Chronic Liver Failure-sequential Organ Failure Research Articles

Weighted thyroid-stimulating hormone disturbance in prognosis of hepatitis B virus-related acute-on-chronic liver failure.

To weight the prognostic value of thyroid hormones in catastrophic acute-on-chronic liver failure (ACLF). A retrospective cohort (n=635) and two prospective cohorts (n=353, and 198) were enrolled in this study. The performance of a novel developed prognostic score was assessed from aspects of reliability, discrimination, and clinical net benefit. Thyroid-stimulating hormone (TSH) was identified to have the most potential as a prognostic predictor for hepatitis B virus-related ACLF among thyroid hormones. The novel score (modified chronic liver failure-organ failure score [mCLIF-OFs]) was developed with weighted TSH and other scored organs in the CLIF-OFs using the retrospective cohort (n=635). The predicted risk and observed probabilities of death were comparable across the deciles of mCLIF-OFs (Hosmer-Lemeshow χ2 =4.28, p=0.83; Brier scaled=11.9). The C-index of mCLIF-OFs (0.885 [0.883-0.887]) for 30-day mortality was significantly higher than that of the CLIF-OFs, chronic liver failure-sequential organ failure assessment score (CLIF-SOFAs), CLIF-C ACLFs, Model of End-stage Liver Disease (MELD), and Child-Pugh (all p<0.001). The absolute improvements of prediction error rates of the mCLIF-OFs compared to the above five scores were from 19.0% to 61.1%. After the analysis of probability density function, the mCLIF-OFs showed the least overlapping coefficients (27.9%) among the above prognostic scores. Additionally, the mCLIF-OFs showed greater net benefit than the above five prognostic scores over a wide range of risk threshold of death. Similar results were validated in two prospective ACLF cohorts with HBV and non-HBV etiologies. Weighted TSH portended the outcome of ACLF patients, which could be treated as a "damaged organ" of the hypothalamic-pituitary-thyroid axis. The novel mCLIF-OFs is a reliable prognostic score with better discrimination power and clinical net benefit than CLIF-OFs, CLIF-SOFAs, CLIF-C ACLFs, MELD, and Child-Pugh.

Plasma human neutrophil peptides as biomarkers of disease severity and mortality in patients with decompensated cirrhosis.

Human neutrophil peptides (HNP)-1, -2 and -3 are the most abundant proteins in neutrophil azurophilic granules and are rapidly released via neutrophil degranulation upon activation. The aims of our study were to assess the role of HNP1-3 as biomarkers of disease severity in patients with decompensated cirrhosis and their value in predicting short-term mortality. In this study, 451 patients with acutely decompensated cirrhosis (AD) were enrolled at the two medical centres. Overall, 281 patients were enrolled as the training cohort from October 2015 to April 2019, and 170 patients were enrolled as the validation cohort from June 2020 to February 2021. Plasma HNP1-3 levels were measured using enzyme-linked immunosorbent assay (ELISA). Plasma HNP1-3 increased stepwise with disease severity (compensated cirrhosis: 0.3 (0.2-0.4); AD without acute-on-chronic liver failure (ACLF): 1.9 (1.3-4.8); ACLF-1: 2.3 (1.8-6.1); ACLF-2: 5.6 (2.9-12.3); ACLF-3: 10.3 (5.7-17.2)ng/ml). From the multivariate Cox regression analysis, HNP1-3 emerged as independent predictors of mortality at 30 and 90 days. Similar results were observed in the subgroup analysis. On ROC analysis, plasma HNP1-3 showed better predictive accuracy for 30- and 90-day mortality (area under the receiver operating characteristic (AUROC) of 0.850 and 0.885, respectively) than the neutrophil-to-lymphocyte ratio (NLR) and similar accuracy as end-stage liver disease (MELD: 0.881 and 0.874) and chronic liver failure-sequential organ failure (CLIF-SOFA: 0.887 and 0.878). Plasma HNP1-3 levels were closely associated with disease severity and might be used to identify patients with AD at high risk of short-term mortality.

Acute Liver Failure Prognostic Criteria: It's Time to Revisit.

Acute liver failure (ALF) is a devastating disease, and patients are at a higher risk of death without liver transplantation. Indicators are needed to identify the risk of death in ALF, which will help in the timely referral of patients to specialized centers. Clichy criteriaand King's College Hospital (KCH) criteria are the most widely used prognostic criteria. Real-life application of Clichy criteria is limited due to the non-availability of factor V level measurement. KCH criteria have good specificity but low sensitivity to predict outcomes. Therefore, we attempted to use the model for end-stage liver disease (MELD) score and chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score in ALF patients as prognostic indicators and need for liver transplantation. Forty-one patients with ALF were enrolled in the study. On the day of admission, MELD and CLIF-SOFA scores were calculated for each patient. Area under receiver operating characteristics (AUROC) curve, sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and diagnostic accuracy (DA) of MELD and CLIF-SOFA score were calculated to predict the outcome of the patients. Out of 41 patients, nine patients left against medical advice. The sensitivity, specificity, PPV, NPV, and DA for the MELD score of enrolled patients in the study were 81.5%, 62.5%, 59.5%, 83.3%, 70.1%, and for the CLIF-SOFA score of enrolled patients in the study were 88.9%, 90.0%, 85.7%, 92.3%, 89.6% respectively. Patients who did not survive had higher INR, MELD, CLIF-SOFA scores, and hepatic encephalopathy (HE) grades. Five patients who had a combination of MELD ≥30 and CLIF-SOFA ≥10, expired. In our study, we used MELD score and CLIF-SOFA as prognostic markers, and we concluded that CLIF-SOFA is a better predictor of mortality than MELD score in terms of sensitivity, specificity, NPV, PPV, and diagnostic accuracy. AUROC for CLIF-SOFA score is higher when compared to the MELD score.

New Algorithm Rules Out Acute-on-chronic Liver Failure Development within 28 Days from Acute Decompensation of Cirrhosis.

Approximately 10% of patients with acute decompensated (AD) cirrhosis develop acute-on-chronic liver failure (ACLF) within 28 days. Such cases have high mortality and are difficult to predict. Therefore, we aimed to establish and validate an algorithm to identify these patients on hospitalization. Hospitalized patients with AD who developed ACLF within 28 days were considered pre-ACLF. Organ dysfunction was defined according to the chronic liver failure-sequential organ failure assessment (CLIF-SOFA) criteria, and proven bacterial infection was taken to indicate immune system dysfunction. A retrospective multicenter cohort and prospective one were used to derive and to validate the potential algorithm, respectively. A miss rate of <5% was acceptable for the calculating algorithm to rule out pre-ACLF. In the derivation cohort (n=673), 46 patients developed ACLF within 28 days. Serum total bilirubin, creatinine, international normalized ratio, and present proven bacterial infection at admission were associated with the development of ACLF. AD patients with ≥2 organ dysfunctions had a higher risk for pre-ACLF patients [odds ratio=16.581 95% confidence interval: (4.271-64.363), p<0.001]. In the derivation cohort, 67.5% of patients (454/673) had ≤1 organ dysfunction and two patients (0.4%) were pre-ACLF, with a miss rate of 4.3% (missed/total, 2/46). In the validation cohort, 65.9% of patients (914/1388) had ≤1 organ dysfunction, and four (0.3%) of them were pre-ACLF, with a miss rate of 3.4% (missed/total, 4/117). AD patients with ≤1 organ dysfunction had a significantly lower risk of developing ACLF within 28 days of admission and could be safely ruled out with a pre-ACLF miss rate of <5%.

Establishment of MELD-lactate clearance scoring system in predicting death risk of critically ill cirrhotic patients

BackgroundTo develop a scoring system related to the lactate clearance (ΔLA) to predict the mortality risk (MELD-ΔLA) for critically ill cirrhotic patients.MethodsIn this retrospective cohort study, 881 critically ill cirrhotic patients from the Medical Information Mart for Intensive Care (MIMIC-III) database were included eventually. The outcomes of our study were defined as ICU death, 28-day, 90-day and 1-year mortality. Predictors were identified by multivariate Cox analysis to develop the predictive scoring system. The C-index and area under the curve (AUC) of receiver operator characteristic curve (ROC) were used to identify the predicting performance of the MELD-ΔLA, sequential organ failure assessment (SOFA), chronic liver failure-sequential organ failure assessment (CLIF-SOFA), the model for end-stage liver disease (MELD), Child–Pugh, chronic liver failure consortium acute-on-chronic liver failure (CLIF-C ACLF), chronic liver failure consortium-acute decompensation (CLIF-C AD) and MELD-Na scoring systems. Additionally, subgroup analysis was also performed based on whether critically ill cirrhotic patients underwent liver transplantation.ResultsCreatinine, bilirubin, international normalized ratio (INR), lactate first, ΔLA and vasopressors were closely associated with ICU death of liver critically ill cirrhotic patients. The C-index of the MELD-ΔLA in ICU death was 0.768 (95% CI 0.736–0.799) and the AUC for the MELD-ΔLA scoring system in predicting 28-day, 90-day, and 1-year mortality were 0.774 (95% CI 0.743–0.804), 0.765 (95% CI 0.735–0.796), and 0.757 (95% CI 0.726–0.788), suggested that MELD-ΔLA scoring system has a good predictive value than SOFA, CLIF-SOFA, MELD, Child–Pugh, CLIF-C ACLF, CLIF-C AD) and MELD-Na scoring systems. Additionally, the study also confirmed the good predictive value of MELD-ΔLA scoring system for critically ill cirrhotic patients regardless of undergoing liver transplantation.ConclusionThe developed MELD-ΔLA score is a simple scoring system in predicting the risk of ICU death, 28-day, 90-day and 1-year mortality for critically ill cirrhotic patients, which may have a good predictive performance.

Comparison of Scoring Systems for Prognosis in Cirrhotic Patients Admitted with Hepatic Encephalopathy

Objective: To compare various scoring systems to predict the prognosis in patients of cirrhosis presenting with hepatic encephalopathy at Pak Emirates Military Hospital Rawalpindi.&#x0D; Study Design: Cross-sectional study.&#x0D; Place and Duration: Gastroenterology Department, Pak Emirates Military Hospital Rawalpindi, from Sep 2018 to Feb 2019.&#x0D; Methodology: This study was conducted on 55 patients suffering from liver cirrhosis and presetting with hepatic encephalopathy at our hospital. Diagnosis of liver cirrhosis and hepatic encephalopathy was made by a consultant gastroenterologist based on clinical findings and relevant investigations. Chronic liver failure-sequential organ failure assessment (CLIF-SOFA), Model for end stage liver disease (MELD), and Child-Turcotte-Pugh (CTP) scores were calculated for all patients within the first 24 hours of presentation. Outcome in the study was patient either discharged or deceased at the end of study. Comparison was made between the three scores that which is a better predictor for prognosis of these patients.&#x0D; Results: Out of 55 patients included in the final analysis 35 were male and 20 were female. Commonest etiology of hepatic encephalopathy was Infection followed by Constipation.10 patients had grade 1 encephalopathy, 15 had grade 2, 20 had grade 3 while 10 had grade 4 encephalopathy. CLIF-SOFA emerged as better predictor for prognosis followed by MELD and CTP.&#x0D; Conclusion: CLIF-SOFA was the best of all scores in predicting the prognosis of patients suffering from liver cirrhosis presenting with hepatic encephalopathy. MELD and CTP were also significant in this regard but less as compared to CLIFSOFA.

Predicting in-hospital mortality of cirrhotic patients hospitalized with hepatic encephalopathy

BackgroundHepatic encephalopathy (HE) is a serious condition associated with high rates of mortality. Many scoring systems are used to predict the outcome of HE in patients admitted to the intensive care unit (ICU). The most used scores are Child-Turcotte-Pugh (CTP), Model for End-stage Liver Disease (MELD), Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II). These scores were thoroughly investigated in HE associated with acute liver failure (type A). In the present study, we aimed to evaluate the prognostic value of these scores in patients with HE on a background of liver cirrhosis (type C). Two hundred cirrhotic patients hospitalized with HE were included in the study. Diagnosis and classification of HE were based on the West Haven criteria. APACHE II, CLIF-SOFA, MELD, MELD-Na, and CTP scores were calculated for all patients within the first 24 h after admission. According to survival outcomes, patients were categorized into either improved or deceased. Demographic, clinical, and laboratory data as well as prognostic scores were compared in both deceased and improved groups. The receiver operating characteristic (ROC) curve was plotted, and the area under the ROC curve (AUROC) was calculated for each score. Backward logistic regression analysis was used to identify the predictors of mortality.Results60.5% of patients were males. The mean age was 61.09 ± 8.94 years. The main precipitating factors of HE was infections predominantly spontaneous bacterial peritonitis (n = 108, 54.0%) followed by variceal bleeding (n = 39, 19.5%). All scores were significantly higher in the deceased patients. AUROC were 0.734 (CI95% 0.666–0.803), 0.717 (CI95% 0.647–0.787), 0.663 (CI95% 0.589–0.738), 0.626 (CI95% 0.549–0.704), and 0.609 (CI95% 0.531–0.686) for CLIF-SOFA, MELD-Na, MELD, APACHE II, and CTP scores, respectively. MELD, MELD-Na, and CLIF-SOFA scores were the independent predictors of mortality. Among these scores, CLIF-SOFA was the strongest independent predictor of mortality (OR = 1.142, CI95% = 0.888–1.467, p = 0.001).ConclusionsCLIF-SOFA score was superior to other prognostic scores in predicting mortality in hospitalized patients with HE type C.

The Significant Morbidity and Mortality Indicators in Patients of Cirrhosis

Background: Cirrhosis progression varies greatly from patient to patient due to a variety of factors, including hepatic reserve, cirrhosis etiology, and the presence of hepatocellular cancer. As a result, determining a prognosis in a patient with cirrhosis remains a difficult task. For nearly three decades, the Child-Pugh score (CPS) has been the gold standard for determining the prognosis of cirrhosis. In the last two decades, many prognostic models and scores like a model for end-stage liver disease (MELD), chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score, peripheral blood lymphocyte to monocyte ratio (LMR) have been presented to predict prognosis in patients with cirrhosis and to choose the best therapy option. The aim of our study is to determine which score is more effective in predicting three-month mortality and whether these scores are equally effective in predicting short-term outcomes.Materials & methods: In this hospital-based longitudinal study, we analyzed 140 patients with cirrhosis of liver visiting All India Institute of Medical Sciences Bhopal between July 2019 and July 2020. All the 140 patients were followed up for three months to establish short-term outcomes. The blood investigations were done at the time of presentation from all the patients and after three months in the survivors. Various scores were calculated.Results: The majority of patients (47%) were in Child-Pugh class C. Mean MELD score was 13.54, LMR score was 1.96 and CLIF-SOFA score was 5. The total bilirubin, serum creatinine, international normalized ratio (INR), total leukocyte count, absolute monocyte count, CPS, MELD, CLIF-SOFA were significantly higher in a non-surviving group as compared to the surviving group, whereas the albumin and LMR significantly decreased in the non-surviving group. On performing multivariate regression, LMR and CLIF-SOFA were significant independent risk factors of mortality after adjusting for confounding factors. All the parameters had significant discriminatory power to predict mortality. Discriminatory power of CLIF-SOFA (AUC 0.808; 95% CI: 0.733 to 0.870) was excellent and discriminatory power of CPS (AUC 0.792; 95% CI: 0.716 to 0.856), MELD score (AUC 0.765; 95% CI: 0.685 to 0.832) and LMR (AUC 0.75; 95% CI: 0.669 to 0.819) was acceptable. Among all the parameters, CLIF-SOFA was the best predictor of mortality at a cut-off point of >5 with 80.80% chances of correctly predicting mortality.Conclusion: The significant morbidity and mortality indicators are high total bilirubin, high creatinine, high INR, high TLC, low platelet count, and low albumin. Among the various scores, CLIF-SOFA is a better predictor of mortality and morbidity. Low LMR and high CLIF-SOFA are significant independent risk factors of mortality at three months.

The Relationship between FT3 Level and Severity of HBV-ACLF.

We aimed to explore the relationship between free triiodothyronine (FT3) level and severity of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). A total of 122 patients with HBV-ACLF who were hospitalized in Beijing You'an Hospital Affiliated to Capital Medical University from September 2018 to February 2020 were included in this study. The FT3 level and the number of organs involved in patients with different stages of liver failure were analyzed. The patients were divided into four groups, Q1, Q2, Q3, and Q4, according to FT3 level. Correlation analysis was used to compare the correlation between FT3 level and Model for End-Stage Liver Disease (MELD) score, chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score, CLIF-consortium organ failure (CLIF-COF) score, and Asian Pacific Association for the Study of the Liver (APASL) acute-on-chronic liver failure (ACLF) Research Consortium (AARC) score. Multiple linear regression, logistic regression and receiver operating characteristic (ROC) curve were used to analyze the effect of FT3 on MELD score. The FT3 level was the lowest in patients with advanced HBV-ACLF, but the highest in patients with early-stage HBV-ACLF (P < 0.01). The more organs involved, the lower the level of FT3 (P < 0.01). The MELD score of Q4 group was the lowest, whereas that of Q1 group was the highest (P < 0.01). Pearson correlation coefficients of FT3 with MELD score, CLIF-SOFA score, CLIF-COF score and AARC score were -0.477, -0.359, -0.347, and -0.391, respectively (P < 0.001). Multiple linear regression analysis showed that the partial regression coefficients of FT3, natural log total bilirubin in milligrams per decaliter {ln[TBIL (mg/dL)]}, natural log creatinine in milligrams per decaliter {ln[CR (mg/dL)]}, and natural log international normalized ratio {ln[INR]} were -0.215, 0.346, 0.231, and 0.667, respectively (P < 0.001). The odds ratio (OR) values of FT3, ln[TBIL (mg/dL)], ln[CR (mg/dL)], and ln[INR] were 0.141 (0.082-0.244), 5.426 (2.697-9.059), 4.535 (2.432-8.455), and 8.642 (6.679-10.267) in the MELD ≥ 30 group compared with MELD < 30 group (P < 0.001). Furthermore, their area under the ROC curve (AUROC) values were 0.739 (0.686-0.792), 0.748 (0.696-0.800), 0.632 (0.562-0.702), and 0.933 (0.903-0.963), respectively (P < 0.001). FT3 level is correlated with the severity of HBV-ACLF, which may be one of the factors to judge the severity of this disease.

Proton Pump Inhibitor Therapy Does Not Affect Prognosis of Cirrhosis Patients With Acute Decompensation and Acute-on-Chronic Liver Failure: A Single-Center Prospective Study.

Background: The aim of this study was to investigate the impact of proton pump inhibitor (PPI) therapy on complications and prognosis in cirrhosis patients with and without acute-on-chronic liver failure (ACLF).Materials and Methods: Cirrhosis patients with acute decompensation (AD) (n = 489) admitted in our center were enrolled in this prospective observational cohort study. According to treatment received, patients were identified as users or nonusers of PPI. Clinical and laboratory data, complications during hospitalization, and overall survival were recorded in all the patients.Results: Of the 489 patients, 299 (61.1%) patients received PPI therapy. The logistic regression analysis showed that age, albumin, history of previous hepatic encephalopathy (HE), and the chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score were independent risk factors for HE in patients with decompensated cirrhosis [odds ratio (OR) = 1.07, 95% CI: 1.03–1.12, p = 0.001; OR = 1.13, 95% CI: 1.04–1.24, p = 0.006; OR = 242.52, 95% CI: 40.17–1464.11, p < 0.001; and OR = 2.89, 95% CI: 2.11–3.96, p < 0.001, respectively]. Previous severe liver injury and previous bacterial infections were independent risk factors for spontaneous bacterial peritonitis (SBP) in patients with decompensated cirrhosis (OR = 3.43, 95% CI: 1.16–10.17, p = 0.026 and OR = 6.47, 95% CI: 2.29–18.29, p < 0.001, respectively). The multivariate Cox proportional hazards regression model showed that the type and dose of the PPI used were not related to 28-day and 90-day mortality in cirrhosis patients with AD or ACLF.Conclusion: PPI use does not appear to increase mortality or the risk of HE and SBP in the hospitalized cirrhosis patients with and without ACLF.

Acute-on-chronic liver failure in children.

Although various complex definitions of acute-on-chronic liver failure (ACLF) have been suggested in relation to adult patients, there is currently no universal definition of the syndrome in pediatric patients. In simplified terms, ACLF is characterized by the acute deterioration of the liver functions due to the effects of a precipitating factor on the basis of a chronic liver disease. Acute events and underlying liver diseases are very different in children from those seen in adults. Moreover, acute events and underlying chronic liver diseases vary among geographical regions, although it seems that the most common such diseases and acute events are autoimmune hepatitis, Wilson’s disease, and their flares. ACLF is associated with a poor prognosis. While no scoring systems have been developed to predict the prognosis for children with ACLF, modified versions of the Asian Pacific Association for the Study of the liver’s acute-on-chronic liver failure scoring system and the Chronic Liver Failure-Sequential Organ Failure Assessment criteria can be used in children until specific and validated scoring systems are available. Aside from liver transplantation, there is no proven treatment for ACLF. Thus, the early recognition of ACLF prior to the development of extrahepatic organ failure is important.

Dysregulation of the Lysophosphatidylcholine/Autotaxin/Lysophosphatidic Acid Axis in Acute-on-Chronic Liver Failure Is Associated With Mortality and Systemic Inflammation by Lysophosphatidic Acid-Dependent Monocyte Activation.

Acute-on-chronic liver failure (ACLF) is characterized by systemic inflammation, monocyte dysfunction, and susceptibility to infection. Lysophosphatidylcholines (LPCs) are immune-active lipids whose metabolic regulation and effect on monocyte function in ACLF is open for study. Three hundred forty-two subjects were recruited and characterized for blood lipid, cytokines, phospholipase (PLA), and autotaxin (ATX) concentration. Peripheral blood mononuclear cells and CD14+ monocytes were cultured with LPC, or its autotaxin (ATX)-derived product, lysophosphatidic acid (LPA), with or without lipopolysaccharide stimulation and assessed for surface marker phenotype, cytokines production, ATX and LPA-receptor expression, and phagocytosis. Hepatic ATX expression was determined by immunohistochemistry. Healthy volunteers and patients with sepsis or acute liver failure served as controls. ACLF serum was depleted in LPCs with up-regulated LPA levels. Patients who died had lower LPC levels than survivors (area under the receiver operating characteristic curve, 0.94; P<0.001). Patients with high-grade ACLF had the lowest LPC concentrations and these rose over the first 3days of admission. ATX concentrations were higher in patients with AD and ACLF and correlated with Model for End-Stage Liver Disease, Consortium on Chronic Liver Failure-Sequential Organ Failure Assessment, and LPC/LPA concentrations. Reduction in LPC correlated with higher monocyte Mer-tyrosine-kinase (MerTK) and CD163 expression. Plasma ATX concentrations rose dynamically during ACLF evolution, correlating with IL-6 and TNF-α, and were associated with increased hepatocyte ATX expression. ACLF patients had lower human leukocyte antigen-DR isotype and higher CD163/MerTK monocyte expression than controls; both CD163/MerTK expression levels were reduced in ACLF ex vivo following LPA, but not LPC, treatment. LPA induced up-regulation of proinflammatory cytokines by CD14+ cells without increasing phagocytic capacity. ATX up-regulation in ACLF promotes LPA production from LPC. LPA suppresses MerTK/CD163 expression and increases monocyte proinflammatory cytokine production. This metabolic pathway could be investigated to therapeutically reprogram monocytes in ACLF.

Effectiveness of sepsis bundle application and outcomes predictors to cirrhotic patients with septic shock

IntroductionCirrhotic patients with septic shock have a poorer prognosis compared with the general population. Our study aimed to investigate the survival benefit of the implementation of hour-1 bundle proposed by Surviving Sepsis Campaign, and to analyze the predictors associated with short-term mortality of these patients.MethodsA single-center, retrospective case-control study was conducted among adult patients who visited the emergency department between January 1, 2018 and December 31, 2019. All patients with a diagnosis of liver cirrhosis and septic shock were enrolled. Their baseline characteristics, laboratory results, source of sepsis, and sepsis bundle management were recorded. We further divided the patients into survivor and non-survivor groups to identify independent prognostic factors.ResultsA total of 88 patients were eligible for this study. The overall 30-day mortality rate was 53.4% (47/88). The proportion of hour-1 bundle achievement was 30.7% (27/88). There were no significant mortality differences between the hour-1 bundle achievement and non-achievement groups (44.4% vs. 57.4%, p = 0.35). Compared with the patients in the survivor group, patients in the non-survivor group had significantly more advanced stage of cirrhosis and a lower proportion of receiving source control (4.3% vs. 22.0%, p = 0.02). The chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score (adjusted hazard ratio [AHR] =1.52, p < 0.01), serum lactate (AHR =1.03, p < 0.01), and source control (AHR =0.54, p = 0.02) were identified as independent prognostic factors in the multivariate regression model. Furthermore, the CLIF-SOFA score (area under curve [AUC]: 0.81) and lactate levels (AUC: 0.77) revealed good mortality discrimination ability in cirrhotic patients with septic shock.ConclusionsThe application of the hour-1 bundle did not reveal a significant survival benefit to cirrhotic patients with septic shock. Clinicians could utilize CLIF-SOFA scores and lactate levels for mortality risk stratification and put more emphasis on the feasibility of source control to improve their prognosis.

Predictors and outcome of emergent Liver transplantation for patients with acute-on-chronic liver failure

Background and aimsControversy exists over whether emergent liver transplantation (LT) should be performed for patients with acute-on-chronic liver failure (ACLF), especially for patients with multiple organ failure. MethodsA total of 110 ACLF patients, defined by the European Association for the Study of the Liver (EASL) Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) criteria were analyzed. The primary outcome was overall survival after ACLF diagnosis. ResultsDuring follow-up, 76 patients received LT (59 received deceased-donor LT and 17 patients received living-donor LT). The overall survival was better for patients who received LT than patients who did not (82.9% vs. 17.6%, P < 0.001). Among the 76 patients who received LT, the overall survival was not different according to ACLF grade at diagnosis (70.0%, 85.3%, and 84.4% at one-year for ACLF grades 1, 2, and 3, respectively, P = 0.45). The baseline model for end-stage liver disease (MELD) score and progression of the ACLF grade during the pre-transplant period were independent factors for survival after LT. The one-year survival rate was 92.3% for patients with baseline MELD scores of ≤ 32 without ACLF grade progression, whereas it was 33.3% for those with baseline MELD scores of > 32 and ACLF grade progression. ConclusionsEmergent LT provided a significant survival benefit to ACLF patients, regardless of the baseline ACLF grade. Post-LT outcomes were associated with baseline MELD scores and ACLF progression during the pre-transplant period, which might be used in the emergent LT plan for patients presenting with ACLF.

Acute-on-Chronic Liver Failure in Children: A Single-Center Experience.

Acute-on-chronic liver failure and its outcomes have not yet been evaluated in detail in children. We aimed to evaluate the etiology, acute events, and prognostic factors of acute-on-chronic liver failure in children. Pediatric patients (age 2-18 years) diagnosed with acute-on-chronic liver failure between April 2014 and April 2020 were evaluated retrospectively. Acute-on-chronic liver failure was defined as the presence of acute hepatic insult in previously diagnosed or undiagnosed chronic liver disease causing jaundice (total serum bilirubin ≥5 mg/dL) and coagulopathy (international normalized ratio of ≥2.0) and clinical and/or radiological ascites and/or hepatic encephalopathy within 4 weeks. Acute-on-Chronic Liver Failure Research Consortium and Chronic Liver Failure-Sequential Organ Failure Assessment scores were calculated for patients at first admission and at end of day 5 or before liver transplant. Our study included 29 patients. Underlying chronic liver diseases were mostly autoimmune hepatitis (51.72%) and Wilson disease (27.58%), with flare-ups of these diseases also the most common acute events (48.28% and 27.58%, respectively). Seven patients (24.14%) received liver transplants. At first admission, Acute-on-Chronic Liver Failure Research Consortium and Chronic Liver Failure-Sequential Organ Failure Assessment cut-off scores to predict liver transplant were 7.5 and 6.5; at end of day 5 or before transplant, cut-off scores were 8.5 and 7.5, respectively. The 8.5 cut-off score on day 5 was the most specific and sensitive to predict liver transplant. International normalized ratio cut-off of 3.04 predicted transplant requirement with maximum sensitivity and specificity. Wilson disease and autoimmune hepatitis were the most common underlying chronic and acute events of acute-on-chronic liver failure in children. Although an Acute-on-Chronic Liver Failure Research Consortium score ≥ 8.5 best predicted liver transplant, for patients with scores ≥ 7.5 and being followed in a nontransplant center, patient referral to a transplant center is appropriate.

Initial experience with high-volume plasma exchange in patients with acute liver failure.

High-volume plasma exchange (HVPE), defined as an exchange of 8 to 12 L per day per procedure or 15% of the ideal body weight with fresh frozen plasma, has shown promising results in improving the survival of patients with acute liver failure (ALF). However, clinical evidence is limited. The aim of this study was to report our initial experience using HVPE as a bridge treatment in patients with ALF. We retrospectively reviewed 32 consecutive patients awaiting liver transplantation (LT) due to ALF between 2013 and 2020 at Samsung Medical Center in Korea. HVPE has been used for patients with ALF since May 2016 at our institution. During the study period, 16 patients received HVPE. After HVPE, coagulopathies (INR, 4.46 [2.32-6.02] vs 1.48 [1.33-1.76], P < .05), total bilirubin (22.6 [9.1-26.4] vs 8.9 [5.6-11.3], P < .05), alanine aminotransferase (506 [341-1963] vs 120 [88-315], P < .05), and ammonia levels (130.6 [123.7-143.8] vs 98.2 [84.2-116.5], P < .05) were improved. Improvement in the hepatic encephalopathy grade was observed in four patients. Among 16 patients who received HVPE, 12 patients were bridged to LT, and three patients recovered spontaneously. The overall survival was 94% and 69%, respectively at 30 days in patients who received and did not receive HVPE (P =.068). Among 18 patients with high chronic liver failure-sequential organ failure assessment scores (≥13), the overall survival was significantly better for those who received HVPE than for those who did not (91% vs 29%, respectively, at 30 days, P < .05). Our initial clinical experience with HVPE suggests that HVPE can be a viable option in improving the outcomes of patients presenting with ALF.

Acute-on-chronic liver failure as a major predictive factor for mortality in patients with variceal bleeding

Background/AimsThis study examined the risk factors associated with mortality in cirrhotic patients hospitalized with variceal bleeding, and evaluated the effects of acute-on-chronic liver failure (ACLF) on the prognosis of these patients.MethodsThis study was retrospectively conducted on patients registered in the Korean acute-on-chronic liver failure study cohort, and on 474 consecutive cirrhotic patients hospitalized with variceal bleeding from January 2013 to December 2013 at 21 university hospitals. ACLF was defined as described by the European Association for the Study of Liver-Chronic Liver Failure Consortium.ResultsAmong a total of 474 patients, 61 patients were diagnosed with ACLF. The cumulative overall survival (OS) rate was lower in the patients with ACLF than in those without (P<0.001), and patients with higher ACLF grades had a lower OS rate (P<0.001). The chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score was identified as a significant prognostic factor in patients hospitalized with variceal bleeding (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.30–1.50; P<0.001), even in ACLF patients with variceal bleeding (HR, 1.32; 95% CI, 1.19–1.46, P<0.001). Concerning the prediction of the mortality risk at 28- and 90-day using CLIF-SOFA scores, c-statistics were 0.895 (95% CI, 0.829–0.962) and 0.897 (95% CI, 0.842–0.951), respectively, and the optimal cut-off values were 6.5 and 6.5, respectively.ConclusionsIn cirrhotic patients hospitalized with variceal bleeding, the prognosis was poor when accompanied by ACLF, especially depending upon CLIF-SOFA score. CLIF-SOFA model well predicted the 28-day or 90-day mortality for cirrhotic patients who experienced variceal bleeding.

Liver‐specific scores as predictors of mortality in spontaneous bacterial peritonitis

Background Liver-specific scores have been developed and are currently used to predict mortality in cirrhotic patients. The purpose of this study is to analyse and compare their ability to predict mortality in cirrhotic patients with spontaneous bacterial peritonitis. Design and setting Historical cohort study conducted in a public tertiary care teaching hospital. Methods 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 hand analysed and patients were included if they were over 18-year old, with cirrhosis and an ascites fluid compatible with spontaneous bacterial peritonitis. It was included 69 patients. Liver-specific scores were calculated and ROC curves pairwise comparisons were performed using DeLong test. Results Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) was able to predict mortality in 30, 90 and 365 days, with AUROC of 0.75, 0.64 and 0.64 respectively. Values of CLIF-SOFA above 5 was able to predict higher mortality for all patients, with sensitivity of 87%, 74% and 56% and specificity of 52%, 46% and 66% for 28-, 90- and 365-day mortality respectively (P < .05). CLIF-SOFA was able to predict mortality in every time frame for all patients and acute-on-chronic liver failure (ACLF) patients. CLIF-SOFA values above 7 were associated with higher mortality for ACLF patients. Conclusion CLIF-SOFA score was superior to other liver-specific scores for predicting mortality in a cohort of cirrhotic patients admitted due to spontaneous bacterial peritonitis in a teaching hospital in Brazil.

Leucocyte ratios are biomarkers of mortality in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure.

In patients with cirrhosis, progression to acute decompensation (AD) and acute-on-chronic liver failure (ACLF) has been associated with poor prognosis. Differential leucocyte ratios might predict mortality in systemic inflammatory conditions. To evaluate differential leucocyte ratios as prognostic biomarkers in patients with cirrhosis. Patients with AD and ACLF were recruited from four centres in three countries. Peripheral blood differential leucocytes were measured (three centres using flow cytometry) on hospital admission and at 48 hours. Ratios were correlated to model for end-stage liver disease (MELD), chronic liver failure-sequential organ failure (CLIF-SOFA), suspected/culture-positive bacterial infection and survival. Nine hundred twenty-six patients (562 (61%) male, median age 55 (25-94) years) were studied. Overall, 350 (37%) did not survive to hospital discharge. Neutrophil-lymphocyte ratio (NLR) and monocyte-lymphocyte ratio (MLR) were elevated in patients with AD and ACLF who died during their hospital stay. On multivariate analysis NLR retained statistical significance independently of CLIF-SOFA or MELD. NLR >30 was associated with an 80% 90-day mortality in patients with ACLF but not AD. On sensitivity analysis for subgroups (alcohol-related liver disease and suspected sepsis), NLR and MLR retained statistically robust accuracy for the prediction of mortality. Significant predictive accuracy was only observed in centres using flow cytometry. Leucocyte ratios are simple and robust biomarkers of outcome in ACLF, which are comparable to CLIF-SOFA score but dependent on leucocyte quantification method. NLR and MLR may be used as screening tools for mortality prediction in patients with acutely deteriorating cirrhosis.

Empirical Treatment With Carbapenem vs Third-generation Cephalosporin for Treatment of Spontaneous Bacterial Peritonitis

Third-generation cephalosporins (TGCs) are recommended as first-line antibiotics for treatment of spontaneous bacterial peritonitis (SBP). However, antibiotics against multidrug-resistant organisms (such as carbapenems) might be necessary. We aimed to evaluate whether carbapenems are superior to TGC for treatment of SBP. We performed a retrospective study of 865 consecutive patients with a first presentation of SBP (275 culture positive; 103 with TGC-resistant bacterial infections) treated at 7 referral centers in Korea, from September 2013 through January 2018. The primary outcome was in-hospital mortality. We made all comparisons using data from patients whose baseline characteristics were balanced by inverse probability of treatment weighting. Of patients who initially received empirical treatment with antibiotics, 95 (11.0%) received carbapenems and 655 (75.7%) received TGCs. Among the entire study cohort, there was no significant difference in in-hospital mortality between the carbapenem (25.8%) and TGC (25.3%) groups (adjusted odds ratio [aOR], 0.97; 95% CI, 0.85-1.11; P = .66). In the subgroup of patients with high chronic liver failure-sequential organ failure assessment (CLIF-SOFA) scores (score of 7 or greater, n = 314), carbapenem treatment was associated with lower in-hospital mortality (23.1%) than in the TGC group (38.8%) (aOR, 0.84; 95% CI, 0.75-0.94; P=.002). In contrast, among patients with lower CLIF-SOFA scores (n = 436), in-hospital mortality did not differ significantly between the carbapenem group (24.7%) and the TGC group (16.0%) (aOR, 1.06; 95% CI, 0.85-1.32; P = .58). For patients with a first presentation of SBP, empirical treatment with carbapenem does not reduce in-hospital mortality compared to treatment with TGCs. However, among critically ill patients (CLIF-SOFA scores ≥7), empirical carbapenem treatment was significantly associated with lower in-hospital mortality than TGCs.