Frailty and Sarcopenia in Acute-on-Chronic Liver Failure.
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ABSTRACT:
SUBMITTER: Puchades Renau L
PROVIDER: S-EPMC8369934 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAcute-on-chronic liver failure (ACLF) is characterized by the development of a syndrome associated with a high risk of short-term death in patients with acute decompensated cirrhosis, and better indicators are needed to predict such outcomes. Sarcopenia, a common complication of cirrhosis, is closely associated with poor prognosis and increased mortality. In this study, the skeletal muscle index of ACLF patients was measured to determine whether sarcopenia combined with clinical parameters can aid in identifying those at high risk of progression.MethodsA total of 433 hospitalized patients with ACLF according to the APASL criteria were included and allocated into two groups: transplantation-free survival (n = 293) or progression (n = 140, 107 died; 33 underwent liver transplantation) within 90 days. Muscle mass was assessed based on the skeletal muscle index. The optimal cut-off value of the AMPAS1 model (age, MELD score, platelet count, alpha-fetoprotein level, sarcopenia, and more than one complication combination) for progression prediction was identified using receiver-operating characteristic (ROC) analysis.ResultsSarcopenia was an independent risk factor for progression in the ACLF population (HR 3.771 95% CI 2.114-6.727, p < 0.001). AMPAS1 was a good predictor, with an area under the ROC curve of 0.865, and the cut-off value for poor outcome prediction was 0.31 (sensitivity 79.4%, specificity 76.4%).ConclusionWe demonstrate that sarcopenia is a simple and objective indicator for predicting short-term prognosis in patients with ACLF. Moreover, compared to conventional prognostic scores, AMPAS1 is a better model for predicting 90 day adverse outcomes in ACLF patients.
| S-EPMC9349113 | 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
Project description:There is significant interest in identifying risk factors associated with acute-on-chronic liver failure (ACLF). In transplant candidates, frailty predicts wait-list mortality and posttransplant outcomes. However, the impact of frailty on ACLF development and mortality is unknown. This was a retrospective study of US veterans with cirrhosis identified between 2008 and 2016. First hospitalizations were characterized as ACLF or non-ACLF admissions. Prehospitalization patient frailty was ascertained using a validated score based on administrative coding data. We used logistic regression to investigate the impact of an increasing frailty score on the odds of ACLF hospitalization and short-term ACLF mortality. Cox regression was used to analyze the association between frailty and longterm survival from hospitalization. We identified 16,561 cirrhosis hospitalizations over a median follow-up of 4.19 years (interquartile range, 2.47-6.34 years). In adjusted models, increasing frailty score was associated with significantly increased odds of ACLF hospitalization versus non-ACLF hospitalization (odds ratio, 1.03 per point; 95% CI 1.02-1.03; P < 0.001). By contrast, frailty score was not associated with ACLF 28- or 90-day mortality (P = 0.13 and P = 0.33, respectively). In an adjusted Cox analysis of all hospitalizations, increasing frailty scores were associated with poorer longterm survival from the time of hospitalization (hazard ratio, 1.02 per 5 points; 95% confidence interval, 1.01-1.03; P = 0.004). Frailty increases the likelihood of ACLF hospitalization among patients with cirrhosis, but it does not impact short-term ACLF mortality. These findings have implications for clinicians caring for frail outpatients with cirrhosis, including tailored follow-up, risk mitigation strategies, and possible expedited transplant evaluation.
| S-EPMC8249075 | biostudies-literature
Project description:INTRODUCTION:Muscle mass has been shown to be a prognostic marker in patients with liver cirrhosis. Transversal psoas muscle thickness normalized by height (TPMT/height) obtained by routine computed tomography is a simple surrogate parameter for sarcopenia. TPMT/height, however, is not sex specific, which might play a role in risk stratification. Its association with acute-on-chronic liver failure (ACLF) has not been established yet. ACLF is associated with systemic inflammatory dysregulation. This study aimed at evaluating the role of sarcopenia in ACLF development of patients with decompensated cirrhosis receiving transjugular intrahepatic portosystemic shunt (TIPS) using sex-specific TPMT/height. METHODS:One hundred eighty-six patients from the prospective Non-invasive Evaluation Program for TIPS and Follow Up Network cohort (observational, real-world TIPS cohort with structured follow-up) were analyzed. TPMT/height was measured from routine computed tomography. The sex-specific cutoff was determined to classify patients as sarcopenic and nonsarcopenic for 1-year mortality after TIPS. Clinical outcome was compared. Primary end points were ACLF and 1-year mortality after TIPS. Secondary end points were development of decompensations (hepatic encephalopathy and ascites) after TIPS. RESULTS:The sex-specific cutoff increases the diagnostic accuracy with regard to primary and secondary end points compared with the unisex cutoff. Sex-specific sarcopenia classification is an independent predictor of 1-year mortality and ACLF development in patients with cirrhosis receiving TIPS. Patients in the sarcopenia group showed significantly higher rates of mortality, ascites, overt hepatic encephalopathy, and ACLF after TIPS compared with the nonsarcopenia group. The Chronic Liver Failure Consortium Acute Decompensation score as a marker of systemic inflammation was significantly higher in sarcopenic patients. CONCLUSIONS:This study demonstrates for the first time that sarcopenia is related to ACLF development and systemic inflammation. The prognostic value of TPMT/height can be improved by using sex-specific cutoffs. ClinicalTrials.gov identifier: NCT03584204.
| S-EPMC6602782 | biostudies-literature
Project description:Sarcopenia and frailty are geriatric syndromes characterized by multisystem decline, which are related to and reflected by markers of skeletal muscle dysfunction. In older people, sarcopenia and frailty have been used for risk stratification, to predict adverse outcomes and to prompt intervention aimed at preventing decline in those at greatest risk. In this review, we examine sarcopenia and frailty in the context of chronic respiratory disease, providing an overview of the common assessments tools and studies to date in the field. We contrast assessments of sarcopenia, which consider muscle mass and function, with assessments of frailty, which often additionally consider social, cognitive and psychological domains. Frailty is emerging as an important syndrome in respiratory disease, being strongly associated with poor outcome. We also unpick the relationship between sarcopenia, frailty and skeletal muscle dysfunction in chronic respiratory disease and reveal these as interlinked but distinct clinical phenotypes. Suggested areas for future work include the application of sarcopenia and frailty models to restrictive diseases and population-based samples, prospective prognostic assessments of sarcopenia and frailty in relation to common multidimensional indices, plus the investigation of exercise, nutritional and pharmacological strategies to prevent or treat sarcopenia and frailty in chronic respiratory disease.
| S-EPMC5720213 | biostudies-literature
Project description:BackgroundFrailty, characterized by vulnerability, reduced reserves and increased susceptibility to severe events, is a significant concern in chronic haemodialysis (HD) patients. Sarcopenia, corresponding to the progressive loss of muscle mass and strength, may contribute to frailty by reducing functional capacity, mobility and autonomy. However, consensus lacks on the optimal bedside frailty index for chronic HD patients. This study investigated the influence of frailty on chronic HD patient survival and explored the associated factors.MethodsA total of 135 patients were enrolled from January to April 2019 and then followed up prospectively until April 2022. At inclusion, frailty was assessed by the Timed Up and Go (TUG) and Short Physical Performance Battery (SPPB) tests including gait speed, standing balance and lower limb muscle strength.ResultsFrom a total of 114 prevalent chronic HD patients (66% men, age 67.6 ± 15.1 years), 30 died during the follow-up period of 23.7 months (range 16.8-34.3). Deceased patients were older, had more comorbidities and a higher sarcopenia prevalence (P < .05). The TUG and SPPB test scores were significantly reduced in patients who had died [SPPB total score: 7.2 ± 3.3 versus 9.4 ± 2.5; TUG time 8.7 ± 5.8 versus 13.8 ± 10.5 (P < .05)]. Multivariate analysis showed that a higher SPPB score (total value >9) was associated with a lower mortality risk [hazard ratio 0.83 (95% confidence interval 0.74-0.92); P < .03). Each component of the SPPB test was also associated with mortality in univariate analysis, but only the SPPB balance test remained protective against mortality in multivariate analysis. Older age, lower handgrip strength and lower protein catabolic rate were associated with SPPB total scores <9, SPPB balance score and TUG time >10 s.ConclusionsScreening for frailty is crucial in chronic HD patients, and incorporating SPPB, especially the balance test, provides valuable insights. Diminished muscle strength and inadequate protein intake negatively influence the SPPB score and balance in chronic HD patients. Effective identification and management of frailty can therefore improve outcomes.Clinical trial registration clinicaltrialsgovNCT03845452.
| S-EPMC11231581 | biostudies-literature
Project description:Acute-on-chronic liver failure (ACLF) is a syndrome that develops in patients with acutely decompensated chronic liver disease. It is characterised by high 28-day mortality, the presence of one or more organ failures (OFs) and a variable but severe grade of systemic inflammation. Despite the peculiarity of each one, every definition proposed for ACLF recognizes it as a proper clinical entity. In this paper, we provide an overview of the diagnostic criteria proposed by the different scientific societies and the clinical characteristics of the syndrome. Established and experimental treatments are also described. Among the former, the most relevant are directed to support organ failures, treat precipitating factors and carry out early assessment for liver transplantation (LT). Further studies are needed to better clarify pathophysiology of the syndrome and discover new therapies.
| S-EPMC8509281 | biostudies-literature
Project description:BackgroundIncreasing evidence reveals a close and reciprocal link between acute-on-chronic liver failure (ACLF) and immunodysfunction.MethodsA literature search in PubMed and abstract databases of relevant congresses was performed.ResultsImportant characteristics of liver cirrhosis like tissue hypoxia, cell death, or bacterial translocation maintain a state of chronic inflammation. Precipitating events of ACLF such as infections or alcoholic hepatitis are capable of strongly augmenting cirrhosis-associated systemic inflammation to grades sufficient to induce ACLF-defining organ failures. Chronic systemic inflammation, however, is causally linked to profound immunosuppression. As a consequence, patients with liver cirrhosis and in particular with ACLF are at high risk for severe infections. Promising strategies to ameliorate immunodysfunction, like albumin substitution, administration of recombinant interleukin-22 or granulocyte colony-stimulating factor, antibiotic prophylaxis, or anticoagulation, are under development and offer the chance to specifically prevent and treat ACLF.ConclusionA better understanding of the immunopathology of ACLF will likely translate into the implementation of specific therapeutic modalities to prevent and overcome ACLF.
| S-EPMC6189545 | biostudies-literature
Project description:Acute-on-chronic liver failure (ACLF) is a clinical syndrome that occurs in patients with cirrhosis and is characterised by acute deterioration, organ failure and high short-term mortality. Alcohol is one of the leading causes of ACLF and the most frequently reported aetiology of underlying chronic liver disease. Among patients with alcoholic hepatitis (AH), ACLF is a frequent and severe complication. It is characterised by both immune dysfunction associated to an increased risk of infection and high-grade systemic inflammation that ultimately induce organ failure. Diagnosis and severity of ACLF determine AH prognosis, and therefore, ACLF prognostic scores should be used in severe AH with organ failure. Corticosteroids remain the first-line treatment for severe AH but they seem insufficient when ACLF is associated. Novel therapeutic targets to contain the excessive inflammatory response and reduce infection have been identified and are under investigation. With liver transplantation remaining one of the most effective therapies for severe AH and ACLF, adequate organ allocation represents a growing challenge. Hence, a clear understanding of the pathophysiology, clinical implications and management strategies of ACLF in AH is essential for hepatologists, which is narrated briefly in this review.
| S-EPMC9499845 | biostudies-literature
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