Persistent or incident hyperammonemia is associated with poor outcomes in acute decompensation and acute-on-chronic liver failure.
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ABSTRACT:
SUBMITTER: Shalimar
PROVIDER: S-EPMC7578315 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
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Persistent or incident hyperammonemia is associated with poor outcomes in acute decompensation and acute-on-chronic liver failure.
Shalimar Rout Gyanranjan G Kumar Ramesh R Singh Achintya D AD Sharma Sanchit S Gunjan Deepak D Saraya Anoop A Nayak Baibaswata B Acharya Subrat K SK
JGH open : an open access journal of gastroenterology and hepatology 20200228 5
<h4>Background and aim</h4>The effect of elevated ammonia on organ failures (OF), apart from hepatic encephalopathy, in patients with acute decompensation (AD) of cirrhosis and acute-on-chronic liver failure (ACLF) is unclear. We aimed to assess the effect of persistent or incident hyperammonemia on OF and outcomes in patients with AD and ACLF.<h4>Methods</h4>A total of 229 patients with ACLF and 83 with AD were included. Arterial ammonia was measured on day 1 and day 3 of admission. Persistent ...[more]
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Project description:To validate prognostic scores for acute decompensation of cirrhosis and acute-on-chronic liver failure in Brazilian patients.This is a prospective cohort study designed to assess the prognostic performance of the chronic liver failure-consortium (CLIF-C) acute decompensation score (CLIF-C AD) and CLIF-C acute-on-chronic liver failure score (CLIF-C ACLF), regarding 28-d and 90-d mortality, as well as to compare them to other prognostic models, such as Model for End-Stage Liver Disease (MELD), MELD Sodium (MELD-Na), Child-Pugh (CP) score, and the CLIF-C Organ Failure score (CLIF-C OF). All participants were adults with acute decompensation of cirrhosis admitted to the Emergency Department of a tertiary hospital in southern Brazil. Prognostic performances were evaluated by means of the receiver operating characteristic (ROC) curves, area under the curves (AUC) and 95%CI.One hundred and thirteen cirrhotic patients were included. At admission, 18 patients had acute-on-chronic liver failure (ACLF) and 95 individuals had acute decompensation (AD) without ACLF, of which 24 eventually developed ACLF during the course of hospitalization (AD evolving to ACLF group). The AD group had significantly lower 28-d (9.0%) and 90-d (18.3%) mortality as compared to the AD evolving to ACLF group and to the ACLF group (both P < 0.001). On the other hand, 28-d and 90-d mortalities were not significantly different between AD evolving to ACLF group and ACLF group (P = 0.542 and P = 0.708, respectively). Among patients with ACLF, at 28 d from the diagnosis, CLIF-C ACLF was the only score able to predict mortality significantly better than the reference line, with an AUC (95%CI) of 0.71 (95%CI: 0.54-0.88, P = 0.021). Among patients with AD, all prognostic scores performed significantly better than the reference line regarding 28-d mortality, presenting with similar AUCs: CLIF-C AD score 0.75 (95%CI: 0.63-0.88), CP score 0.72 (95%CI: 0.59-0.85), MELD score 0.75 (95%CI: 0.61-0.90), MELD-Na score 0.76 (95%CI: 0.61-0.90), and CLIF-C OF score 0.74 (95%CI: 0.60-0.88). The same occurred concerning AUCs for 90-d mortality: CLIF-C AD score 0.70 (95%CI: 0.57-0.82), CP score 0.73 (95%CI: 0.62-0.84), MELD score 0.71 (95%CI: 0.59-0.83), MELD-Na score 0.73 (95%CI: 0.62-0.84), and CLIF-C OF score 0.65 (95%CI: 0.52-0.78).This study demonstrated that CLIF-C ACLF is the best available score for the prediction of 28-d mortality among patients with ACLF. CLIF-C AD score is also useful for the prediction of mortality among cirrhotic patients with AD not fulfilling diagnostic criteria for ACLF, but it was not superior to other well-established prognostic scores.
| S-EPMC5537190 | biostudies-other
Project description:It is essential to identify the subgroup of patients who experience poorer outcomes in order to adapt clinical management effectively. In the context of liver disease, the earlier the identification occurs, the greater the range of therapeutic options that can be offered to patients. In the past, patients with acute decompensation (AD) of chronic liver disease were treated as a homogeneous group, with emphasis on identifying those at the highest risk of death. In the last 15 years, a differentiation has emerged between acute-on-chronic liver failure syndrome (ACLF) and AD, primarily due to indications that the latter is linked to a less favorable short-term prognosis. Nevertheless, the definition of ACLF varies among the different knowledge societies, making it challenging to assess its true impact compared with AD. Therefore, the purpose of this review is to provide a detailed analysis emphasizing the critical importance of identifying ACLF in the field of advanced liver disease. We will discuss the differences between Eastern and Western approaches, particularly in relation to the occurrence of liver failure and disease onset. Common characteristics, such as the dynamic nature of the disease course, will be highlighted. Finally, we will focus on two key clinical implications arising from these considerations: the prevention of ACLF before its onset and the clinical management strategies once it develops, including liver transplantation and withdrawal of care.
| S-EPMC10954432 | biostudies-literature
Project description:BACKGROUNDAcute-on-chronic liver failure (ACLF) is characterized by the presence of acute decompensation (AD) of cirrhosis, organ failure, and high short-term mortality rates. Hemodynamic dysfunction and activation of endogenous vasoconstrictor systems are thought to contribute to the pathogenesis of ACLF. We explored whether copeptin, a surrogate marker of arginine vasopressin, is a potential marker of outcome in patients admitted for AD or ACLF and whether it might be of additional value to conventional prognostic scoring systems in these patients.METHODSAll 779 patients hospitalized for AD of cirrhosis from the CANONIC database with at least one serum sample available for copeptin measurement were included. Presence of ACLF was defined according to the CLIF-consortium organ failure (CLIF-C OF) score. Serum copeptin was measured in samples collected at days 0-2, 3-7, 8-14, 15-21, and 22-28 when available. Competing-risk regression analysis was applied to evaluate the impact of serum copeptin and laboratory and clinical data on short-term survival.RESULTSSerum copeptin concentration was found to be significantly higher in patients with ACLF compared with those without ACLF at days 0-2 (33 (14-64) vs. 11 (4-26) pmol/L; p?<?0.001). Serum copeptin at admission was shown to be a predictor of mortality independently of MELD and CLIF-C OF scores. Moreover, baseline serum copeptin was found to be predictive of ACLF development within 28 days of follow-up.CONCLUSIONSACLF is associated with significantly higher serum copeptin concentrations at hospital admission compared with those with traditional AD. Copeptin is independently associated with short-term survival and ACLF development in patients admitted for AD or ACLF.
| S-EPMC5740749 | biostudies-literature
Project description:IntroductionRecently, based on data from the PREDICT study, the European Foundation for the Study of Chronic Liver Failure (EF-CLIF) consortium proposed pathophysiological/prognostic groups in hospitalized patients with cirrhosis: stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre-acute-on-chronic liver failure (pre-ACLF), and ACLF. We evaluated the outcomes of these subgroups in a real-life cohort of hospitalized patients with cirrhosis.MethodsPatients with cirrhosis developing first AD between 09/2010 and 12/2017 at the Vienna General Hospital were evaluated for this retrospective analysis.ResultsTwo hundred and ten patients with cirrhosis (aged 57.6 ± 11.8 years) including n = 45 (21.4%) SDC, n = 100 (47.6%) UDC, n = 28 (13.3%) pre-ACLF, and n = 37 (17.6%) with ACLF were considered. The proposed AD subgroups discriminated between patients with favorable (1-year mortality: SDC: 6.7% and UDC: 19.6%) and dismal prognosis (90-day mortality: pre-ACLF: 42.9%). Interestingly, systemic inflammation gradually increased (e.g., C-reactive protein, SDC: 0.9 mg/dl, vs. UDC: 2.0 mg/dl vs. pre-ACLF: 3.2 mg/dl, p < 0.001) while renal function was progressively deteriorating (creatinine levels, SDC: 0.8 mg/dl vs. UDC: 0.9 mg/dl vs. pre-ACLF: 1.2 mg/dl, p < 0.001) across prognostic subgroups in patients with cirrhosis.DiscussionThe recently proposed pathophysiological/prognostic EF-CLIF subgroups are also reproduceable in a real-life cohort of cirrhotic patients. As ACLF is a common and important complication, patients at risk of pre-ACLF at index AD should be evaluated and if disease proceeds, been treated early and aggressively to avoid excessive mortality.
| S-EPMC8259248 | biostudies-literature
Project description:BackgroundHepatic encephalopathy (HE) is a common feature of acute liver failure and has been reported to be associated with poor outcomes. Ammonia is thought to be central to the pathogenesis of HE, but its role in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is unclear. The present study aimed to assess the prognostic role of ammonia level for patients with HBV-ACLF.MethodsWe retrospectively recruited 127 patients diagnosed with HBV-ACLF for the present study.ResultsAmmonia levels at the time of admission were higher among non-surviving participants than in survivors. Increased ammonia level was found to be associated with severe liver disease and was identified as an independent predictor for mortality in patients with HBV-ACLF.ConclusionsOur results suggest that high ammonia level at admission is an independent factor for predicting short-term mortality in patients with HBV-ACLF. Therefore, ammonia levels may represent a therapeutic target for this condition.
| S-EPMC7755815 | biostudies-literature
Project description:Nosocomial acute-on-chronic liver failure (nACLF) develops in at least 10% of patients with cirrhosis hospitalized for acute decompensation (AD), greatly worsening their prognosis. In this prospective observational study, we aimed to identify rapidly obtainable predictors at admission, which allow for the early recognition and stratification of patients at risk of nACLF. Methods:A total of 516 consecutive patients hospitalized for AD of cirrhosis were screened: those who did not present ACLF at admission (410) were enrolled and surveilled for the development of nACLF. Results:Fifty-nine (14%) patients developed nALCF after a median of 7 (IQR 4-18) days. At admission, they presented a more severe disease and higher degrees of systemic inflammation and anemia than those (351; 86%) who remained free from nACLF. Competing risk multivariable regression analysis showed that baseline MELD score (sub-distribution hazard ratio [sHR] 1.15; 95% CI 1.10-1.21; p ?0.001), hemoglobin level (sHR 0.81; 95% CI 0.68-0.96; p = 0.018), and leukocyte count (sHR 1.11; 95% CI 1.06-1.16; p ?0.001) independently predicted nACLF. Their optimal cut-off points, determined by receiver-operating characteristic curve analysis, were: 13 points for MELD score, 9.8 g/dl for hemoglobin, and 5.6x109/L for leukocyte count. These thresholds were used to stratify patients according to the cumulative incidence of nACLF, being 0, 6, 21 and 59% in the presence of 0, 1, 2 or 3 risk factors (p ?0.001). Nosocomial bacterial infections only increased the probability of developing nACLF in patients with at least 1 risk factor, rising from 3% to 29%, 16% to 50% and 52% to 83% in patients with 1, 2 or 3 risk factors, respectively. Conclusions:Easily available laboratory parameters, related to disease severity, systemic inflammation, and anemia, can be used to identify, at admission, hospitalized patients with AD at increased risk of developing nACLF. Lay summary:More than 10% of patients with cirrhosis hospitalized because of an acute decompensation develop acute-on-chronic liver failure, which is associated with high short-term mortality, during their hospital stay. We found that the combination of 3 easily obtainable variables (model for end-stage liver disease score, leukocyte count and hemoglobin level) help to identify and stratify patients according to their risk of developing nosocomial acute-on-chronic liver failure, from nil to 59%. Moreover, if a nosocomial bacterial infection occurs, such an incidence proportionally increases from nil to 83%. This simple approach helps to identify patients at risk of developing nosocomial acute-on-chronic liver failure at admission to hospital, enabling clinicians to put in place preventive measures.
| S-EPMC7001573 | biostudies-literature
Project description:Background & aimsHuman allogeneic liver-derived progenitor cells (HALPC, HepaStem®; Promethera Biosciences, Mont-Saint-Guibert, Belgium) are an advanced therapy medicinal product that could potentially alleviate systemic inflammation and ameliorate liver function in patients with acute-on-chronic liver failure (ACLF) or acute decompensation of cirrhosis (AD).MethodsThis open-label phase II study was conducted in 9 centres in Belgium, Spain, and Bulgaria between 2016 and 2019. The primary objective was to assess the safety of HALPC therapy up to Day 28 and the secondary objectives were to assess its safety and preliminary efficacy up to Month 3.ResultsThe 24 treated patients (mean age: 51 years) were mostly male with an alcoholic cirrhosis. On pre-infusion Day 1, 15 patients had ACLF and 9 patients had AD. Two of the 3 initial patients treated with high HALPC doses (∼5×106 cells/kg body weight [BW]) had severe adverse bleeding events attributed to treatment. In 21 patients subsequently treated with lower HALPC doses (0.6 or 1.2×106 cells/kg BW, 1 or 2 times 7 days apart), no serious adverse events were related to treatment, and the other adverse events were in line with those expected in patients with ACLF and AD. Overall, markers of systemic inflammation and altered liver function decreased gradually for the surviving patients. The Day-28 and Month-3 survival rates were 83% (20/24) and 71% (17/24), and at Month 3, no patient had ACLF.ConclusionsThe treatment of patients with ACLF or AD with up to 2 doses of 1.2×106 HALPC/kg BW appeared safe. The results of this study support the initiation of a proof-of-concept study in a larger cohort of patients with ACLF to further confirm the safety and evaluate the efficacy of HALPC therapy.Clinical trials registrationEudraCT 2016-001177-32.Lay summaryPatients with liver cirrhosis may suffer from the rapid onset of organ failure or multiple organ failure associated with a high risk of death in the short term. This clinical study of 24 patients suggests that an advanced therapy based on the intravenous infusion of low doses of human allogeneic liver-derived progenitor cells is safe and supports the next phase of clinical development of this type of therapy.
| S-EPMC8207211 | biostudies-literature
Project description:Background & aimsUnderstanding factors responsible for the increased bleeding tendency in acute-on-chronic liver failure (ACLF) would improve the management of these complications. We investigated coagulation alterations in ACLF and assessed whether they were predictive of bleeding.MethodsCirrhosis patients with ACLF (cases) and acute decompensation (AD, controls) were prospectively recruited and underwent an extensive haemostatic assessment including standard tests, pro and anticoagulant factors, thrombomodulin-modified thrombin generation (TG) and thromboelastometry (ROTEM® ). In study part 1 (case-control), we compared coagulation in ACLF vs AD. In study part 2 (prospective), all patients were followed for bleeding, and predictors of outcome were assessed.ResultsNinety-one patients were included (51 with ACLF, 40 with AD). Infections and ascites/renal dysfunction were the most common precipitating and decompensating events. Platelet count was lower while INR and activated partial thrombin time were longer in ACLF cohort vs AD. Regarding clotting factors, fibrinogen and factor VIII were comparable between groups while protein C and antithrombin were significantly reduced in ACLF. Endogenous thrombin potential by TG was comparable between groups. Clotting formation time and clot stability by ROTEM® were significantly lower in ACLF, indicative of a more hypocoagulable state. No haemostasis alteration could discriminate between patients who had bleeding complications during hospitalization and those who did not.ConclusionWe found coagulation changes in ACLF to largely overlap with that of AD and evidence of preserved coagulation capacity in both groups. ROTEM alterations were indicative of a more pronounced hypocoagulable state in ACLF; however, no correlation was found between such alterations and bleeding.
| S-EPMC8518681 | biostudies-literature
Project description:BackgroundAcute decompensation (AD) of liver cirrhosis (LC) and subsequent acute-on-chronic liver failure (ACLF) are fatal and impair quality of life. Insufficient knowledge of the highly heterogeneous natural history of LC, including decompensation, re-compensation, and possible recurrent decompensation, hinders the development and application of novel therapeutics. Approximately 10%-50% of AD/ACLF is reported to be precipitated by any indeterminate (unidentifiable, cryptogenic, or unknown) acute insults; however, its clinical characteristics are unclear.MethodsWe conducted a single-center observational study of 2165 consecutively admitted patients with LC from January 2012 to December 2019. A total of 466 episodes of AD/ACLF in 285 patients, including their 285 first indexed AD/ACLF, were extracted for analysis. Stratified analyses of different acute precipitants, classified as indeterminate (AD/ACLFIND), bacterial infection (AD/ACLFBAC), gastrointestinal bleeding, active alcoholism, and miscellaneous, were performed.ResultsAD/ACLFIND was the leading acute precipitant (28%), followed by AD/ACLFBAC (23%). AD/ACLFIND showed better survival outcomes than AD/ACLFBAC (P = 0.03); however, hyperbilirubinemia, hyponatremia, or leukocytosis significantly and uniquely characterized subgroups of AD/ACLFIND with comparable or even worse survival outcomes than those of AD/ACLFBAC. Patients with subsequent AD/ACLF significantly tended to suffer from AD/ACLF with any organ failure in AD/ACLFIND but not in AD/ACLFBAC (P = 0.004, for trend). In competing risk analysis, patients with AD/ACLFIND were significantly more vulnerable to suffer from recurrent episodes of AD/ACLF within 180 days, compared to those triggered by other precipitants (P = 0.04).ConclusionsAD/ACLFIND, the leading acute precipitant, also plays a role in subsequent AD/ACLF. An abruptly exacerbating, remitting, and relapsing nature of systemic inflammation underlying AD/ACLF may also be useful for risk estimation.
| S-EPMC8043384 | biostudies-literature
Project description:Over the past 2 decades, the concept of acute-on-chronic liver failure (ACLF) has been proposed as an alternate path in the natural history of decompensated cirrhosis. ACLF thus is characterized by the presence of a precipitating event (identified or unidentified) in subjects with underlying chronic liver disease leading to rapid progression of liver injury and ending in multi-organ dysfunction characterized by high short-term mortality. Multiple organ failure and an increased risk for mortality are key to the diagnosis of ACLF. The prevalence of ACLF ranges from 24% to 40% in hospitalized patients. The pathophysiological basis of ACLF can be explained using the following 4-part model: predisposing event, injury caused by a precipitating event, response to injury, and organ failure. Although several mathematic scores have been proposed for identifying outcomes with ACLF, it is as yet unclear whether these organ failure scores are truly prognostic or only reflective of the dying process. Treatment paradigms continue to evolve but consist of early recognition, supportive intensive care, and consideration of liver transplantation before onset of irreversible multiple organ failure.
| S-EPMC4625547 | biostudies-literature