Dataset Information

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

ABSTRACT:

Background and aim

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.

Methods

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 or incident hyperammonemia was defined as a level of ≥79.5 μmol/L on day 3. The changes in ammonia levels during the first 3 days were analyzed with respect to the complications and outcomes.

Results

At admission, the median level of arterial ammonia was higher in ACLF compared to AD patients (103 vs 86 μmol/L, P < 0.001). Persistent or incident hyperammonemia was noted in 206 (66.0%) patients and was more frequent in ACLF compared to AD patients (70.7 vs 53.0%, P = 0.013). Patients with persistent or incident hyperammonemia, compared to those without it, developed a higher proportion of new-onset OF during hospitalization involving liver (P = 0.018), kidney (P = 0.001), brain (P = 0.005), coagulation (P = 0.036), circulation (P = 0.002), and respiratory (P = 0.003) issues and had higher 28-day mortality (log-rank test, P < 0.001). After adjustment for chronic liver failure consortium ACLF score, persistent or incident hyperammonemia (hazard ratio, 3.174) was independently associated with 28-day mortality. The presence of infection was an independent predictor of persistent or incident hyperammonemia.

Conclusion

Persistent or incident hyperammonemia during first 3 days of hospitalization in patients with AD or ACLF is associated with increased risk of OF and death.

SUBMITTER: Shalimar

PROVIDER: S-EPMC7578315 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

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]

PMID: 33102753

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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.

Project description:Background & objectivesCirrhosis patients with worsening of the liver function are defined as acute decompensation (AD) and those who develop extrahepatic organ failure are defined as acute-on-chronic liver failure (ACLF). Both AD and ACLF have an extremely poor prognosis. However, information regarding prognostic predictors is still lacking in Asian populations. We aimed to identify prognostic factors for 30-day and 90-day mortality in cirrhosis patients who develop AD with or without ACLF.MethodsWe included 9 tertiary hospitals from Thailand in a retrospective observational study enrolling hospitalized cirrhosis patients with AD. ACLF was diagnosed according to the EASL-CLIF criteria, which defined as AD patients who have kidney failure or a combination of at least two non-kidney organ failure. Outcomes were clinical parameters and prognostic scores associated with mortality evaluated at 30 days and 90 days.ResultsBetween 2015 and 2020, 602 patients (301 for each group) were included. The 30-day and 90-day mortality rates of ACLF vs. AD were 57.48% vs. 25.50% (p<0.001) and 67.44% vs. 32.78% (p<0.001), respectively. For ACLF patients, logistic regression analysis adjusted for demographic data, and clinical information showed that increasing creatinine was a predictor for 30-day mortality (p = 0.038), while the CLIF-C OF score predicted both 30-day (p = 0.018) and 90-day (p = 0.037) mortalities, achieving the best discriminatory power with AUROCs of 0.705 and 0.709, respectively. For AD patients, none of the parameters was found to be significantly associated with 30-day mortality, while bacterial infection, CLIF-AD score and Child-Turcotte-Pugh score were independent parameters associated with 90-day mortality, with p values of 0.041, 0.024 and 0.024. However, their predictive performance became nonsignificant after adjustment by multivariate regression analysis.ConclusionsRegarding Thai patients, the CLIF-C OF score was the best predictor for 30-day and 90-day mortalities in ACLF patients, while appropriate prognostic factors for AD patients remained inconclusive.

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.

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.

Dataset Information

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

Background and aim

Methods

Results

Conclusion

Publications

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

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