Acute-on-chronic Liver Failure Score Research Articles

Therapeutic plasma-exchange improves short-term, but not long-term, outcomes in patients with acute-on-chronic liver failure: A propensity score-matched analysis.

Acute-on-chronic liver failure (ACLF) is associated with a high short-term mortality rate in the absence of liver transplantation. The role of therapeutic plasma exchange (TPE) in improving the outcomes of ACLF and acute decompensation (AD) is unclear. In this retrospective analysis, we aimed to determine the impact of TPE on mortality in patients with ACLF. ACLF patients receiving TPE with standard medical treatment (SMT) were propensity score matched (PSM) with those receiving SMT alone (1:1) for sex, grades of ACLF, CLIF C ACLF scores, and the presence of hepatic encephalopathy. The primary outcomes assessed were mortality at 30 and 90 days. Survival analysis was performed using Kaplan Meier survival curves. A total of 1151 patients (ACLF n=864 [75%], AD [without organ failure] n=287 [25%]) were included. Of the patients with ACLF (n=864), grade 1, 2, and 3 ACLF was present in 167 (19.3%), 325 (37.6%), and 372 (43.0%) patients, respectively. Thirty-nine patients received TPE and SMT, and 1112 patients received only SMT. On PSM analysis, there were 38 patients in each group (SMT plus TPE vs SMT alone). In the matched cohort, the 30-days mortality was lower in the TPE arm compared to SMT (21% vs 50%, P=.008), however, the 90-day mortality was not significantly different between the two groups (36.8% vs 52.6%, P=.166); HR, 0.82 (0.44-1.52), P=.549. TPE improves short-term survival in patients with ACLF, but has no significant impact on long-term outcomes. Randomized control trials are needed to obtain a robust conclusion in this regard.

Five-year all-cause mortality in critically ill liver transplant patients with coronary artery disease: analysis of acute-on chronic liver failure

Patients with acute-on-chronic liver failure (ACLF) are critically ill and have high waiting-list mortality. Although studies demonstrated that appropriately treated coronary artery disease (CAD) should not be regarded as a contraindication to liver transplant (LT), data regarding long-term outcomes in critically ill liver LT recipients are lacking. The aim of this study was to compare the rates of all-cause death at 5 years following LT in patients with ACLF with or without CAD. Between 2010 and 2020, we evaluated 921 consecutive LT patients (MELD score, 32 ± 9) and ACLF classified by CLIF-C ACLF score. Up to 5-year all-cause death according to the CAD status was examined. CAD was defined as a preoperative history of coronary artery bypass graft or a percutaneous intervention and old myocardial infarction. Kaplan-Meier survival analysis was used. Up to 5 years, 212 (23.0%) of all ACLF patients (n = 921) in whom 17 (29.3%) of 58 CAD patients died. In patients with CAD (6.3%, 58/921), the Kaplan-Meier cumulative mortality rate at 5 years was numerically higher but was not statistically significant when compared with those without CAD (32.9% vs. 23.5%, log-rank, P = 0.25). In subgr oup analysis, there were comparable risks of cumulative mortalities at 5 years across the stratification of ACLF grade 1, 2, and 3 (log-rank P = 0.062, P = 0.72, and P = 0.999, respectively). All-cause mortality is high in patients with ACLF after LT but is not related to the presence of revascularized or treated CAD, across the stratification of ACLF grades.

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.

A retrospective study on use of palliative care for patients with alcohol related end stage liver disease in United States.

BACKGROUNDPalliative care (PC) has been shown to be beneficial in end stage liver disease (ESLD), yet the hospitalization data for PC utilization is unknown.AIMTo identify the trend of PC utilization for the special population of alcohol-associated ESLD patients, factors affecting its use and ascertain its impact on healthcare utilization. METHODSWe analyzed around 78 million discharges from the 2007-2014 national inpatient sample and 2010-2014 national readmission database including adult patients admitted for decompensated alcohol-associated cirrhosis. We identified patients with PC consultation as a secondary diagnosis. Odds ratios (OR) and means were adjusted for confounders using multivariate regression analysis models.RESULTSOut of the total 1421849 hospitalizations for decompensated liver cirrhosis, 62782 (4.4%) hospitalizations had a PC consult, which increased from 0.8% (1258) of all alcohol-associated ESLD hospitalizations in 2007 to 6.6% in 2014 (P < 0.01). Patient and hospital characteristics associated with increased odds of PC utilization were advanced age, lower income, Medicaid coverage, teaching institution, urban location, length of stay > 3 d, prolonged ventilation, and administration of total parenteral nutrition (all P < 0.01). Palliative encounters in alcohol-associated ESLD and acute-on-chronic liver failure (ACLF) score were associated with increased odds of discharge to a rehabilitation facility, but significantly lower odds of 30-d readmissions (aOR: 0.35, 95%CI: 0.31-0.41), lower total hospitalization charges and lower mean hospitalization days (all P < 0.01).CONCLUSIONInpatient PC is sparingly used for patients with decompensated alcohol related liver disease, however it has increased over the past decade. PC consultation is associated with lower 30-d readmission rates on multivariate analysis, and lower hospitalization cost and length of stay in patients with ACLF score ≥ 2.

Current pathophysiological concepts of acute decompensation in patients with liver cirrhosis and prognostic scores in different stages of disease

Acute decompensation and acute-on chronic liver failure (ACLF) are associated with a significant reduced prognosis. Previously, the pathophysiological concept of acute decompensation was mainly based on the peripheral vasodilatation hypothesis. However, during the last years, systemic inflammation was recognized as a major driver for decompensation of liver cirrhosis and ACLF. Further, it has been shown that systemic inflammation is associated with the clinical course and the prognosis of the patients. Inflammation also affects the function of extrahepatic organs and therefore leads to the development of an inflammatory cirrhotic multi-organ syndrome. The importance of systemic inflammation in the context of decompensated liver cirrhosis is also transferred to new clinical scores such as the CLIF-C AD and CLIF-C ACLF score. In this article, we provide an overview of the new systemic inflammation hypothesis of decompensated cirrhosis and also discuss current clinical scores for prognostication in different stages of liver cirrhosis.

Influence of Advanced Organ Support (ADVOS) on Cytokine Levels in Patients with Acute-on-Chronic Liver Failure (ACLF).

Background: ADVanced Organ Support (ADVOS) is a novel type of extracorporeal albumin dialysis that supports multiorgan function in patients with acute-on-chronic liver failure (ACLF). No data exist on whether ADVOS affects inflammatory cytokine levels, which play a relevant role in ACLF. Aim: Our aim was to quantify cytokine levels both before and after a single ADVOS treatment in patients with ACLF at a regular dialysis ward. Methods and results: In this prospective study, 15 patients (60% men) with ACLF and an indication for renal replacement therapy were included. Patient liver function was severely compromised, reflected by a median CLIF-consortium ACLF score of 38 (IQR 35; 40). Blood samples were directly taken before and after ADVOS dialysis. The concentration of cytokines for IL-1β, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33 were quantified via a cytometric bead array. We found no significant (p > 0.05) change in cytokine levels, even when patients were stratified for dialysis time (<480 min versus ≥480 min). The relevance of the assessed cytokines in contributing to systemic inflammation in ACLF was demonstrated by Ingenuity pathway analysis®. Conclusion: Concentrations of pathomechanistically relevant cytokines remained unchanged both before and after ADVOS treatment in patients with ACLF.

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.

Impact of acute decompensation on the prognosis of patients with hepatocellular carcinoma.

Organ failure in patients with acute decompensation (AD) is a defining characteristic of acute-on-chronic liver failure (ACLF). However, the clinical features of AD during the long-term clinical course of hepatocellular carcinoma (HCC) are still poorly understood. This study aimed to clarify features and impact of AD/ACLF on the prognosis of patients after treatment for HCC. This retrospective study enrolled 556 consecutive patients who were initially diagnosed with HCC, and analyses were conducted taking into account HCC treatment type, HCC stage, and presence or absence of cirrhosis. During follow-up, 299 patients with AD were hospitalized. AD occurrence is closely related to prognosis, regardless of the presence or absence of cirrhosis and HCC stage, and early-onset AD (within 90 days after HCC treatment) has negative impact on prognosis. In the intermediate-advanced-stage group, surgical resection had a positive impact on AD incidence post-treatment. After systemic therapy for HCC, renal impairment was the predictive factors for AD development. The 28/90-day mortality rate was higher among 41 cases (13.7%) with AD who exhibited ACLF as compared with cases without ACLF. AD without cirrhosis had similar ACLF incidence and short-term mortality, compared to AD with cirrhosis. The prognostic model using a decision-tree-based approach, which includes ACLF, bilirubin level, HCC progression, and MELD score is useful for predicting 90- or 28-day mortality after AD diagnosis. Careful management of patients with HCC who are hospitalized with AD is necessary, considering ACLF, HCC progression, and liver function.

A neutrophil-to-lymphocyte ratio-based prognostic model to predict mortality in patients with HBV-related acute-on-chronic liver failure

BackgroundAlthough the Asian Pacific Association for the Study of the Liver acute-on-chronic liver failure (ACLF) research consortium (AARC) ACLF score is easy to use in patients with hepatitis b virus-related ACLF (HBV-ACLF), serum lactate is not routinely tested in primary hospitals, and its value may be affected by some interference factors. Neutrophil-to-lymphocyte ratio (NLR) is used to assess the status of bacterial infection (BI) or outcomes in patients with various diseases. We developed an NLR-based AARC ACLF score and compared it with the existing model.MethodsA total of 494 HBV-ACLF patients, enrolled in four tertiary academic hospitals in China with 90-day follow-up, were analysed. Prognostic performance of baseline NLR and lactate were compared between cirrhotic and non-cirrhotic subgroups via the receiver operating curve and Kaplan–Meier analyses. A modified AARC ACLF (mAARC ACLF) score using NLR as a replacement for lactate was developed (n = 290) and validated (n = 204).ResultsThere were significantly higher baseline values of NLR in non-survivors, patients with admission BI, and those with higher grades of ACLF compared with the control groups. Compared with lactate, NLR better reflected BI status in the cirrhotic subgroup, and was more significantly correlated with CTP, MELD, MELD-Na, and the AARC score. NLR was an independent predictor of 90-day mortality, and was categorized into three risk grades (< 3.10, 3.10–4.78, and > 4.78) with 90-day cumulative mortalities of 8%, 21.2%, and 77.5% in the derivation cohort, respectively. The mAARC ACLF score, using the three grades of NLR instead of corresponding levels of lactate, was superior to the other four scores in predicting 90-day mortality in the derivation (AUROC 0.906, 95% CI 0.872–0.940, average P < 0.001) and validation cohorts (AUROC 0.913, 95% CI 0.876–0.950, average P < 0.01), with a considerable performance in predicting 28-day mortality in the two cohorts.ConclusionsThe prognostic value of NLR is superior to that of lactate in predicting short-term mortality risk in cirrhotic and non-cirrhotic patients with HBV-ACLF. NLR can be incorporated into the AARC ACLF scoring system for improving its prognostic accuracy and facilitating the management guidance in patients with HBV-ACLF in primary hospitals.

From the Editor’s desk…

From the Editor’s desk…

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.

ACUTE-ON-CHRONIC LIVER FAILURE IS INDEPENDENTLY ASSOCIATED WITH LOWER SURVIVAL IN PATIENTS WITH SPONTANEOUS BACTERIAL PERITONITIS.

Spontaneous bacterial peritonitis (SBP) is a decompensation of cirrhosis with an in-hospital mortality ranging from 20% to 40%. The purpose of this study is to analyze if EASL-CLIF definition of acute-on-chronic liver failure (ACLF) is able to predict mortality in cirrhotic patients with SBP. Historical cohort study conducted in a public tertiary care teaching hospital. Data from medical records from January 2009 to July 2016 were obtained by searching the hospital electronic database for samples of ascites collected in the period. Electronic and physical medical records were analyzed and patients were included if they were over 18-years old, with cirrhosis and an ascites fluid compatible with SBP: 69 patients were included. Liver-specific scores were calculated and Kaplan-Meier survival analysis was used for univariate analysis and a stepwise approach to the Cox regression for multivariate analysis. All cause mortality was 44%, 56.5% and 74% for 28-, 90- and 365-day, respectively. The prevalence of ACLF was 58%. Of these, 65% grade 1, 17.5% grade 2 and 17.5% grade 3. In multivariate analysis, the use of proton-pump inhi-bitors, alanine transaminase lower than 40 U/L, hemoglobin higher than 9 g/dL, absence of ACLF and lower CLIF-SOFA and MELD scores were independently associated with higher survival for both 28- and 90-day interval. The presence of ACLF and higher CLIF-SOFA scores were independently associated with higher 28- and 90-day mortality in cirrhotic patients admitted due to SBP.

Prognostic Factors Related to the Mortality Rate of Acute-on-Chronic Liver Failure Patients.

BackgroundCritical illness-related corticosteroid insufficiency (CIRCI) is known to be a common complication in patients with acute-on-chronic liver failure (ACLF). However, factors that predict the survival rate of ACLF patients remain unclear. The present study aims to determine the prognostic factors that impinge on the survival rate of ACLF patients.MethodsA total of 90 patients with ACLF at different stages, with or without CIRCI, were prospectively evaluated.ResultsVarious clinical factors were found to be significantly different among patients at early, mid and late stages of ACLF, as well as between the same population of patients with and without CIRCI. Specifically, patients at later stages of ACLF and patients with CIRCI had significantly higher Child–Turcotte–Pugh (CTP), Model for End-Stage Liver Disease (MELD) and ACLF Research Consortium (AARC)-ACLF scores. CIRCI was observed in 20% of the enrolled patients (18 out of 90). In addition, the 90-day mortality rate was higher in mid- and late-stage ACLF patients, as well as patients with CIRCI.ConclusionACLF stage and CIRCI predict early mortality in patients with ACLF and could be actively monitored in these patients for prioritized liver transplantation.

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.

A Methodology to Generate Longitudinally Updated Acute-On-Chronic Liver Failure Prognostication Scores From Electronic Health Record Data.

Queries of electronic health record (EHR) data repositories allow for automated data collection. These techniques have not been used in hepatology due to the inability to capture hepatic encephalopathy (HE) grades, which are inputs for acute‐on‐chronic liver failure (ACLF) models. Here, we describe a methodology to use EHR data to calculate rolling ACLF scores. We examined 239 patient admissions with end‐stage liver disease from July 2014 to June 2019. We mapped EHR flowsheet data to determine HE grades and calculated two longitudinally updated ACLF scores. We validated HE grades and ACLF diagnoses by chart review and calculated sensitivity, specificity, and Cohen’s kappa. Of 239 patient admissions analyzed, 37% were women, 46% were non‐Hispanic white, median age was 60 years, and the median Model for End‐Stage Liver Disease–Na score at admission was 25. Of the 239, 7% were diagnosed with ACLF as defined by the North American Consortium for the Study of End‐Stage Liver Disease (NACSELD) diagnostic criteria at admission, 27% during the hospitalization, and 9% at discharge. Forty percent were diagnosed with ACLF by the European Association for the Study of the Liver– Chronic Liver Failure Consortium (CLIF‐C) diagnostic criteria at admission, 51% during the hospitalization, and 34% at discharge. From the chart review of 51 admissions, we found sensitivities and specificities for any HE (grades 1‐4) were 92%‐97% and 76%‐95%, respectively; for severe HE (grades 3‐4), sensitivities and specificities were 100% and 78%‐98%, respectively. Cohen’s kappa between flowsheet and chart review of HE grades ranged from 0.55 to 0.72. Sensitivities and specificities for NACSELD‐ACLF diagnoses were 75%‐100% and 96%‐100%, respectively; for CLIF‐C‐ACLF diagnoses, these were 91%‐100% and 96‐100%, respectively. We generated approximately 28 unique ACLF scores per patient per admission day. Conclusion: We developed an informatics‐based methodology to calculate longitudinally updated ACLF scores. This opens new analytic potentials, such as big data methods, to develop electronic phenotypes for patients with ACLF.

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.

Validating a novel score based on interaction between ACLF grade and MELD score to predict waitlist mortality

Among candidates listed for liver transplant (LT), the model for end-stage liver disease (MELD) score may not capture acute-on-chronic liver failure (ACLF) severity. Data on the interaction between ACLF and MELD score in predicting waitlist mortality are scarce. We analyzed the UNOS database (01/2002 to 06/2018) for LT listings in adults with cirrhosis and ACLF (without hepatocellular carcinoma). ACLF grades 1, 2, 3a, and 3b- were defined using the modified EASL-CLIF criteria. Of 18,416 candidates with ACLF at listing (mean age 54 years, 69% males, 63% Caucasians), 90-day waitlist mortality (patient death or being too sick for LT) was 21.6% (18%, 20%, 25%, and 39% for ACLF grades 1, 2, 3a, and 3b, respectively). Using a Fine and Gray regression model, we identified an interaction between MELD and ACLF grade, with ACLF having a higher impact at lower MELD scores. Other variables included candidate's age, sex, liver disease etiology, listing MELD, ACLF grade, obesity, and performance status. A score developed using parameter estimates from the interaction model on the derivation cohort (n = 9,181) stratified the validation cohort (n= 9,235) into quartiles: Q1 (score <10.42), Q2 (10.42-12.81), Q3 (12.82-15.50), and Q4 (>15.50). Waitlist mortality increased with each quartile from 13%, 18%, 23%, and 36%, respectively. Observed vs. expected waitlist mortality deciles in the validation cohort showed good calibration (goodness of fit p= 0.98) and correlation (R= 0.99). Among selected candidates who have ACLF at listing, MELD score and ACLF interact in predicting cumulative risk of 90-day waitlist mortality, with higher impact of ACLF grade at lower listing MELD score. Validating these findings in large prospective studies will support consideration of both MELD and ACLF when prioritizing transplant candidates and allocating liver grafts. In patients with cirrhosis listed for liver transplantation, the presence of multiorgan failure, a condition referred to as acute-on-chronic liver failure, is associated with high waiting list mortality rates. Current organ allocation policy disadvantages patients with this condition. This study describes and validates a new scoring method that performs better than the currently available scoring systems. Further validation of this approach may reduce the deaths of patients with cirrhosis and acute-on-chronic liver failure on the transplant waiting list.

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.