Chronic Liver Failure Consortium Acute-on-chronic Liver Failure Research Articles

Development and validation of a new prognostic model for patients with acute-on-chronic liver failure in intensive care unit.

Cirrhotic patients with acute-on-chronic liver failure (ACLF) in the intensive care unit (ICU) have a poor but variable prognoses. Accurate prognosis evaluation can guide the rational management of patients with ACLF. However, existing prognostic scores for ACLF in the ICU environment lack sufficient accuracy. To develop a new prognostic model for patients with ACLF in ICU. Data from 938 ACLF patients in the Medical Information Mart for Intensive Care (MIMIC) database were used to develop a new prognostic model (MIMIC ACLF) for ACLF. Discrimination, calibration and clinical utility of MIMIC ACLF were assessed by area under receiver operating characteristic curve (AUROC), calibration curve and decision curve analysis (DCA), respectively. MIMIC ACLF was then externally validated in a multiple-center cohort, the Electronic Intensive Care Collaborative Research Database and a single-center cohort from the Second Hospital of Hebei Medical University in China. The MIMIC ACLF score was determined using nine variables: ln (age) × 2.2 + ln (white blood cell count) × 0.22 - ln (mean arterial pressure) × 2.7 + respiratory failure × 0.6 + renal failure × 0.51 + cerebral failure × 0.31 + ln (total bilirubin) × 0.44 + ln (internationalized normal ratio) × 0.59 + ln (serum potassium) × 0.59. In MIMIC cohort, the AUROC (0.81/0.79) for MIMIC ACLF for 28/90-day ACLF mortality were significantly greater than those of Chronic Liver Failure Consortium ACLF (0.76/0.74), Model for End-stage Liver Disease (MELD; 0.73/0.71) and MELD-Na (0.72/0.70) (all P < 0.001). The consistency between actual and predicted 28/90-day survival rates of patients according to MIMIC ACLF score was excellent and superior to that of existing scores. The net benefit of MIMIC ACLF was greater than that achieved using existing scores within the 50% threshold probability. The superior predictive accuracy and clinical utility of MIMIC ACLF were validated in the external cohorts. We developed and validated a new prognostic model with satisfactory accuracy for cirrhotic patients with ACLF hospitalized in the ICU. The model-based risk stratification and online calculator might facilitate the rational management of patients with ACLF.

Accuracy of chronic liver failure consortium (CLIF-C) ACLF score compared with meld, MELD-NA and CTP as a mortality predictor in acute on chronic liver failure patients admitted to tertiary rural care hospital

Background Chronic Liver Failure Consortium (CLIF-C) ACLF score, Model for End-Stage Liver Disease (MELD), MELD-Na, and Child-Pugh (CTP) are established scoring systems for predicting mortality in Acute on Chronic Liver Failure (ACLF) patients. However, their comparative accuracy, especially in rural care settings, still needs to be explored. This study aims to assess and compare the predictive performance of these scoring systems, providing a nuanced understanding of their applicability in a tertiary rural care hospital. Method This prospective observational cohort study will be conducted at Acharya Vinoba Bhave Rural Hospital, following approval from the institutional ethical committee. ACLF patients aged 18 and above, presenting within one week of onset, will be included. Data collection will involve comprehensive assessments, including scoring system calculations, clinical examinations, and relevant investigations. Statistical analyses, encompassing descriptive statistics, comparative analyses, survival analyses, and multivariate models, will elucidate the accuracy and independent predictors of 28-day mortality. Expected Outcome Anticipated outcomes include a comprehensive understanding of the strengths and limitations of the CLIF-C ACLF score, MELD, MELD-Na, and CTP in predicting mortality among ACLF patients in a rural care context. The study aims to identify potential correlations and independent predictors, offering valuable insights for risk stratification. These findings are expected to guide clinicians in optimising prognostic assessments and decision-making, thereby improving the care and outcomes of ACLF patients in rural healthcare settings.

Thromboelastography characteristics in critically ill patients with liver disease.

The purpose of this study was to determine how thromboelastography (TEG) parameters differ by various clinical conditions that commonly occur in patients with cirrhosis, including sepsis, acute on chronic liver failure (ACLF), alcohol-associated hepatitis (AAH) and portal vein thrombosis (PVT). TEG, a whole blood assay, is used to assess several parameters of coagulation and is becoming increasingly used in clinical practice. This study was a retrospective chart review of 155 patients admitted to the ICU with decompensated cirrhosis from 2017 to 2019. The R time was significantly shorter in patients when they were septic compared to when they were not and longer in patients with vs. without ACLF grade 3. Alpha angle and maximum amplitude was decreased in patients with severe AAH compared to those without severe AAH; and maximum amplitude was increased in patients with acute PVT compared to those with chronic PVT. R time was positively correlated with Chronic Liver Failure Consortium Organ Failure and Chronic Liver Failure Consortium ACLF scores (rho = 0.22, P = 0.020), while alpha angle and maximum amplitude were negatively correlated with MELD-NA. Findings suggest TEG parameters vary in several clinical conditions in patients with decompensated cirrhosis who are admitted to the ICU. Prospective research is needed to confirm our findings and to determine how this knowledge can be used to guide clinical practice, as well as blood product transfusions in the setting of bleeding or prior to invasive procedures.

Neutrophilia is more predictive than increased white blood cell counts for short-term mortality after liver transplantation in patients with acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) is a life-threatening disease that requires urgent liver transplantation (LT). Accurate identification of high-risk patients is essential for predicting post-LT survival. The chronic liver failure consortium ACLF score is a widely accepted risk-stratification score that includes total white blood cell (WBC) counts as a component. This study aimed to evaluate the predictive value of total and differential WBC counts for short-term mortality following LT in patients with ACLF. A total of 685 patients with ACLF who underwent LT between January 2008 and February 2019 were analyzed. Total and differential WBC counts were examined as a function of the model for end-stage liver disease for sodium (MELD-Na) score. The association between total and differential WBC counts and 90-day post-LT mortality was assessed using multivariable Cox proportional hazards regression analysis. The total WBC counts and neutrophil ratio were higher in patients with ACLF than in those without ACLF. The neutrophil ratio was significantly associated with 90-day post-LT mortality after adjustment (hazard ratio [HR], 1.04; P = 0.001), whereas total WBC counts were not significantly associated with 90-day post-LT mortality in either univariate or multivariate Cox analyses. The neutrophil ratio demonstrated a relatively linear trend with an increasing MELD-Na score and HR for 90-day post-LT mortality, whereas the total WBC counts exhibited a plateaued pattern. Neutrophilia, rather than total WBC counts, is a better prognostic indicator for short-term post-LT mortality in patients with ACLF.

Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on- chronic liver failure

Acute-on-chronic liver failure (ACLF) is characterized by severe systemic inflammation, multi-organ failure and high mortality rates. Its treatment is an urgent unmet need. DIALIVE is a novel liver dialysis device that aims to exchange dysfunctional albumin and remove damage- and pathogen-associated molecular patterns. This first-in-man randomized-controlled trial was performed with the primary aim of assessing the safety of DIALIVE in patients with ACLF, with secondary aims of evaluating its clinical effects, device performance and effect on pathophysiologically relevant biomarkers. Thirty-two patients with alcohol-related ACLF were included. Patients were treated with DIALIVE for up to 5 days and end points were assessed at Day 10. Safety was assessed in all patients (n= 32). The secondary aims were assessed in a pre-specified subgroup that had at least three treatment sessions with DIALIVE (n= 30). There were no significant differences in 28-day mortality or occurrence of serious adverse events between the groups. Significant reduction in the severity of endotoxemia and improvement in albumin function was observed in the DIALIVE group, which translated into a significant reduction in the CLIF-C (Chronic Liver Failure consortium) organ failure (p= 0.018) and CLIF-C ACLF scores (p= 0.042) at Day 10. Time to resolution of ACLF was significantly faster in DIALIVE group (p= 0.036). Biomarkers of systemic inflammation such as IL-8 (p= 0.006), cell death [cytokeratin-18: M30 (p= 0.005) and M65 (p= 0.029)], endothelial function [asymmetric dimethylarginine (p= 0.002)] and, ligands for Toll-like receptor 4 (p= 0.030) and inflammasome (p= 0.002) improved significantly in the DIALIVE group. These data indicate that DIALIVE appears to be safe and impacts positively on prognostic scores and pathophysiologically relevant biomarkers in patients with ACLF. Larger, adequately powered studies are warranted to further confirm its safety and efficacy. This is the first-in-man clinical trial which tested DIALIVE, a novel liver dialysis device for the treatment of cirrhosis and acute-on-chronic liver failure, a condition associated with severe inflammation, organ failures and a high risk of death. The study met the primary endpoint, confirming the safety of the DIALIVE system. Additionally, DIALIVE reduced inflammation and improved clinical parameters. However, it did not reduce mortality in this small study and further larger clinical trials are required to re-confirm its safety and to evaluate efficacy. NCT03065699.

Validation of the CLIF-C OF Score and CLIF-C ACLF Score to Predict Transplant-Free Survival in Patients with Liver Cirrhosis and Concomitant Need for Intensive Care Unit Treatment.

Both the Chronic Liver Failure Consortium (CLIF-C) organ failure score (OFs) and the CLIF-C acute-on-chronic-liver failure (ACLF) score (ACLFs) were developed for risk stratification and to predict mortality in patients with liver cirrhosis and ACLF. However, studies validating the predictive ability of both scores in patients with liver cirrhosis and concomitant need for intensive care unit (ICU) treatment are scarce. The aim of the present study is to validate the predictive ability of the CLIF-C OFs and CLIF-C ACLFs regarding the rationale of ongoing ICU treatment and to investigate their predictive ability regarding 28-days (short-), 90-days (medium-), and 365-days (long-term) mortality in patients with liver cirrhosis treated in an ICU. Patients with liver cirrhosis and acute decompensation (AD) or ACLF and concomitant need for ICU treatment were retrospectively analyzed. Predictive factors for mortality, defined as transplant-free survival, were identified using multivariable regression analyses and the predictive ability of CLIF-C OFs, CLIF-C ACLFs, MELD score, and AD score (ADs) was assessed by determining the AUROC. Of 136 included patients, 19 patients presented with AD and 117 patients with ACLF at ICU admission. In multivariable regression analyses, CLIF-C OFs as well as CLIF-C ACLFs were independently associated with higher short-, medium-, and long-term mortality after adjusting for confounding variables. The predictive ability of the CLIF-C OFs in the total cohort in short-term was 0.687 (95% CI 0.599-0.774). In the subgroup of patients with ACLF, the respective AUROCs were 0.652 (95% CI 0.554-0.750) and 0.717 (95% CI 0.626-0.809) for the CLIF-C OFs and for the CLIF-C ACLFs, respectively. ADs performed well in the subgroup of patients without ACLF at ICU admission with an AUROC of 0.792 (95% CI 0.560-1.000). In the long-term, the AUROCs were 0.689 (95% Cl 0.581-0.796) and 0.675 (95% Cl 0.550-0.800) for CLIF-C OFs and CLIF-C ACLFs, respectively. The predictive ability of CLIF-C OFs and CLIF-C ACLFs was relatively low to predict short- and long-term mortality in patients with ACLF with concomitant need for ICU treatment. However, the CLIF-C ACLFs may have special merit in judging futility of further ICU treatment.

FATORES PROGNÓSTICOS DE TRANSPLANTE HEPÁTICO EM “ACUTE-ON-CHRONIC LIVER FAILURE”

ABSTRACT BACKGROUND: Liver transplantation (LT) is the only treatment that can provide long-term survival for patients with acute-on-chronic liver failure (ACLF). Although several studies identify prognostic factors for patients in ACLF who do not undergo LT, there is scarce literature about prognostic factors after LT in this population. AIM: Evaluate outcomes of ACLF patients undergoing LT, studying prognostic factors related to 1-year and 90 days post-LT. METHODS: Patients with ACLF undergoing LT between January 2005 and April 2021 were included. Variables such as chronic liver failure consortium (CLIF-C) ACLF values and ACLF grades were compared with the outcomes. RESULTS: The ACLF survival of patients (n=25) post-LT at 90 days, 1, 3, 5 and 7 years, was 80, 76, 59.5, 54.1 and 54.1% versus 86.3, 79.4, 72.6, 66.5 and 61.2% for patients undergoing LT for other indications (n=344), (p=0.525). There was no statistical difference for mortality at 01 year and 90 days among patients with the three ACLF grades (ACLF-1 vs. ACLF-2 vs. ACLF-3) undergoing LT, as well as when compared to non-ACLF patients. CLIF-C ACLF score was not related to death outcomes. None of the other studied variables proved to be independent predictors of mortality at 90 days, 1 year, or overall. CONCLUSIONS: LT conferred long-term survival to most transplant patients. None of the studied variables proved to be a prognostic factor associated with post-LT survival outcomes for patients with ACLF. Additional studies are recommended to clarify the prognostic factors of post-LT survival in patients with ACLF.

Hepatic perfusion as a new predictor of prognosis and mortality in critical care patients with acute-on-chronic liver failure.

Background and aimsLiver diseases are frequent causes of morbidity and mortality worldwide. Liver diseases can lead to cirrhosis, with the risk of acute-on-chronic liver failure (ACLF). For the detection of changes in hepatic hemodynamics, Doppler ultrasonography is a well-established method. We investigated hepatic hemodynamics via serial Doppler ultrasonography to determine the predictive value of changes in hepatic perfusion for the outcome in patients with severe liver diseases compared to established prognostic models such as the MELD (Model for End-Stage Liver Disease) or CLIF-C (Chronic Liver Failure-Consortium) ACLF score.MethodsIn this prospective cohort study, hepatic perfusion was quantified at baseline before the initiation of treatment and every third day by means of serial measurements of the hepatic artery resistance index (HARI) and the maximum portal vein velocity (PVv) using Doppler ultrasonography in 50 consecutive patients with severe liver diseases admitted to a medical intensive care unit (MICU). The recorded hemodynamic parameters were compared to the MELD score, and the CLIF-C ACLF score to analyze their utility for the prediction of the outcome of patients with severe liver diseases, liver cirrhosis, and ACLF.ResultsThe changes (delta) obtained by serial measurements of the MELD score, HARI, and PVv were analyzed through scatter plots. Bivariate correlation analysis yielded a new positive linear correlation between the delta-HARI and the delta-MELD score (r = 0.469; p < 0.001). In addition, our data revealed a new negative linear correlation between delta-PVv and the delta-MELD score (r = −0.279, p = 0.001). The leading cause of MICU mortality was acute-on-chronic liver failure (ACLF). A subgroup analysis of patients with liver cirrhosis revealed a positive linear correlation between the delta-HARI and the delta-CLIF-C-ACLF score (r = 0.252, p = 0.005). Of clinical relevance, non-survivors of ACLF exhibited a significantly higher mean value for the delta-HARI (0.010 vs. −0.005; p = 0.015) and a lower mean value for the delta-PVv (−0.7 vs. 1.9 cm/s; p = 0.037) in comparison to survivors of ACLF.ConclusionThis study shows the prognostic value of the assessment of hepatic perfusion in critical care patients with severe liver diseases by bedside Doppler ultrasound examination and its utility as an accurate predictor of the outcome in patients with ACLF. Increasing HARI and a decreasing PVv are predictors of an adverse outcome. Delta-HARI and delta-PVv are new biomarkers of prognosis and ACLF-related mortality in patients with liver diseases. Delta-HARI and delta-PVv may be helpful in guiding clinical decision-making, especially in catecholamine and fluid management.

Predicting the Onset of Hepatitis B Virus–Related Acute-on-Chronic Liver Failure

Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome with rapid progression. This study aimed to develop and validate a prognostic score to predict the onset of ACLF in hepatitis B virus (HBV) etiology. The prospective clinical data of 1373 patients with acute deterioration of HBV-related chronic liver disease were used to identify clinical characteristics and develop a prognostic score for the onset of ACLF. Of the patients assessed using the Chinese Group on the Study of Severe Hepatitis B (COSSH)-ACLF criteria, 903 patients with non-ACLF at admission (1 received transplantation at 5 days) were stratified: 71 with progression to ACLF and 831 without progression to ACLF at 7 days. Four predictors (total bilirubin, international normalized ratio, alanine aminotransferase, and ferritin) were associated significantly with ACLF onset at 7 days. The COSSH-onset-ACLF score was constituted as follows: (0.101× ln [alanine aminotransferase]+ 0.819× ln [total bilirubin]+ 2.820× ln [international normalized ratio]+ 0.016× ln [ferritin]). The C-indexes of the new score for 7-/14-/28-day onset (0.928/0.925/0.913) were significantly higher than those of 5 other scores (Chronic Liver Failure Consortium ACLF development score/Model for End-stage Liver Disease score/Model for End-stage Liver Disease sodium score/COSSH-ACLF score/Chronic liver failure Consortium ACLF score; all P < .001). The improvement in predictive errors, time-dependent receiver operating characteristic, probability density function evaluation, and calibration curves of the new score showed the highest predictive value for ACLF onset at 7/14/28 days. Risk stratification of the new score showed 2 strata with high and low risk (≥6.3/<6.3) of ACLF onset. The external validation group further confirmed the earlier results. A new prognostic score based on 4 predictors can accurately predict the 7-/14-/28-day onset of ACLF in patients with acute deterioration of HBV-related chronic liver disease and might be used to guide clinical management.

CD200R Combined Neutrophil-Lymphocyte Ratio Predict 90-Day Mortality in HBV-Related Acute-On-Chronic Liver Failure.

Background: Survival of acute-on-chronic liver failure (ACLF) cannot be properly predicted based on clinical characteristics.Aims: This study aimed to develop a predictive model to evaluating the prognosis for hepatitis B virus-related ACLF (HBV-ACLF) based on specific laboratory and immune indicators.Methods: Baseline laboratory results were obtained and immune indicators were detected by flow cytometry. A predictive model, which estimates the prognosis at 90-day follow-up, was developed using data from a prospective study on 45 patients hospitalized of HBV-ACLF from June 2016 to April 2018 at the Beijing Ditan Hospital, Capital Medical University. The prognostic values of the predictive factors were determined by the area under the receiver operating characteristic (AUROC) curves.Results: Six factors exhibited statistical differences between the survival and non-survival groups: proportions of CD4+TN, CD4+TEM, CD8+TN, CD8+TEM, CD200R+CD4+T cells and neutrophil-lymphocyte ratio (NLR). CD200R combined with the NLR had an AUROC of 0.916, which was significantly higher than the AUROC values of CD200R+CD4+T cells (0.868), NLR (0.761), model for end-stage liver disease (MELD) (0.840), MELD-Na (0.870), Child-Turcotte-Pugh (CTP) (0.580), or chronic liver failure-consortium ACLF (CLIF-C ACLF) score(0.840). At the cut-off point of−3.87, matching the maximum Youden index determined by ROC analysis, the positive predictive and negative predictive values for the mortality were 0.86 and 0.97, respectively.Conclusions: The 90-day prediction model based on baseline levels of CD200R+CD4+T cells and NLR offers potential predictive value for the mortality of HBV-ACLF.

Comparison of General and Liver-Specific Prognostic Scores in Their Ability to Predict Mortality in Cirrhotic Patients Admitted to the Intensive Care Unit.

Introduction Acute Physiology and Chronic Health Evaluation (APACHE) II and III and Sequential Organ Failure Assessment (SOFA) are prognostic scores commonly used in the intensive care unit (ICU). Their accuracy in predicting mortality has not been adequately evaluated in comparison to prognostic scores commonly used in critically ill cirrhotic patients with acute decompensation (AD) or acute-on-chronic liver failure (ACLF). Aims This study was conducted to evaluate the performance of prognostic scores, including APACHE II, SOFA, Chronic Liver Failure Consortium (CLIF-C) SOFA, Child–Turcotte–Pugh (CPS), Model for End-Stage Liver Disease (MELD), MELD-Na, MELD to serum sodium ratio (MESO) index, CLIF-C organ failure (CLIF-C OF), CLIF-C ACLF, and CLIF-C AD scores, in predicting mortality of cirrhotic patients admitted to the ICU. Patients and Methods. A total of 382 patients (280 males, mean age 67.3 ± 10.6 years) with cirrhosis were retrospectively evaluated. All prognostic scores were calculated in the first 24 hours of ICU admission. Their ability to predict mortality was measured using the analysis of the area under the receiver operating characteristic curve (AUC). Results Mortality was observed in 31% of the patients. Analysis of AUC revealed that CLIF-C OF (0.807) and CLIF-SOFA (0.776) had the best ability to predict mortality in all patients, but CLIF-C OF (0.749) had higher prognostic accuracy in patients with ACLF. CLIF-SOFA, SOFA, and CLIF-C AD had the highest AUC values in patients with AD, with no statistical difference (p=0.971). Conclusions When compared to other general or liver-specific prognostic scores, CLIF-C OF, CLIF-SOFA, SOFA, and CLIF-C AD have good accuracy to predict mortality in critically ill patients with cirrhosis and patients with AD. According to the clinical scenario, different scores should be used to provide prognosis to patients with cirrhosis in the ICU.

Serum Clusterin: A Potential Marker for Assessing the Clinical Severity and Short-Term Prognosis of Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.

Background Acute-on-chronic liver failure (ACLF) is a clinical syndrome characterized by acute deterioration of liver function and high short-term mortality. Clusterin, with biological functions similar to small heat shock proteins, can protect cells from apoptosis induced by various stressors. The aim of this study was to detect the level of serum clusterin in hepatitis B virus- (HBV-) related ACLF and to assess the predictive value of clusterin for the short-term prognosis of HBV-ACLF. Methods We detected serum clusterin by ELISA in 108 HBV-ACLF patients, 63 HBV-non-ACLF patients, and 44 normal controls. Results Serum clusterin was markedly lower in HBV-ACLF patients (median, 51.09 μg/mL) than in HBV-non-ACLF patients (median, 188.56 μg/mL) and normal controls (median, 213.45 μg/mL; all P < 0.05). Nonsurviving HBV-ACLF patients who died within 90 days had much lower clusterin levels than did surviving patients, especially those who died within 28 days (nonsurvival group vs. survival group: 39.82 ± 19.34 vs. 72.26 ± 43.52, P < 0.001; survival time ≤ 28 vs. survival time > 28: median 28.39 vs. 43.22, P = 0.013). The results showed that for identifying HBV-ACLF, the sensitivity of clusterin (93.7%) was similar to the sensitivities of the international normalized ratio (INR; 94.4%) and total bilirubin (TBIL; 94.8%), but its specificity (90.7%) was higher than that of prothrombin activity (PTA; 65.8%) and TBIL (69.8%) and was similar to INR (88.9%). As the concentration of clusterin increased, the mortality of HBV-ACLF patients decreased significantly from 59.3% to 7.0%. Clusterin had better ability for predicting the prognosis of HBV-ACLF patients than did the model for end-stage liver disease (MELD) score and the chronic liver failure consortium (CLIF-C) ACLF score (MELD vs. clusterin: P = 0.012; CLIF-C ACLF vs. clusterin: P = 0.031). Conclusion Serum clusterin is a potential biomarker for HBV-ACLF which can be used to assess clinical severity and the short-term prognosis of patients with this disease and may help clinicians identify HBV-ACLF with greater specificity and improved prognostic accuracy than existing prognostic markers.

Strategies for liver transplantation during the SARS-CoV-2 outbreak: Preliminary experience from a single center in France.

Liver transplantation (LT) during the ongoing severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic is challenging given the urgent need to reallocate resources to other areas of patient care. Available guidelines recommend reorganizing transplant care, but data on clinical experience in the context of SARS‐CoV‐2 pandemic are scarce. Thus, we report strategies and preliminary results in LT during the peak of the SARS‐CoV‐2 pandemic from a single center in France. Our strategy to reorganize the transplant program included 4 main steps: optimization of available resources, especially intensive care unit capacity; multidisciplinary risk stratification of LT candidates on the waiting list; implementation of a systematic SARS‐CoV‐2 screening strategy prior to transplantation; and definition of optimal recipient‐donor matching. After implementation of these 4 steps, we performed 10 successful LTs during the peak of the pandemic with a short median intensive care unit stay (2.5 days), benchmark posttransplant morbidity, and no occurrence of SARS‐CoV‐2 infection during follow‐up. From this preliminary experience we conclude that efforts in resource planning, optimal recipient selection, and organ allocation strategy are key to maintain a safe LT activity. Transplant centers should be ready to readapt their practices as the pandemic evolves.

Comparing Eight Prognostic Scores in Predicting Mortality of Patients with Acute-On-Chronic Liver Failure Who Were Admitted to an ICU: A Single-Center Experience.

Limited data is available on long-term outcome predictions for patients with acute-on-chronic liver failure (ACLF) in an intensive care unit (ICU) setting. Assessing the reliability and accuracy of several mortality prediction models for these patients is helpful. Two hundred forty-nine consecutive patients with ACLF and admittance to the liver ICU in a single center in northern Taiwan between December 2012 and March 2015 were enrolled in the study and were tracked until February 2017. Ninety-one patients had chronic hepatitis B-related cirrhosis. Clinical features and laboratory data were collected at or within 24 h of the first ICU admission course. Eight commonly used clinical scores in chronic liver disease were calculated. The primary endpoint was overall survival. Acute physiology and chronic health evaluation (APACHE) III and chronic liver failure consortium (CLIF-C) ACLF scores were significantly superior to other models in predicting overall mortality as determined by time-dependent receiver operating characteristic (ROC) curve analysis (area under the ROC curve (AUROC): 0.817). Subgroup analysis of patients with chronic hepatitis B-related cirrhosis displayed similar results. CLIF-C organ function (OF), CLIF-C ACLF, and APACHE III scores were statistically superior to the mortality probability model III at zero hours (MPM0-III) and the simplified acute physiology (SAP) III scores in predicting 28-day mortality. In conclusion, for 28-day and overall mortality prediction of patients with ACLF admitted to the ICU, APACHE III, CLIF-OF, and CLIF-C ACLF scores might outperform other models. Further prospective study is warranted.

Persistent or incident hyperammonemia is associated with poor outcomes in acute decompensation and acute-on-chronic liver failure.

Background and AimThe effect of elevated ammonia on organ failures (OF), apart from hepatic encephalopathy, in patients with acute decompensation (AD) of cirrhosis and acute‐on‐chronic liver failure (ACLF) is unclear. We aimed to assess the effect of persistent or incident hyperammonemia on OF and outcomes in patients with AD and ACLF.MethodsA total of 229 patients with ACLF and 83 with AD were included. Arterial ammonia was measured on day 1 and day 3 of admission. Persistent or incident hyperammonemia was defined as a level of ≥79.5 μmol/L on day 3. The changes in ammonia levels during the first 3 days were analyzed with respect to the complications and outcomes.ResultsAt admission, the median level of arterial ammonia was higher in ACLF compared to AD patients (103 vs 86 μmol/L, P < 0.001). Persistent or incident hyperammonemia was noted in 206 (66.0%) patients and was more frequent in ACLF compared to AD patients (70.7 vs 53.0%, P = 0.013). Patients with persistent or incident hyperammonemia, compared to those without it, developed a higher proportion of new‐onset OF during hospitalization involving liver (P = 0.018), kidney (P = 0.001), brain (P = 0.005), coagulation (P = 0.036), circulation (P = 0.002), and respiratory (P = 0.003) issues and had higher 28‐day mortality (log‐rank test, P < 0.001). After adjustment for chronic liver failure consortium ACLF score, persistent or incident hyperammonemia (hazard ratio, 3.174) was independently associated with 28‐day mortality. The presence of infection was an independent predictor of persistent or incident hyperammonemia.ConclusionPersistent or incident hyperammonemia during first 3 days of hospitalization in patients with AD or ACLF is associated with increased risk of OF and death.

Acute-on-chronic liver failure: Objective admission and support criteria in the intensive care unit.

SummaryCirrhosis is a leading cause of morbidity and mortality throughout the world. Significant complications include variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, and infection. When these complications are severe, admission to the intensive care unit (ICU) is often required for organ support and management. Intensive care therapy can also serve as a bridge to liver transplantation. Along with decompensation of cirrhosis, the concept of acute-on-chronic liver failure (ACLF) has emerged. This involves an acute precipitating event, such as the development of infection in a patient with cirrhosis, which leads to acute deterioration of hepatic function and extrahepatic organ failure. Extrahepatic complications often include renal, cardiovascular, and respiratory failures. Patients with significant extrahepatic and hepatic failures need ICU admission for organ support. Again, in patients who are deemed suitable liver transplant candidates, intensive care management may allow bridging to liver transplantation. However, patients with a Chronic Liver Failure Consortium ACLF score greater than 70 at 48 to 72 hours post-ICU admission do not seem to benefit from ongoing intensive support and a palliative approach may be more appropriate.

Prognostic utility of novel biomarkers in acute‐on‐chronic liver failure (ACLF) associated with hepatitis B: A multicenter prospective study

Flare-ups of chronic hepatitis B can sometimes be severe and even progress to acute-on-chronic liver failure (ACLF), with high short-term mortality. A timely estimation of the risk of death should be initiated early. The aim of the present study was to determine whether novel biomarkers add prognostic information beyond current clinical scoring systems. Patients with hepatitis B-associated ACLF were prospectively enrolled from five hospitals in China between August 2017 and March 2018. Their plasma was screened for soluble CD163 (sCD163), neutrophil gelatinase-associated lipocalin (NGAL), and copeptin. The association between these biomarkers and mortality was analyzed. The performance of the Model for End-stage Liver Disease, Asian-Pacific Association for the Study of the Liver-ACLF Research Consortium score, and the Chronic Liver Failure Consortium ACLF score, with or without biomarkers, were compared. One hundred fifty one patients were enrolled. Advanced ACLF patients had significantly higher levels than early ACLF individuals of plasma biomarkers sCD163 (P = 0.001), NGAL (P = 0.006), and copeptin (P = 0.049). Thirty-four deaths occurred during the 28-day follow-up period (22.5%). Both sCD163 and NGAL showed a strong independent association with 28-day mortality, whereas copeptin did not. Scoring systems incorporating sCD163 and NGAL had better discrimination and calibration, as measured by area under the receiver operating characteristic curves, the Akaike information criteria, integrated discrimination improvement, and net reclassification improvement. Soluble CD163 and NGAL are independently associated with short-term mortality in hepatitis B-associated ACLF. Use of a combination of sCD163 and NGAL improves prognostication.

Applicability of Liver Transplantation for Patients with Acute on Chronic Liver Failure

Liver transplantation (LT) for acute on chronic liver failure (ACLF) may become the only chance to survive when other therapeutic measures fail. However, to reach a LT in this condition is difficult given its high short term mortality. Prevalence rates were reported between 24 to 34%.This data has not been described in our population Aim: to evaluate the prevalence and outcome of ACLF patients (pts) listed in our LT unit. Patients and Methods: Adults pts with chronic liver disease that were consecutive listed for LT between Jan/15 and Jun/16 were included and divided in two groups: ACLF and Non-ACLF. Age, gender, etiology of liver disease, presence of hepatocellular carcinoma, comorbid conditions, Child-Pugh and MELD, and pre and post LT outcome were compared on both groups. The chronic liver failure (CLIF) Consortium Organ Failure Score was used in the diagnosis and grading of ACLF, and the CLIF Consortium ACLF score (CLIF-C ACLF) was used to estimate probability of dying Results Prevalence of ACLF was 15%, 13 of 86 pts fulfilled ACLF criteria, 4 at the time of inclusion in the waiting list and 9 after 52 (13-360) days Precipitating events were bacterial infection (31%), gastrointestinal bleeding (15%), active alcoholism (8%), hemoperitoneum (8%) and non identified in the remaining 38%. Resolution of ACLF, access to LT or death for ACLF grade 1 (n=6) were 33%/50%/17%, for grade 2 (n=2) 0%,50%,100% and for grade 3 (n=5) 0%, 0%,100% respectively. The real waiting list mortality and the predicted by CLIF-C ACLF on ACLF pts at 28 days were 36%/42% and at 90 days 62%/56% (p=NS). Post-LT survival for non-ACLF/ACLF pts at 28, 90 and 180 days were 96%/75%, 92%/75% and 88%/75% (p=NS) Conclusions 1)Patients with ACLF grade 1 had the higher chance of resolution and / or transplantation 2) CLIF-C ACLF had a good correlation with the mortality found in this study 3) Post-LT survival was lower in pts with ACLF compared to non- ACLF, however, this difference was not statistically significant 4)More studies are required to define criteria to prioritize or reject the inclusion in the list of patients, according to the degree of ACLF

Elevated cardiac troponin T in cirrhotic patients with emergency care admissions: Associations with mortality.

Mortality of cirrhotic patients after emergency care admission is high, and prognostic factors can help in prioritizing patients. The aim of our study was to assess the association between levels of cardiac troponin T (cTnT) and 1-year mortality in patients with liver cirrhosis without known cardiac disease, who were admitted to the emergency department (ED). All patients with cirrhosis presented to the ED from October 2009 until August 2015 who had an initial cTnT value measured with the first lab panel were retrospectively analyzed with a follow-up of 365days. Of a total of 237 cirrhotic ED patients, cTnT measurements were available for 87 (63% men, mean age 58.9±11.0years, and median Model for End-stage Liver Disease score was 15 [25th-75th percentile: 10-19]). Chronic Liver Failure Consortium acute-on-chronic liver failure (CLIF-C-ACLF) score was 33. Forty-three patients (49%) had cTnT values above the normal range (14ng/L), of which 19 (22%) had values over 30ng/L. Two patients were lost to follow-up. In multivariable analysis, both CLIF-C-ACLF (hazard ratio 1.072 per point increase; 95% confidence interval 1.029-1.117; P<0.001) and cTnT (hazard ratio 1.014 per ng/L increase; 95% confidence interval 1.004-1.024; P=0.008) emerged as independently associated with mortality. A large proportion of cirrhotic patients in the ED have elevated levels of cTnT even if there is no evidence of cardiac disease. Elevated cTnT is associated with increased mortality during 1year after correcting for Model for End-stage Liver Disease and CLIF-C-ACLF scores.

Single center validation of mortality scores in patients with acute decompensation of cirrhosis with and without acute-on-chronic liver failure

Objectives: Acute decompensation (AD) of cirrhosis is characterized by high mortality. We aimed to validate the performance in predicting mortality of both the chronic-liver-failure-consortium (CLIF-C) acute-on-chronic liver failure (ACLF) and CLIF-C AD scores in a cohort of patients admitted for AD.Methods: In this prospective cohort study, patients were followed-up during their hospital stay and for 365 days thereafter.Results: About 182 patients with AD were enrolled including 78 (42.8%) who met the criteria for ACLF (ACLF-group) while the remaining had AD without ACLF (AD-group). 56.4% and 56.7% of the ACLF- and AD-groups, respectively, had alcoholic cirrhosis and 85.9% of the ACLF-group hepatic encephalopathy. Only few patients were hospitalized in the intensive care unit (ICU) or transplanted. The probabilities of death estimated for both scores were similar to the overall mortality rates observed at all time points. The model had a good fit in the AD-group at 90 days (p = .974) but a worse, yet adequate, in the ACLF-group at 28 days (p = .08). The CLIF-C ACLF or AD scores had an adequate, predictive discrimination ability for mortality at all time points, with Harrel’s concordance index-C ranging between 0.64 and 0.65 or 0.64 and 0.68, respectively. Both scores showed a similar predictive accuracy for mortality compared to those of MELD, MELD-Na and Child-Pugh.Conclusions: In this population without access to appropriate ICU treatment, the CLIF-C ACLF and AD performed worse than in studies with patients having ICU access. In addition, the CLIF scores were not superior to classical ones in this setting.