratio of the group with a score of 10-20 points was 2.176, and that for the group with a score of ≥20 points was 4.892. Each 1-point increase in the MELD3.0 score increased the risk of cirrhosis-related complications by 1.033-fold. The risk of hepatorenal syndrome showed the highest increase, with an adjusted hazard ratio of 1.149, followed by hepatic encephalopathy and ascites.

The MELD3.0 demonstrated robust prognostic performance in predicting mortality in patients with cirrhosis. Moreover, the MELD3.0 score was linked to cirrhosis-related complications, particularly those involving kidney function, such as hepatorenal syndrome and ascites.

The utilization of extracorporeal liver support systems is increasingly prevalent for the management of acute-on-chronic liver failure in clinical settings. Yet, the efficacy of these interventions in terms of tangible clinical benefits for patients remains a matter of debate, underscoring the need for meta-analysis.

An updated meta-analysis was performed to elucidate the relationship between the application of extracorporeal liver support versus standard pharmacological treatment and the prognostic endpoints of patient survival, specifically assessing 1-month and 3-month mortality rates, as well as the incidence of complications such as hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome. Literature were searched via PubMed, EMBASE, and Web of Science.

The meta-analysis revealed the following: the odds ratio for 1-month mortality was 0.63 (95% confidence interval [CIs]: 0.51-0.76), for 3-month mortality was 0.70 (95% CI: 0.61-0.81), for hepatic encephalopathy was 0.81 (95% CI: 0.67-0.97), for spontaneous bacterial peritonitis was 0.66 (95% CI: 0.44-0.99), and for hepatorenal syndrome was 0.68 (95% CI: 0.51-0.92). These results suggest that patients with acute-on-chronic liver failure undergoing extracorporeal liver support system therapy have significantly better survival rates and lower complication incidences compared to those receiving conventional drug therapy. Further subgroup analysis indicated that patients with lower model for end-stage liver disease (MELD) scores and reduced total bilirubin (Tbil) levels demonstrated greater benefits from extracorporeal hepatic support.

This study establishes that in the management of acute-on-chronic liver failure, extracorporeal liver support systems confer a survival advantage and reduce complications relative to standard pharmacotherapy.

In the current "sickest first" allocation policy for limited deceased liver grafts, identifying patients "too sick to transplant" before transplantation is crucial to optimize outcomes. This study aimed to predict futile outcomes following deceased donor liver transplantation (DDLT) in patients with model for end-stage liver disease-sodium (MELD-Na) scores ≥30.

This international multicenter study was conducted as part of the International Society of Liver Surgeons. We collected data from patients with a MELD-Na score of ≥30 who underwent DDLT. A total of 994 patients were enrolled between 2010 and 2021, including 654 from the Republic of Korea, 224 from the USA, and 116 from other regions. Futility was defined as death within 3 months or during the hospital stay following a DDLT. After exclusion, 160 (16.6%) patients were classified into a futile group and 803 (83.4%) into a non-futile group.

The MELD-Na scores collected at three time points (listing, matching, and transplantation) were comparable between the groups ( P = 0.442, P = 0.180, and P = 0.554, respectively). Regarding concomitant organ failure factors, the futile group showed a higher incidence of organ dysfunction across all measured parameters, including the use of mechanical ventilators, continuous renal replacement therapy (CRRT), pneumonia, bacteremia, and vasopressor use (all P < 0.01). Independent risk factors for futile outcome were recipient age (≥65 years), body mass index (<18.5 kg/m 2 ), mechanical ventilator use, CRRT (≥1 week), and prolonged intensive care unit stay before transplantation (≥2 weeks). The futility rate was 53.3% in patients with ≥3 risk factors ( P < 0.001). We developed a nomogram to predict futility after DDLT based on multivariate regression analysis, which showed a better predictive power than previous models.

The risk factors and new nomogram, which adequately reflect concomitant organ failure before liver transplantation, could effectively predict the risk of futile outcomes after DDLT and contribute to decision-making regarding transplantation eligibility in clinical practice.

Liver transplantation (LT) is recognized as an effective approach that offers survival benefits for patients with acute-on-chronic liver failure (ACLF). However, controversies remain regarding the LT selection criteria, and meta-analyses reporting overall survival outcomes across different ACLF severity grades are lacking.

To depict a comprehensive postoperative picture of patients with ACLF of varying severity and contribute to updating LT selection.

Systematic searches in Web of Science, EMBASE, PubMed, and Cochrane databases were performed, from inception to December 26, 2023, for studies exploring post-transplant outcomes among ACLF patients, stratified by severity grades as identified by the European Association for the Study of the Liver-Chronic Liver Failure criteria. The primary outcome of interest was the survival rate within one year, with post-transplant complications as secondary outcomes. Additionally, the subgroup analysis examined region-specific one-year survival rates.

A total of 17 studies involving 28025 participants were included. Patients with ACLF-1 and ACLF-2 have favorable survival within one year, with survival rates reaching 87% [95% confidence interval (CI): 84%-91%] and 86% (95%CI: 81%-91%), respectively. Despite the relatively lower survival (73%, 95%CI: 66%-80%) and higher incidence of infection (48%, 95%CI: 29%-67%) observed in ACLF-3 patients, their survival exceeds that of those who do not undergo LT. Moreover, post-transplant survival was highest in North America across all ACLF grades.

LT can provide survival advantages for ACLF patients. To optimize the utilization of scarce donor organs and improve prognosis, comprehensive preoperative health evaluations are essential, especially for ACLF-3 patients.

Acute-on-chronic liver failure (ACLF) is a clinical syndrome characterized by organ failure and high short-term mortality. Since its first definition in 2013, many international organizations have defined this syndrome and, till now, there has been no agreement regarding definitions and diagnostic criteria. Although the precise mechanism of ACLF is unknown, precipitant factors and the systemic inflammation response play a major role. Specific management of this high-mortality syndrome is still under development, but a general consensus in the diagnosis and management of ACLF is needed.

Acute-on-chronic liver failure (ACLF) is a complex syndrome defined by the existence of different organ failures (OFs) in patients with chronic liver disease, mainly cirrhosis. Several definitions have been proposed to define the syndrome, varying in the grade of the subjacent liver disease, the type of precipitants and the organs considered in the definition. Liver, coagulation, brain, kidney, circulatory and pulmonary are the six types of OFs proposed in the different classifications, with different prevalence worldwide. Irrespective of the definition used, patients who develop ACLF present a hyperactive immune system, profound haemodynamic disturbances and several metabolic alterations that finally lead to organ dysfunction. These disturbances are triggered by different factors such as bacterial infections, alcoholic hepatitis, gastrointestinal bleeding or hepatitis B virus flare, among others. Because patients with ACLF present high short-term mortality, a prompt recognition is needed to start treatment of the trigger event and specific organ support. Liver transplantation is also feasible in carefully selected patients and should be evaluated.

Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome characterized by decompensation of cirrhosis, severe systemic inflammation and organ failures. ACLF is frequently triggered by intra- and/or extrahepatic insults, such as bacterial infections, alcohol-related hepatitis or flares of hepatic viruses. The imbalance between systemic inflammation and immune tolerance causes organ failures through the following mechanisms: (i) direct damage of immune cells/mediators; (ii) worsening of circulatory dysfunction resulting in organ hypoperfusion and (iii) metabolic alterations with prioritization of energetic substrates for inflammation and peripheral organ 'energetic crisis'. Currently, the management of ACLF includes the support of organ failures, the identification and treatment of precipitating factors and expedited assessment for liver transplantation (LT). Early LT should be considered in patients with ACLF grade 3, who are unlikely to recover with the available treatments and have a mortality rate > 70% at 28 days. However, the selection of transplant candidates and their prioritization on the LT waiting list need standardization. Future challenges in the ACLF field include a better understanding of pathophysiological mechanisms leading to inflammation and organ failures, the development of specific treatments for the disease and personalized treatment approaches. Herein, we reviewed the current knowledge and future perspectives on mechanisms and treatment of ACLF.

Accurate prediction of survival in patients with cirrhosis is crucial, as patients who are unlikely to survive in the short-term need to be oriented to liver transplantation and to novel therapeutic approaches. Patients with acute decompensation of cirrhosis without or with organ dysfunction/failure, the so-called acute-on-chronic liver failure (ACLF), have a particularly high short-term mortality. Recognizing the specificity of this clinical situation, dedicated classifications and scores have been developed over the last 15 years, including variables (e.g. organ failures and systemic inflammation) not part of the formerly available cirrhosis severity scores, namely Child-Pugh score or MELD. For patients with acute decompensation of cirrhosis, it led to the development of a dedicated score, the Clif-C-AD score, independently validated. For more severe patients, three different scoring systems have been proposed, by European, Asian and North American societies namely Clif-C-ACLF, AARC score and NASCELD-ACLF respectively. These scores have been validated, and are widely used across the world. The differences and similarities between these scores, as well as their validation and limitations are discussed here. Even if these scores and classifications have been a step forward in favouring homogeneity between studies, and in helping making decisions for individual patients, their predictive value for mortality can still be improved as their area under the ROC curve does not exceed .8. Novel scores including biomarkers reflecting the pathophysiology of acute decompensation of cirrhosis might help reach that goal.

This narrative review addresses the definition of acute-on-chronic liver failure, a condition associated with high short-term mortality in patients with chronic liver disease and/or cirrhosis. We provide two major points of view: the East and the West perspective. Both definitions vary regarding the underlying patient population and organ failure(s) definition. Nevertheless, all the definitions have their clinical utility: from the core concept of having the "liver" as a conditio sine qua non, the syndrome cannot exist (Asian Pacific Association for the Study of the Liver); a data-driven, robust definition (European Association for the Study of the Liver); a bedside tool that can quickly identify patients at high risk of dying (North American Consortium for the Study of End-stage Liver Disease [NACSELD]). In each section, we provide the overall definitions, the criteria of organ failure(s), and some epidemiological data illustrating how these apply in each area of the world.

Drug-induced liver injury (DILI) is a global problem and can develop from exposure to prescription or over-the-counter medications as well as herbal and dietary supplements. The diagnosis of DILI is clinically challenging, and liver injury can be severe leading to liver failure, death, or liver transplantation. Patients with underlying chronic liver diseases (CLD) may be at increased risk for DILI, which is associated with factors related to drug or liver disease.

This review summarises current knowledge on the risk and outcomes of DILI in patients with CLD.

Patients with CLD may be at an increased risk for DILI. Additionally patients with underlying CLD are at risk for more severe liver injury and worse outcomes after DILI.

The risk for and poor outcomes from DILI are accentuated in patients with CLD and potentially leading to the worst-case scenario of acute-on-chronic liver failure. We highlight the key observations on DILI with a broad range of underlying liver diseases and the high-DILI risk agents implicated in those populations.

Acute on chronic liver failure (ACLF) reflects the development of organ failure(s) in a patient with cirrhosis and is associated with high short-term mortality. Given that ACLF has many different 'phenotypes', medical management needs to take into account the relationship between precipitating insult, organ systems involved and underlying physiology of chronic liver disease/cirrhosis. The goals of intensive care management of patients suffering ACLF are to rapidly recognize and treat inciting events (e.g. infection, severe alcoholic hepatitis and bleeding) and to aggressively support failing organ systems to ensure that patients may successfully undergo liver transplantation or recovery. Management of these patients is complex since they are prone to develop new organ failures and infectious or bleeding complications. ICU therapy parallels that applied in the general ICU population in some complications but differs in others. Given that liver transplantation in ACLF is an emerging and evolving field, multidisciplinary teams with expertise in critical care and transplant medicine best accomplish management of the critically ill ACLF patient. The focus of this review is to identify the common complications of ACLF and to describe the proper management in critically ill patients awaiting liver transplantation in our centres, including organ support, prognostic assessment and how to assess when recovery is unlikely.

Acute-on-chronic liver failure (ACLF) is a critical syndrome that develops in patients with chronic liver disease and is characterized by acute decompensation, single- or multiple-organ failure and high short-term mortality. Over the past few decades, ACLF has been progressively recognized as an independent clinical entity, and several criteria and prognostic scores have been proposed and validated by different scientific societies. However, controversies still exist in some aspects across regions, which mainly involve whether the definition of underlying liver diseases should include cirrhosis and non-cirrhosis. The pathophysiology of ACLF is complicated and remains unclear, although accumulating evidence based on different aetiologies of ACLF shows that it is closely associated with intense systemic inflammation and immune-metabolism disorder, which result in mitochondrial dysfunction and microenvironment imbalance, leading to disease development and organ failure. In-depth insight into the biological pathways involved in the mechanisms of ACLF and potential mechanistic targets that improve patient survival still needs to be investigated. Omics-based analytical techniques, including genomics, transcriptomics, proteomics, metabolomics and microbiomes, have developed rapidly and can offer novel insights into the essential pathophysiologic process of ACLF. In this paper, we briefly reviewed and summarized the current knowledge and recent advances in the definitions, criteria and prognostic assessments of ACLF; we also described the omics techniques and how omics-based analyses have been applied to investigate and characterize the biological mechanisms of ACLF and identify potential predictive biomarkers and therapeutic targets for ACLF. We also outline the challenges, future directions and limitations presented by omics-based analyses in clinical ACLF research.

The aim is to explore significant prognostic factors for 90-day mortality in patients with acute-on-chronic liver failure (ACLF) and assist clinicians in the early identification of critically ill ACLF patients.

A retrospective analysis was conducted on 288 ACLF patients, who were classified into survivors (n = 187) and nonsurvivors (n = 101) based on 90-day outcomes. Multivariate stepwise logistic regression analyses were employed to identify significant prognostic factors and construct a novel prognostic model, the AHUCTPI. The model's performance was assessed and the internal validation was performed. Additionally, the influence of dynamic changes in laboratory markers on 90-day mortality was examined.

Independent risk factors for 90-day mortality included age ≥45 years, presence of hepatic encephalopathy (HE), and upper gastrointestinal bleeding (UGB) during hospitalization, imaging-confirmed cirrhosis at admission, elevated baseline total bilirubin (TBIL), reduced baseline platelet-to-neutrophil ratio (PNR), and elevated baseline international normalized ratio (INR) (P < 0.05 for all). The AHUCTPI model's formula is as follows: Logit (p) = -10.019 + 1.808 × age (1 if ≥45 years, 0 if <45 years) + 1.048 × HE (1 if present, 0 if absent) + 1.721 × UGB (1 if present, 0 if absent) + 1.362 × cirrhosis (1 if present, 0 if absent) + 0.008 × TBIL (μmol/L) - 0.039 × PNR + 1.963 × INR. The AUHCTPI model demonstrated superior predictive accuracy compared with the MELD (Model for End-Stage Liver Disease) score, with the area under the receiver operating characteristic curve values of 0.914 and 0.739, respectively, and calibration curves closely approximating the ideal curve.

ACLF is a complex, dynamic syndrome. Age, HE, and UGB during hospitalization, imaging-diagnosed cirrhosis at admission, baseline TBIL, PNR, and INR were significant predictors for 90-day mortality in ACLF patients, and the AHUCTPI model provides excellent calibration and discrimination. Dynamic monitoring of laboratory trends enhances prognostic accuracy and supports timely clinical decision-making.

Acute-on-chronic liver failure (ACLF) is a severe syndrome that manifests as acute liver function deterioration and organ failure. Coinfection with invasive pulmonary aspergillosis (IPA) in ACLF patients is characterized by high mortality and increasing morbidity. The aim of this study was to explore the early warning factors and prognosis of ACLF patients with IPA coinfection.

In this retrospective study, we collected clinical, biochemical, and microbiological data from patients with ACLF and IPA from May 2019 to May 2023. Univariable and multivariate analyses were used to identify independent risk factors for IPA in ACLF patients. Moreover, the area under the curve (AUC) and decision curve analysis (DCA) were used to evaluate the model performance.

A total of 438 patients with ACLF were enrolled, 408 (93.2%) non-IPA patients and 30 IPA (6.8%) including 29 probable cases and one proven case. The 28-day case fatality rate (56.7% vs 29.4%) was higher in ACLF patients with IPA than in ACLF patients without IPA, but without statistical difference. Multivariate analysis revealed that early warning factors for IPA coinfection in ACLF patients included nausea (p = 0.010), expectoration (p < 0.001), bacterial and fungal infections (p < 0.001), corticosteroid use (p = 0.037), surgery (p = 0.081), haemoptysis (p = 0.015) and increased leukocyte counts (p = 0.010). The AUC was 0.934 (p < 0.001), and DCA verified the validity and clinical effectiveness of our model.

These findings provide valuable insights for clinicians in the early diagnosis of IPA in ACLF patients and may facilitate timely intervention and treatment.

We investigated the occurrence and outcome of respiratory failure and ARDS in critically ill patients with liver cirrhosis. This is a retrospective analysis of patients with liver cirrhosis at an ICU during an 8-Year period. An assessment of acute on chronic liver failure as well as the presence and grade of ARDS within the first 72 h of admission to the ICU was performed. A total of 735 patients during the study period. Median age was 58 (50-69) years and 61% (n = 447) were male. 57% (n = 421) of the patients received mechanical ventilation (MV). Liver specific as well as ICU scores on admission were significantly higher in patients with MV. Necessity of vasopressor support (86%vs.25%, p < 0.001) and RRT (50%vs.11%, p < 0.001) was more frequent in patients with MV. The incidence of ARDS within the first 72 h of admission was 8% (n = 61). We observed a 28-day mortality or liver transplantation rate of 54% (n = 196) and 66% (n = 66%) in patients with MV and ARDS, respectively. After 90-days 63% (n = 226) with MV and 70% (n = 43) with ARDS were dead or received liver transplantation. ARDS is a prognostic factor for mortality in patients with liver cirrhosis admitted to the ICU. One out of ten critically ill cirrhotic patients develop ARDS within 72 h after admission. Although mortality rates are high initially critical care therapy should not be withheld and must be reevaluated regularly.

Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the "APASL ACLF Research Consortium (AARC)" was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia-Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the 'Golden Therapeutic Window', the 'transplant window', and plasmapheresis as a treatment modality. Also, the data has been key to identifying pediatric ACLF. The European Association for the Study of Liver-Chronic Liver Failure (EASL CLIF) and the North American Association for the Study of the End Stage Liver Disease (NACSELD) from the West added the concepts of organ failure and infection as precipitants for the development of ACLF and CLIF-Sequential Organ Failure Assessment (SOFA) and NACSELD scores for prognostication. The Chinese Group on the Study of Severe Hepatitis B (COSSH) added COSSH-ACLF criteria to manage hepatitis b virus-ACLF with and without cirrhosis. The literature supports these definitions to be equally effective in their respective cohorts in identifying patients with high mortality. To overcome the differences and to develop a global consensus, APASL took the initiative and invited the global stakeholders, including opinion leaders from Asia, EASL and AASLD, and other researchers in the field of ACLF to identify the key issues and develop an evidence-based consensus document. The consensus document was presented in a hybrid format at the APASL annual meeting in Kyoto in March 2024. The 'Kyoto APASL Consensus' presented below carries the final recommendations along with the relevant background information and areas requiring future studies.

Very recently, we creatively put forward a new classification for ACLF patients, which lays the foundation for the establishment of prognostic model that can accurately predict the prognosis of ACLF patients. Herein, we found: galectin-3 levels were higher in type A ACLF patients compared to those of type B patients; galectin-3 expression was closely correlated with TBil, PTA/INR and MELD; galectin-3 is an independent predictive factor for rapid progression in ACLF, and exhibited superior predictive value for the prognosis of type A ACLF patients than MELD score; and the survival rate was remarkably higher in ACLF patients with lower galectin-3 expression. Collectively, galectin-3 can be considered as a non-invasive biomarker to predict the prognosis of ACLF patients with new typing. Our findings help advance the time window of prognosis prediction for type A and type B ACLF patients from 4 weeks to the baseline, thereby identifying ACLF patients who really need liver transplantation earlier and improving the survival of ACLF patients.

Bacterial infections are a leading cause of hospitalization and mortality in patients with decompensated cirrhosis. Antibiotic prophylaxis in cirrhotic patients has demonstrated significant short-term reductions in bacterial infections in randomized controlled trials, but at the cost of drug resistance and with uncertain survival benefits.

This review examines antibiotic use in cirrhosis, focusing on patients most likely to benefit from antibiotic prophylaxis, management strategies for infections through risk-based antibiotic selection and timely treatment initiation, challenges posed by the emergence of multidrug-resistant organisms, and principles of antimicrobial stewardship.

The efficacy of prophylaxis has decreased over time, and current registry data have questioned its use, emphasizing the need for better risk-based individualized strategies. When bacterial infections occur, the efficacy of antimicrobial therapies depends heavily on local epidemiological patterns and individual patient risk factors, necessitating tailored antibiotic selection based on regional resistance data and specific clinical scenarios. Nosocomial infections, colonization with multidrug-resistant organisms, and prior exposure to systemic antibiotics are key risk factors that should guide empirical therapy selection. Until evidence-based algorithms are available, clinicians should continue to adopt individualized approaches, guided by available evidence, local specificities, and antimicrobial stewardship principles to optimize patient outcomes.

Acute kidney injury (AKI) requiring continuous renal replacement therapy is common in critically ill patients. The ADVanced Organ Support (ADVOS) system is a novel hemodialysis machine that uses albumin enriched dialysate which allows the removal of protein-bound toxins and drugs. To date, data on antimicrobial removal under ADVOS has not yet been reported.

An in vitro study was conducted using whole porcine blood and continuous infusions of different antimicrobial agents to investigate the effect of ADVOS on drug exposure. Drugs with varying protein binding, molecular weights and renal clearances, anidulafungin, cefotaxime, daptomycin, fluconazole, ganciclovir, linezolid, meropenem and piperacillin were studied.

All studied drugs were removed during the in vitro ADVOS experiment. Clearance under ADVOS (CLADVOS) for low protein-bound drugs, such as cefotaxime, fluconazole, ganciclovir, linezolid, meropenem and piperacillin ranged from 2.74 to 3.4 L/h at a blood flow of 100 mL/min. With a doubling of flow rate CL for these drugs increased. Although efficiently removed, this effect was not seen for CLADVOS in high protein-bound substances such as daptomycin (1.36 L/h) and anidulafungin (0.84 L/h).

The ADVOS system effectively removed protein-bound and unbound antimicrobials to a significant extent indicating that dose adjustments are required. Further, clinical studies are necessary to comprehensively assess the impact of ADVOS on antimicrobial drug removal. Until clinical data are available, therapeutic drug monitoring should guide antimicrobial dosing under ADVOS.

Despite the poor prognosis associated with missed or delayed spontaneous bacterial peritonitis (SBP) diagnosis, <15% get timely paracentesis, which persists despite guidelines/education in the United States. Measures to exclude SBP non-invasively where timely paracentesis cannot be performed could streamline this burden.

Using Veterans Health Administration Corporate Data Warehouse (VHA-CDW) we included patients with cirrhosis between 2009 and 2019 who underwent timely paracentesis and collected relevant clinical information (demographics, cirrhosis severity, medications, vitals, and comorbidities). XGBoost-models were trained on 75% of the primary cohort, with 25% reserved for testing. The final model was further validated in 2 cohorts: Validation cohort #1: In VHA-CDW, those without prior SBP who received 2nd early paracentesis, and Validation cohort #2: Prospective data from 276 non-electively admitted University hospital patients.

Negative predictive values (NPVs) at 5%,10%, and 15% probability cutoffs were examined. Primary cohort: n = 9643 (mean age, 63.1 ± 8.7 years; 97.2% men; SBP, 15.0%) received first early paracentesis. Testing-set NPVs for SBP were 96.5%, 93.0%, and 91.6% at the 5%, 10%, and 15% probability thresholds, respectively. In Validation cohort #1: n = 2844 (mean age, 63.14 ± 8.37 years; 97.1% male; SBP, 9.7%) with NPVs were 98.8%, 95.3%, and 94.5%. In Validation cohort #2: n = 276 (mean age, 56.08 ± 9.09; 59.6% male; SBP, 7.6%) with NPVs were 100%, 98.9%, and 98.0% The final machine learning model showed the greatest net benefit on decision-curve analyses.

A machine learning model generated using routinely collected variables excluded SBP with high NPV. Applying this model could ease the need to provide paracentesis in resource-limited settings by excluding those unlikely to have SBP.

Hyponatremia can worsen the outcomes of patients with liver cirrhosis. However, it remains unclear about how to predict the risk of death in cirrhotic patients with hyponatremia. Patients with liver cirrhosis and hyponatremia were screened. Eligible patients were randomly divided into the training (n = 472) and validation (n = 471) cohorts. In the training cohort, the independent predictors for in-hospital death were identified by logistic regression analyses. Odds ratios (ORs) were calculated. An artificial neural network (ANN) model was established in the training cohort. Areas under curve (AUCs) of ANN model, Child-Pugh, model for end-stage liver disease (MELD), and MELD-Na scores were calculated by receiver operating characteristic curve analyses. In multivariate logistic regression analyses, ascites (OR = 2.705, P = 0.042), total bilirubin (OR = 1.004, P = 0.003), serum creatinine (OR = 1.004, P = 0.017), and international normalized ratio (OR = 1.457, P = 0.005) were independently associated with in-hospital death. Based on the four variables, an ANN model was established. Its AUC was 0.865 and 0.810 in the training and validation cohorts, respectively, which was significantly larger than those of Child-Pugh (AUC = 0.757), MELD (AUC = 0.765), and MELD-Na (AUC = 0.769) scores. An ANN model has been developed and validated for the prediction of in-hospital death in patients with liver cirrhosis and hyponatremia.

Acute liver failure (ALF) and acute-on-chronic liver (ACLF) are distinct phenotypes of liver failure and, thus, need to be compared and contrasted for appropriate management. There has been a significant improvement in the outcomes of these patients undergoing liver transplantation (LT). Survival post-LT for ALF and ACLF ranges between 90% and 95% and 80% and 90% at 1 year, futility criteria have been described in both ALF and ACLF where organ failures define survival. Plasma exchange and continuous renal replacement therapy may serve as bridging therapies. Identifying the futility of LT is as necessary as the utility of LT in patients with ALF and ACLF. The role of regenerative therapies such as granulocyte colony-stimulating factors in ACLF and hepatocyte and xenotransplantation in both conditions remains uncertain. Measures to increase the donor pool through increasing deceased donor transplants in Asian countries, living donations in Western countries, auxiliary liver transplants, and ABO-incompatible liver transplants are necessary to improve the survival of these patients. In this review, we discuss the similarities and differences in clinical characteristics and the timing and outcomes of LT for ALF and ACLF, briefly highlighting the role of bridging therapies and providing an overview of recent advances in the management of ALF and ACLF.

Acute-on-chronic liver failure (ACLF) is defined as a clinical syndrome that develops in patients with chronic liver disease characterized by the presence of organ failure and high short-term mortality, although there is still no worldwide consensus on diagnostic criteria. Management of ACLF is mainly based on treatment of "precipitating factors" (the most common are infections, alcohol-associated hepatitis, hepatitis B flare, and bleeding) and support of organ failure, which often requires admission to the intensive care unit. Liver transplantation should be considered in patients with ACLF grades 2 to 3 as a potentially life-saving treatment. When a transplant is not indicated, palliative care should be considered after 3 to 7 days of full organ support in patients with at least four organ failures or a CLIF-C ACLF score of >70. This review summarizes the current knowledge on the management of organ failure in patients with ACLF, focusing on recent advances.

Acute-on-chronic liver failure (ACLF) is a major public health concern. We aimed to assess the definitions, etiologic spectrum, organ failure (OF), and outcomes of ACLF globally.

Three databases were searched for studies on ACLF from 1990 until September 2022. Information regarding definitions, acute precipitants, underlying chronic liver disease (CLD), OF, and mortality were extracted. Meta-analyses were performed for pooled prevalence rates (95% confidence interval [CI]) using random-effects model for each definition of ACLF.

Of the 11,451 studies identified, 114 articles (142 cohorts encompassing 210,239 patients) met the eligibility criteria. Most studies (53.2%) used the European Association for the Study of the Liver (EASL) definition, followed by Asia-Pacific Association for the Study of the Liver (APASL) (33.3%). Systemic infection was the major acute precipitant, and alcohol use was the major cause of CLD in EASL-defined studies, whereas alcohol was both the major acute precipitant and cause of CLD in APASL-defined studies. Liver failure was the major OF in APASL-based studies, whereas renal failure was predominant in EASL-based studies. Thirty-day mortality varied across definitions: APASL: 38.9%, 95% CI, 31.2%-46.9%; EASL: 47.9%, 95% CI, 42.2%-53.5%; and NACSELD: 52.2%, 95% CI, 51.9%-52.5%. Diagnostic overlap between definitions ranged from 7.7% to 80.2%. Meta-regression suggested that the World Health Organization region influenced 30-day mortality in studies using EASL definition.

Heterogeneity in the definition of ACLF proposed by different expert societies and regional preferences in its use result in differences in clinical phenotype and outcomes. A uniform definition would enhance the comparability and interpretation of global data.