CLIF-C Acute-on-chronic Liver Failure Research Articles

Hepatocytic Apoptosis and Immune Dysfunction in Decompensation of Alcoholic Liver Cirrhosis with Different Grades of Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) of varying grades was assessed in 110 patients with alcoholic liver cirrhosis using the on-line CLIF-C ACLF Calculator ( www.efclif.com/scientific-activity/score-calculators/clif-c-aclf ); fragments of cytokeratin-18, TNFα, IL-1β, IL-4, IL-6, and IL-8 were also assayed. As ACLF progressed from grade 0 to grade 3, the levels of cytokeratin-18 fragments, IL-6, and IL-8 significantly increased, while IL-4 decreased. TNFα peaked in ACLF grade 1, but decreased in grades 2 and 3. IL-1β did not depend on the ACLF grade. Thus, hepatic damage and immune dysfunction are implicated in the progression of ACLF.

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.

From the Editor’s desk…

From the Editor’s desk…

P-36 ACCURACY OF PROGNOSTIC SCORES IN PREDICTION OF MORTALITY IN CIRRHOTIC PATIENTS ADMITTED TO THE INTENSIVE CARE UNIT

SAPS-3 and SOFA are prognostic scores commonly employed in intensive care unit (ICU). Their accuracy in prediction of mortality has not been adequately evaluated in comparison to prognostic scores commonly employed cirrhotic patients with acute decompensation (AD) or acute-on-chronic liver failure (ACLF). To evaluate the performance of prognostic scores, including SAPS-3, SOFA, CLIF-SOFA, Child-Pugh (CPS), MELD, MELD-Na, CLIF-C organ failure, CLIF-C ACLF, CLIF-C AD scores in the prediction of mortality in unselected patients with cirrhosis admitted to the ICU. 213 (150 males, median age 67 [31-91] years) with cirrhosis admitted to the ICU were retrospectively evaluated. All prognostic scores were calculated in the first 24 hours of admission. Their ability to predict mortality was measured using receiver operating characteristic (ROC) curve. Mortality was observed in 42% of the patients. Analysis of ROC curves revealed that SOFA (0,88) had the best ability to predict mortality, when compared to MELD-Na (0,76), MELD (0,75), CPS (0,71) and SAPS 3 (0,51). In those patients with ACLF, CLIF-ACLF (0,74), CLIF-OF (0,70), MELD-Na (0,73) and MELD (0,69) had a better performance, when compared to SAPS 3 (0,55), SOFA (0,63) and CLIF-SOFA (0,66). When compared to other general or liver-specific prognostic scores, CLIF-ACLF and SOFA have a better accuracy to predict mortality, respectively, in patients with and without ACLF. SAPS 3 should not be employed as a prognostic score in critically-ill cirrhotic patients.

Role of Bacterial Infection in the Development of Acute Liver Failure in Patients with Decompensated Alcoholic Liver Cirrhosis.

We examined 74 patients with acute decompensation of alcoholic liver cirrhosis: 34 (45.9%) with bacterial infection (group 1) and 40 (54.1%) without bacterial infection (group 2). The degree and index of acute-on-chronic liver failure (ACLF) were determined using an on-line CLIF-C ACLF Calculator and the levels of cytokeratin-18 fragments, TNFα, IL-1β, IL-4, IL-6, and IL-8. In group 1, AST, cytokeratin-18, TNFα, IL-1β, IL-6, degree and score of ACLF were significantly higher than in group 2. ACLF developed in 18 (52.9%) patients in group 1 and in 11 (27.5%) (p<0.05) patients in group 2. Within 1 month, 10 (29.4%) patients of group 1 and 2 (5%) patients of group 2 died (p<0.05). Patients with bacterial infection showed a more severe course of alcoholic liver cirrhosis and ACLF than those without bacterial infection.

Acute-on-chronic liver failure: Where do we stand?

Acute-on-chronic liver failure (ACLF) is defined by the rapid development of organ(s) failure(s) associated with high rates of early (28-day) mortality in patients with cirrhosis. ACLF has been categorized into three grades of increasing severity according to the nature and number of organ failures. In patients with grade 3 ACLF, 28-day mortality is >70%. While the definition of ACLF has been endorsed by European scientific societies, North American and Asian Pacific associations have proposed alternative definitions. A prognostic score called the CLIF-C ACLF score provides a more precise assessment of the prognosis of patients with ACLF. Although bacterial infections and variceal bleeding are common precipitating factors, no precipitating factor can be identified in almost 60% of patients with ACLF. There is increasing evidence that cirrhosis is a condition characterized by a systemic inflammatory state and occult infections or translocation of bacteria or bacterial products from the lumen of the GUT to the systemic circulation which could play a role in the development of ACLF. Simple and readily available variables to predict the occurrence of ACLF in patients with cirrhosis have been identified and high-risk patients need careful management. Whether prolonged administration of statins, rifaximin or albumin can prevent ACLF requires further study. Patients with organ(s) failure(s) may needed to be admitted to the ICU and there should be no hesitation in admitting patients with cirrhosis to the ICU. No benefit to survival was observed with albumin dialysis and rescue transplantation is the best option in the most severe patients. One-year post-transplant survival rates exceeding 70%-75% have been reported, including in patients with grade 3 ACLF but these patients were highly selected. Criteria have been proposed to define futile transplantation (too ill to be transplanted), but these criteria need to be refined to include age, comorbidities and frailty in addition to markers of disease severity.

Evaluation of prognostic value of neutrophil-to-lymphocyte ratio in patients with acute-on-chronic liver failure or severe liver injury from chronic HBV infection.

Acute-on-chronic liver failure (ACLF) is associated with bacterial infection and poor outcome. Neutrophil-to-lymphocyte ratio (NLR) is used to assess bacterial infection and immune dysfunction in numerous diseases. We aimed to evaluate NLR as a prognostic biomarker and to explore its combination with accepted prognostic models in ACLF patients. This retrospective study included patients with ACLF or severe liver injury from chronic HBV infection admitted to three tertiary academic hospitals in China from 2013 to 2019. Baseline NLR was correlated with ACLF grade, bacterial infection, survival and accepted ACLF scores. Baseline NLR values were significantly increased in nonsurvivors and patients with bacterial infection at or after admission and were unaffected by cirrhotic status in 412 transplant-free patients included in three cohorts. Compared with accepted scores, NLR showed moderate accuracy in predicting 28-day mortality and high accuracy in predicting 90-day mortality. Three levels of mortality risk were graded on the basis of NLR values (<3.10, 3.10-4.79 and >4.79), and NLR >4.79 was associated with 53.2-60.0% 28-day and 75.0-80.0% 90-day mortality in these cohorts. Multivariate analyses indicated that NLR retained statistical significance independently of CLIF consortium organ failure score (CLIF-C OFs). NLR-based CLIF-C ACLF score was primarily developed and showed excellent performance in predicting 28/90-day mortality. NLR is a dependable biomarker for bacterial infection assessment and short-term mortality prediction in ACLF patients and can be used jointly with CLIF-C OFs to improve the accuracy of mortality prediction in patients with the disease. NLR-based CLIF-C ACLF model needs further validation.

Applicability and safety of discontinuous ADVanced Organ Support (ADVOS) in the treatment of patients with acute-on-chronic liver failure (ACLF) outside of intensive care

ADVanced Organ Support (ADVOS) is a novel type of extracorporeal albumin dialysis and holds promise to sustain liver function and recovery of patients with acute-on-chronic liver failure (ACLF). Previously, ADVOS was tested as continuous treatment for intensive care patients with liver failure. Data related to the applicability and safety as discontinuous treatment outside of ICU is not available. Evaluation of ADVOS as discontinuous treatment for patients with ACLF outside intensive care unit and comparison with a matched historic cohort. In this retrospective study, 26 patients with ACLF and the indication for renal replacement therapy related to HRS-AKI were included. Majority of patients were male (65%) with alcoholic cirrhosis in 88% and infections as a trigger of ACLF in 96%. Liver function was severely compromised reflected by high median MELD and CLIF-C ACLF scores of 37 (IQR 32;40) and 56.5 (IQR 51;60), respectively. Patients were treated discontinuously with ADVOS over a median time of 12 days (IQR 8.25;17) and received 8 (IQR 4.25;9.75) treatment cycles on average. No treatment related adverse events were recorded, and safety laboratory parameters remained constant during the observation time. After 16 h cumulative dialysis therapy, ADVOS significantly reduced protein-bound bilirubin (14%), creatinine (11.8%) and blood urea nitrogen (BUN, 33%). Using a matched cohort with ACLF treated with hemodialysis, ADVOS achieved a stronger decrease in bilirubin (p = 0.01), while detoxification of water-soluble catabolites' including creatinine and BUN was comparable. The 28-days mortality in the ADVOS group was 56% (14/26) and was not inferior to predicted survival (predicted median 28-days mortality was 44%, IQR 30; 59). Discontinuous ADVOS treatment was safe and effective in patients with ACLF outside intensive care and outperformed hemodialysis in reducing protein-bound metabolites.

Comparing CLIF-C ACLF, CLIF-C ACLFlactate, and CLIF-C ACLF-D Prognostic Scores in Acute-on-Chronic Liver Failure Patients by a Single-Center ICU Experience.

Patients with liver cirrhosis have a higher risk of developing acute-on-chronic liver failure (ACLF). Poor prognosis with a high rate of short-term mortality leads to limited opportunities for further liver transplantation. Thus, precise prognostic evaluation of patients with ACLF is necessary before transplant surgery. In this study, a total of one hundred and thirty-five patients with ACLF admitted to the hepato-gastroenterologic intensive care unit (ICU) for intensive monitoring and treatment at Chang-Gung Memorial Hospital (CGMH, Linkou, Taiwan) were screened from November 2012 to April 2015 and tracked until April 2017. Three new prognostic scores of ACLF, including CLIF-C ACLF (Chronic Liver Failure Consortium Acute-on-chronic Liver Failure score), CLIF-C ACLF-D (CLIF-C ACLF Development score), and CLLF-C ACLFlactate (lactate-adjusted CLIF-C ACLF score) were compared. The primary outcome considered was overall mortality. Mortality predictions at 28, 90, 180, and 365 days were also calculated. By area under the receiver operating characteristic curve (AUROC) analysis, the CLIF-C ACLF and CLIF-C ACLF-D scores were superior to CLIF-C ACLFlactate scores in predicting 28-day mortality. The CLIF-C ACLF-D score had the highest AUROC in predicting overall mortality as well as at 90, 180, and 365 days. In conclusion, our study demonstrates that CLIF-C ACLF and CLIF-C ACLF-D scores are significant predictors of outcome in critical patients with liver cirrhosis and ACLF. The CLIF-C ACLF-D score may have a superior predictive power for the prediction of 3-month, 6-month, and one-year mortality.

Characteristics and outcomes of acute-on-chronic liver failure patients with or without cirrhosis using two criteria

The aim of the study was to identify the characteristics and outcomes in acute-on-chronic liver failure (ACLF) patients with or without cirrhosis using two criteria. Patients with acute deterioration of chronic hepatic disease or acute decompensation of cirrhosis were included retrospectively from April 10, 2016 to April 10, 2019. European Association for the Study of the Liver-chronic liver failure (EASL-CLIF) criterion except for consideration of cirrhosis and Chinese Group on the Study of Severe Hepatitis B (COSSH) criterion were used. Clinical features, laboratory data and survival curves were compared between the ACLF patients with and without cirrhosis. A total of 799 patients were included. Among them, 328 had COSSH and EASL ACLF, 197 had COSSH alone, and 104 had EASL alone. There were 11.6% more ACLF with COSSH criterion. Furthermore, EASL ACLF patients with non-cirrhosis vs. cirrhosis had different laboratory characteristics: ALT (423 vs. 154, p < 0.001), AST (303 vs. 157, p < 0.001), γ-GT (86 vs. 75, p < 0.01), and INR (2.7 vs. 2.6, p < 0.001) were significantly higher but creatinine (71 vs. 77, p < 0.01) were significantly lower; but importantly there was no statistical changes between non-cirrhosis and cirrhosis in EASL ACLF patients on 28-day (p = 0.398) and 90-day (p = 0.376) survival curves. However, 90-day (p = 0.030) survival curve was different between non-cirrhosis and cirrhosis in COSSH ACLF patients. COSSH ACLF score (auROC = 0.778 or 0.792, 95%CI 0.706–0.839 or 0.721–0.851) displayed the better prognostic ability for EASL ACLF patients with non-cirrhosis, but CLIF-C ACLF score (auROC = 0.757 or 0.796, 95%CI 0.701–0.807 or 0.743–0.843) still was the best prognostic scoring system in EASL ACLF patients with cirrhosis. In conclusions, EASL definition exhibited better performance on homogeneous identification of ACLF regardless of cirrhosis or non-cirrhosis. And COSSH ACLF score displayed the better prognostic ability for EASL ACLF patients without cirrhosis.

Comparison of CLIF-C ACLF Score and MELD Score in Predicting ICU Mortality in Patients with Acute-On-Chronic Liver Failure.

IntroductionAcute-on-chronic liver failure (ACLF) is a serious complication of liver cirrhosis which presents with hepatic and/or extrahepatic organ failure and often needs admission to an Intensive Care Unit (ICU). This condition typically needs organ support and carries a high mortality rate. ICU care may not benefit these patients. There are many scores to assess prognosis in these patients, such as the Model for End-stage Liver Disease (MELD) score, the MELD score refined to take into account serum sodium level (MELD-Na), the chronic liver failure organ failure (CLIF-OF) score, the CLIF Consortium acute-on-chronic liver failure (CLIF-C ACLF) score and the Child-Turcotte-Pugh classification. This study was conducted to compare CLIF-C ACLF and MELD scores for selecting patients at risk of high mortality, as ICU care to these patients in the absence of liver transplantation may be of no value.MethodsThe data of 75 patients admitted to the ICU of Shifa International Hospital in Islamabad were prospectively analyzed. CLIF-C ACLF and MELD scores were calculated at admission and then at 24 and 48 hours after the ICU stay. Data were analyzed with the assistance of SPSS. Mortality was the primary outcome.ResultsComparison of both scores showed that a CLIF-C ACLF score ≥ 70 at 48 hours predicts mortality more accurately, with an area under receiver operating curve (AUROC) of 0.643 (confidence interval [CI] 95% 0.505-0.781; p=0.046) which was significantly higher than MELD scores of 30,40 and 50 at 48 hours. Organ failure and the need for supportive care were strong predictors of mortality (p= < 0.05).ConclusionWe concluded that a CLIF-C ACLF score ≥ 70 at 48 hours and organ failure are better predictors of mortality and that ICU care in these patients does not benefit them. Definitive therapy in the form of liver transplantation may have a promising role, if considered early.

Noninvasive models for predicting poor prognosis of chronic HBV infection patients precipitating acute HEV infection

Hepatitis E virus (HEV) infection contributes to a considerable proportion of acute-on-chronic liver failure (ACLF) in patients with chronic hepatitis B virus (HBV) infection. This study aimed to predict the prognosis of chronic HBV infection patients precipitating acute HEV infection. A total of 193 patients were enrolled in this study. The performances of three chronic liver disease prognostic models (CTP score, MELD score, and CLIF-C ADs) were analyzed for predicting the development of ACLF following HEV superimposing chronic HBV infection. Subsequently, the performances of five ACLF prognostic assessment models (CTP score, MELD score, CLIF-C ACLFs, CLIF-C OFs, and COSSH-ACLFs) were analyzed for predicting the outcome of those ACLF patients. Of 193 chronic HBV infection patients precipitating acute HEV infection, 13 patients were diagnosed ACLF on admission, 54 patients developed to ACLF after admission, and 126 patients had non-ACLF during the stay in hospital. For predicting the development of ACLF, CTP score yielded a significantly higher AUROC compared with MELD score and CLIF-C ADs (0.92, 0.88, and 0.86, respectively; all p < 0.05). For predicting the poor prognosis of ACLF patients, the COSSH-ACLFs yielded a significantly higher AUROC compared with CLIF-C ACLFs, CLIF-C OFs, MELD score, and CTP score (0.89, 0.83, 0.81, 0.67, and 0.58, respectively; all p < 0.05). In conclusion, the stepwise application of CTP score and COSSH-ACLFs can predict the prognosis of chronic HBV infection patients precipitating acute HEV infection.

Acute-on-chronic liver failure: a single-centre experience.

Aim of the studyWe set out to determine the applicability of acute-on-chronic liver failure (ACLF) diagnostic criteria and characteristics of thus defined ACLF sub-cohorts in a real-life clinical context.Material and methodsRetrospective charts’ analysis of consecutive patients hospitalized with decompensated liver disease. Inclusion criteria: acute decompensation, informed consent. Exclusion criteria: malignancy. Diagnostic tools: 1st phase – CLIF-SOFA score calculated manually; 2nd phase – CLIF-C ACLF score calculated at www.efclif.com.ResultsOf 432 hospitalized patients aged 52 years, 41% were female, with MELD 20, 32% patients had acute decompensation (AD); main triggers were alcoholic hepatitis (38%), infections (26%), and variceal bleeding (23%). Of patients with AD, ACLF grades 0-3 was present in 64%, 19%, 13%, and 4%, respectively. In hospital mortality according to final AD/ACLF grade in ACLF 0-3 was 7.5%, 42%, 47%, and 80%, respectively (p < 0.0001).ConclusionsDiagnosing ACLF is nowadays easy; it helps to stratify patients at admission, and refine risk stratification at day 7. The main trigger of AD/ACLF in this region is alcohol. Currently, there are no ACLF-specific treatments; however, timely intensive supportive care can influence the prognosis. Even though still elusive and controversial, the ACLF concept can help systematize management of patients admitted with acute decompensation of advanced chronic liver disease.

1119 Assessment of Utility of Prognostic Models for Predicting Short-Term Mortality of Patients With Acute-on-Chronic Liver Failure

INTRODUCTION: Acute-on-chronic liver failure (ACLF) is a clinical syndrome associated with high short-term mortality. Numerous models have been proposed to predict outcomes in ACLF patients, including novel ones by Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC), but their utility in a heterogeneous population of ACLF patients remains inconclusive. The study aims to assess the performance of established and newer models for predicting mortality of ACLF patients. METHODS: A retrospective study of 96 patients fulfilling either APASL or European Association for the Study of the Liver (EASL) criteria for ACLF admitted to a tertiary hospital in Singapore between 2004 and 2018 was performed. Child-Turcotte-Pugh (CTP) score, Model for End-Stage Liver Disease (MELD)-Na, Chronic Liver Failure Consortium (CLIF)-SOFA, CLIF-C ACLF and AARC prognostic scores (MELD-lactate, AARC-ACLF) were calculated on days 1, 4, 7 of hospital admission and days 1, 4 of ICU admission. Outcomes assessed were survival to discharge without transplant, 30-day survival and 90-day survival. The scores were evaluated by measuring area under receiver operating characteristic (AUROC) curve at each time point and compared. RESULTS: 28 patients (29.2%) survived to discharge without transplant, 21 patients (21.9%) underwent urgent transplant and 47 patients (49%) died before discharge. 30-day transplant-free survival was 21.9% and 90-day survival was 19.8%. CTP, MELD-Na, MELD-lactate, CLIF-C ACLF and AARC-ACLF scores had high accuracy in predicting hospital mortality on day 4 admission (CTP D1 AUROC 0.642, D4 0.715; MELD-Na D1 0.607, D4 0.721; MELD-lactate D1 0.664, D4 0.861; CLIF-C ACLF D1 0.559, D4 0.697; AARC-ACLF D1 0.571, D4 0.747). CTP, MELD-Na and MELD-lactate scores also had good predictive utility on day 7 admission (CTP D7 0.684; MELD-Na 0.67; MELD-lactate 0.848). This held true regardless of whether APASL or EASL criteria was applied. In addition, the sequential change in CLIF-SOFA and CLIF-C ACLF scores from day 1 to day 4 was significantly associated with need for urgent transplant or death before discharge. CONCLUSION: CTP, MELD-Na and MELD-lactate scores are superior at prognosticating outcomes on day 4 and 7 of admission in our multi-ethnic Asian population. The trend of CLIF-SOFA and CLIF-C ACLF scores from day 1 to day 4 of admission may also contribute valuable information to our assessment of ACLF patients.

Intermittent high‐flux albumin dialysis with continuous venovenous hemodialysis for acute‐on‐chronic liver failure and acute kidney injury

Acute-on-chronic liver failure (ACLF) requiring intensive medical care and associated with acute kidney injury (AKI) has a mortality rate as high as 90% due to the lack of effective therapies. In this study, we assessed the effects of intermittent high-flux single-pass albumin dialysis (SPAD) coupled with continuous venovenous hemodialysis (CVVHD) on 28-day and 90-day survival and an array of clinical and laboratory parameters in patients with severe ACLF and renal insufficiency. Sixteen patients were studied. The diagnosis of ACLF and AKI was made in accordance with current EASL Clinical Practice Guidelines, including the recommendations of the International Club of Ascites. All patients received SPAD/CVVHD treatments as the blood purification therapy to support liver, kidneys, and other organs. Five patients were transplanted and 11 were not listed for transplantation because of active alcoholism. Data at the initiation of SPAD/CVVHD were compared with early morning data after the termination of the extracorporeal treatment phase. All patients had ACLF and renal insufficiency with 13/16 additionally fulfilling the AKI criteria. A total of 37 SPAD/CVVHD treatments were performed [2.3±1.4]. The baseline MELD-Na score was 37.6±6.6 and decreased to 33.4±8.7 after SPAD/CVVHD (P<0.001). In parallel, the CLIF-C ACLF grade and OF score, estimated at 28- and 90-day mortality, AKI stage, hepatic encephalopathy grade, and liver function tests were lowered (P=0.001-0.032). The 28- and 90-day survivals were 56.2% overall and 53.8% in AKI. Survival in patients not transplanted (n=11) was 45.4%. In patients with severe ACLF and AKI, the renal replacement therapy coupled with high-performance albumin dialysis improved estimated 28- and 90-day survival and several key clinical and laboratory parameters. It is postulated that these results may be further improved with earlier intervention and more SPAD treatments per patient. High-performance albumin dialysis improves survival and key clinical and laboratory parameters in severe ACLF and AKI.

The Role of the CLIF-C OF and the 2016 MELD in Prognosis of Cirrhosis with and without Acute-on-Chronic Liver Failure

Introduction and aim. Acute-on-chronic liver failure (ACLF) is defined by the development of acute deterioration of liver function associated with failure of other organs and high short-term mortality in patients with chronic liver disease (CLD). There is no consensus on the diagnostic criteria, and its independence from ordinary decompensation of CLD has frequently been questioned. This study aimed to identify and characterize this condition and to test the CLIF-C OF score comparing it to the 2016-MELD (with sodium) and the Child-Pugh.Material and methods. 18-month prospective observational study with systematic inclusion of admitted patients with CLD decompensation.Results. 39 patients had ACLF (33.1%). These patients experienced higher 28-day and 90-day mortality, when compared to patients without ACLF (43.6% and 64.1% vs. 2.5% and 7.6% respectively, p < 0.0001). ACLF was linked with a higher acute infection rate (74.4%). For all patients (N = 118), the scores 2016-MELD, CLIF-C OF and Child-Pugh showed an area under the curve (AUC) for 28-day mortality of 0.908, 0.844, 0.753 and for 90-day of 0.902, 0.814, 0.724 respectively, p < 0.0001 for all scores. The 90-day mortality 2016-MELD AUC was greater than the CLIF-C OF AUC, p = 0.021. Within ACLF patients, the 2016-MELD, CLIF-C ACLF and Child-Pugh scores showed an AUC of 0.774, 0.734, 0.584 (28-day) and 0.880, 0.771, 0.603 (90-day); for 2016-MELD p = 0.004 (28-day) and p < 0.0001 (90-day).Conclusion. ACLF is a frequent and relevant condition, associated with high mortality. The CLIF-C OF score revealed good accuracy and diagnoses ACLF when it is present. However, the 2016-MELD performed better for 90-day mortality prediction.

Lactate Improves Prediction of Short‐Term Mortality in Critically Ill Patients With Cirrhosis

Lactate levels and lactate clearance are known predictors of outcome in critically ill patients in the intensive care unit (ICU). The prognostic value of lactate is not well established in liver cirrhosis and acute-on-chronic liver failure (ACLF). The aim of this study was to assess the prognostic value of lactate levels and clearance in critically ill patients with cirrhosis. Patients with cirrhosis admitted to the ICU were studied at the University Medical Center Hamburg-Eppendorf (n = 566, derivation cohort) and the Medical University of Vienna and the University Hospitals Leuven (n = 250, validation cohort). Arterial lactate was measured on admission and during the first 24 hours. Patients were followed for 1 year and outcome was assessed. Admission lactate was directly related to the number of organs failing and to 28-day mortality (area under receiver operating characteristic [AUROC] 0.72; P < 0.001). This also applied to lactate follow-up measurements after 6, 12, and 24 hours (P < 0.001 for all, AUROC > 0.70 for all). Lactate clearance had significant predictive ability for 28-day mortality in patients with elevated serum lactate ≥5 mmol/L. Admission lactate and 12-hour lactate clearance (in patients with admission lactate ≥5 mmol/L), respectively, were identified as significant predictors of 1-year mortality, independent of Chronic Liver Failure Consortium acute-on-chronic liver failure score (CLIF-C ACLFs). A lactate-adjusted CLIF-C ACLFs was developed (CLIF-C ACLFsLact ), which performed significantly better than the original CLIF-C ACLFs in prediction of 28-day mortality in the derivation and validation cohort. Conclusion: Lactate levels appropriately reflect severity of disease and organ failure and were independently associated with short-term mortality in critically ill patients with liver cirrhosis. Lactate is a simple but accurate prognostic marker, and its incorporation improved performance of CLIF-C ACLFs significantly.

Invasive fungal infections amongst patients with acute-on-chronic liver failure at high risk for fungal infections.

To study the prevalence, risk factors, role of serum biomarkers for diagnosis and impact of invasive fungal infections (IFIs) in patients with acute-on-chronic liver failure (ACLF). An analysis of IFI in patients with ACLF (EASL criteria) was conducted retrospectively. The diagnosis of IFI in clinically suspected patients was based on EORTC/MSG criteria. The demographical, clinical, laboratory details and outcomes were analysed. Out of 264 patients with ACLF, 54 (20.4%) patients with suspicion of IFI were evaluated and IFI was diagnosed in 39 (14.7%). Invasive candidiasis was documented in 25 (64.1%) and invasive aspergillosis in 14 (35.8%). The most common source of infection was respiratory (n=13) followed by renal (n=7) and spontaneous fungal peritonitis (n=6). On univariate analysis, diabetes mellitus, hemodialysis, prior antibiotic use, cerebral and respiratory organ failures, Chronic Liver Failure Consortium (CLIF-OF and CLIF-C ACLF) scores were predictors for development of IFI (P<0.05). On multivariate analysis, hemodialysis and prior antibiotics use predicted the development of IFI (P<0.05). Non-survivors were more likely to have IFI (P=0.029), high CLIF-OF and CLIF-C ACLF scores (P<0.001; for both) and higher 1,3-β D Glucan (BDG) levels (P=0.009). The sensitivity, specificity, and AUROC of BDG (80pg/mL) and Galactomannan index (GMI [0.5]) for diagnosing IFI were 97.4%, 60%, 0.770% and 43.6%, 100%, 0.745 respectively. Invasive fungal infections constitutes an important cause of mortality in ACLF patients. BDG and GMI can be useful markers to guide antifungal therapy in patients at high risk for IFI.

Nomogram prediction of individual prognosis of patients with acute-on-chronic hepatitis B liver failure

BackgroundThe current definitions and etiologies of acute-on-chronic liver failure (ACLF) are clearly very different between East and West. AimsThis study aimed to develop an effective prognostic nomogram for acute-on-chronic hepatitis B liver failure (ACHBLF) as defined by the Asia Pacific Association for the Study of the Liver (APASL). MethodsThe nomogram was based on a retrospective study of 573 patients with ACHBLF, defined according to the APASL, at the Beijing Ditan Hospital. The results were validated using a bootstrapped approach to correct for bias in two external cohorts, including an APASL ACHBLF cohort (10 hospitals, N = 329) and an EASL-CLIF ACHBLF cohort (Renji Hospital, N = 300). ResultsMultivariate analysis of the derivation cohort for survival analysis helped identify the independent factors as age, total bilirubin, albumin, international normalized ratio, and hepatic encephalopathy, which were included in the nomogram. The predictive value of nomogram was the strongest compared with CLIF-C ACLF, MELD and MELD-Na and similar to COSSH-ACLF in both the derivation and prospective validation cohorts with APASL ACHBLF, but the CLIF-C ACLF was better in the EASL-CLIF ACHBLF cohort. ConclusionsThe proposed nomogram could accurately estimate individualized risk for the short-term mortality of patients with ACHBLF as defined by APASL.

The Role of the CLIF-C OF and the 2016 MELD in Prognosis of Cirrhosis with and without Acute-on-Chronic Liver Failure

Introduction and aim. Acute-on-chronic liver failure (ACLF) is defined by the development of acute deterioration of liver function associated with failure of other organs and high short-term mortality in patients with chronic liver disease (CLD). There is no consensus on the diagnostic criteria, and its independence from ordinary decompensation of CLD has frequently been questioned. This study aimed to identify and characterize this condition and to test the CLIF-C OF score comparing it to the 2016-MELD (with sodium) and the Child-Pugh. Material and methods. 18-month prospective observational study with systematic inclusion of admitted patients with CLD decompensation. Results. 39 patients had ACLF (33.1%). These patients experienced higher 28-day and 90-day mortality, when compared to patients without ACLF (43.6% and 64.1% vs. 2.5% and 7.6% respectively, p &lt; 0.0001). ACLF was linked with a higher acute infection rate (74.4%). For all patients (N = 118), the scores 2016-MELD, CLIF-C OF and Child-Pugh showed an area under the curve (AUC) for 28-day mortality of 0.908, 0.844, 0.753 and for 90-day of 0.902, 0.814, 0.724 respectively, p &lt; 0.0001 for all scores. The 90-day mortality 2016-MELD AUC was greater than the CLIF-C OF AUC, p = 0.021. Within ACLF patients, the 2016-MELD, CLIF-C ACLF and Child-Pugh scores showed an AUC of 0.774, 0.734, 0.584 (28-day) and 0.880, 0.771, 0.603 (90-day); for 2016-MELD p = 0.004 (28-day) and p &lt; 0.0001 (90-day). Conclusion. ACLF is a frequent and relevant condition, associated with high mortality. The CLIF-C OF score revealed good accuracy and diagnoses ACLF when it is present. However, the 2016-MELD performed better for 90-day mortality prediction.