Acute-on-chronic liver failure as defined by the European (EASL-CLIF) versus North American (NACSELD) diagnostic criteria in their prediction of short-term prognosis in patients with decompensated cirrhosis admitted into hospital

2020 ◽  
Vol 73 ◽  
pp. S495
Author(s):  
Florence Wong ◽  
Rajender Reddy ◽  
Puneeta Tandon ◽  
Jennifer Lai ◽  
Nishita Jagarlamudi ◽  
...  
Keyword(s):  
Liver Failure ◽  
Diagnostic Criteria ◽  
North American ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure ◽  
Short Term

scholarly journals Acute-On-Chronic Liver Failure Defined by Asian Pacific Association for the Study of the Liver Should Include Decompensated Cirrhosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Manman Xu ◽  
Ming Kong ◽  
Pengfei Yu ◽  
Yingying Cao ◽  
Fang Liu ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Failure ◽  
Chronic Liver Disease ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure ◽  
Short Term ◽  
Asian Pacific ◽  
Long Term Mortality

Background and Aims: Acute-on-chronic liver failure (ACLF) is an acute deterioration of chronic liver disease with high short-term mortality. The inclusion or exclusion of previously decompensated cirrhosis (DC) in the diagnostic criteria of ACLF defined by the Asian Pacific Association for the Study of the Liver (APASL-ACLF) has not been conclusive. We aimed to evaluate the prognostic impact of decompensated cirrhosis in ACLF.Methods: We retrospectively collected a cohort of patients with a diagnosis of APASL-ACLF (with or without DC) hospitalized from 2012 to 2020 at three liver units in tertiary hospitals. Baseline characteristics and survival data at 28, 90, 180, 360, 540, and 720 days were collected.Results: Of the patients assessed using APASL-ACLF criteria without the diagnostic indicator of chronic liver disease, 689 patients were diagnosed with ACLF, of whom 435 had no decompensated cirrhosis (non-DC-ACLF) and 254 had previously decompensated cirrhosis (DC-ACLF). The 28-, 90-, 180-, 360-, 540-, and 720-day mortality were 24.8, 42.9, 48.7, 57.3, 63.4, and 68.1%, respectively, in DC-ACLF patients, which were significantly higher than in non-DC-ACLF patients (p < 0.05). DC was independently associated with long-term (180/360/540/720 days) but not short-term (28/90 days) mortality in patients with ACLF. Age, total bilirubin, international normalized ratio, and hepatic encephalopathy were independent risk factors for short- and long-term mortality risk in ACLF patients (p < 0.05).Conclusions: Patients with DC-ACLF have a higher mortality rate, especially long-term mortality, compared to non-DC-ACLF patients. Therefore, DC should be included in the diagnostic criteria of APASL-ACLF and treated according to the ACLF management process.

Development of diagnostic criteria and a prognostic score for hepatitis B virus-related acute-on-chronic liver failure

Gut ◽  
2017 ◽  
Vol 67 (12) ◽  
pp. 2181-2191 ◽  
Author(s):  
Tianzhou Wu ◽  
Jiang Li ◽  
Li Shao ◽  
Jiaojiao Xin ◽  
Longyan Jiang ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Liver Failure ◽  
Diagnostic Criteria ◽  
Prognostic Score ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Short Term ◽  
Hospitalised Patients ◽  
B Virus

ObjectiveThe definition of acute-on-chronic liver failure (ACLF) based on cirrhosis, irrespective of aetiology, remains controversial. This study aimed to clarify the clinicopathological characteristics of patients with hepatitis B virus-related ACLF (HBV-ACLF) in a prospective study and develop new diagnostic criteria and a prognostic score for such patients.DesignThe clinical data from 1322 hospitalised patients with acute decompensation of cirrhosis or severe liver injury due to chronic hepatitis B (CHB) at 13 liver centres in China were used to develop new diagnostic and prognostic criteria.ResultsOf the patients assessed using the Chronic Liver Failure Consortium criteria with the exception of cirrhosis, 391 patients with ACLF were identified: 92 with non-cirrhotic HBV-ACLF, 271 with cirrhotic HBV-ACLF and 28 with ACLF with cirrhosis caused by non-HBV aetiologies (non-HBV-ACLF). The short-term (28/90 days) mortality of the patients with HBV-ACLF were significantly higher than those of the patients with non-HBV-ACLF. Total bilirubin (TB) ≥12 mg/dL and an international normalised ratio (INR) ≥1.5 was proposed as an additional diagnostic indicator of HBV-ACLF, and 19.3% of patients with an HBV aetiology were additionally diagnosed with ACLF. The new prognostic score (0.741×INR+0.523×HBV-SOFA+0.026×age+0.003×TB) for short-term mortality was superior to five other scores based on both discovery and external validation studies.ConclusionsRegardless of the presence of cirrhosis, patients with CHB, TB ≥12 mg/dL and INR ≥1.5 should be diagnosed with ACLF. The new criteria diagnosed nearly 20% more patients with an HBV aetiology with ACLF, thus increasing their opportunity to receive timely intensive management.

scholarly journals A Prognostic Model of Acute-On-Chronic Liver Failure Based On Sarcopenia

2021 ◽  
Author(s):  
Hong Peng ◽  
Qian Zhang ◽  
Siyi Lei ◽  
Tingting Xiong ◽  
Li Long ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
High Risk ◽  
Liver Failure ◽  
Adverse Outcomes ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure ◽  
Short Term ◽  
Skeletal Muscle Index ◽  
Cutoff Value

Abstract Background Acute-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 biomarkers are needed to predict such outcomes. Sarcopenia, a common complication of cirrhosis, is tightly 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 helps in identifying those at high risk of progression. Methods A total of 314 hospitalized ACLF patients were included and allocated into groups of transplantation-free survival (n = 214) or progression (n = 100) within 90 days. Muscle mass was assessed based on the skeletal muscle index. The optimal cutoff value of the AMPAS1 model (age, MELD score, platelet count, alpha-fetoprotein level, sarcopenia and more than one complication combination) for progressive prediction was identified using receiver operating characteristic (ROC) analysis. Results Sarcopenia was an independent risk factor for progression in the ACLF population (HR 3.705 95%CI 2.131-6.441, P<0.001). AMPAS1 was a good predictor, with an area under the ROC curve of 0.908, and the cutoff value for poor outcome prediction was 0.21 (sensitivity 93.2%, specificity 71.1%). Conclusion We demonstrate that sarcopenia is a simple and objective biomarker for predicting short-term prognosis in patients with ACLF. Moreover, compared to conventional prognostic scores, AMPAS1 is a better model to predict 90-day adverse outcomes in ACLF patients.

scholarly journals Acute-on-Chronic Liver Failure: Pathophysiological Mechanisms and Management

2021 ◽  
Vol 8 ◽  
Author(s):  
Arshi Khanam ◽  
Shyam Kottilil
Keyword(s):  
Liver Failure ◽  
Fungal Infections ◽  
Chronic Liver ◽  
Definitive Treatment ◽  
Decompensated Cirrhosis ◽  
Variceal Hemorrhage ◽  
Chronic Liver Failure ◽  
Short Term ◽  
Pathophysiological Mechanisms ◽  
Short Term Mortality

Acute-on-chronic liver failure (ACLF) is a multifaceted condition with poor treatment options and high short-term mortality. ACLF can develop in patients with or without liver cirrhosis, where patients with decompensated cirrhosis display a higher risk of short-term mortality. Pathophysiological mechanisms include systemic inflammation due to bacterial and fungal infections and acute hepatic insult with drug, alcohol, and viral hepatitis. Cryptogenic factors also contribute to the development of ACLF. The clinical outcome of patients with ACLF gets further complicated by the occurrence of variceal hemorrhage, hepatorenal syndrome, hepatic encephalopathy, and systemic immune dysfunction. Regardless of the better understanding of pathophysiological mechanisms, no specific and definitive treatment is available except for liver transplantation. The recent approach of regenerative medicine using mesenchymal stem cells (MSCs) could be advantageous for the treatment of ACLF as these cells can downregulate inflammatory response by inducing antiinflammatory events and prevent hepatic damage and fibrosis by inhibiting hepatic stellate cell activation and collagen synthesis. Moreover, MSCs are involved in tissue repair by the process of liver regeneration. Considering the broad therapeutic potential of MSCs, it can serve as an alternative treatment to liver transplant in the near future, if promising results are achieved.

The Prediction of in‐Hospital Mortality in Decompensated Cirrhosis with Acute‐on‐Chronic Liver Failure

2021 ◽  
Author(s):  
Florence Wong ◽  
K Rajender Reddy ◽  
Puneeta Tandon ◽  
Jennifer C Lai ◽  
Nishita Jagarlamudi ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
Liver Failure ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure

scholarly journals Inhibition of glutamine synthetase in monocytes from patients with acute-on-chronic liver failure resuscitates their antibacterial and inflammatory capacity

Gut ◽  
2018 ◽  
Vol 68 (10) ◽  
pp. 1872-1883 ◽  
Author(s):  
Hannelie Korf ◽  
Johannie du Plessis ◽  
Jos van Pelt ◽  
Sofie De Groote ◽  
David Cassiman ◽  
...  
Keyword(s):  
Glutamine Synthetase ◽  
Liver Failure ◽  
Bacterial Infections ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure ◽  
Phenotypic Characterisation ◽  
Severity Scores ◽  
Aclf Patient

ObjectiveAcute-on-chronic liver failure (ACLF) is associated with dysfunctional circulating monocytes whereby patients become highly susceptible to bacterial infections. Here, we identify the pathways underlying monocyte dysfunction in ACLF and we investigate whether metabolic rewiring reinstates their phagocytic and inflammatory capacity.DesignFollowing phenotypic characterisation, we performed RNA sequencing on CD14+CD16− monocytes from patients with ACLF and decompensated alcoholic cirrhosis. Additionally, an in vitro model mimicking ACLF patient-derived features was implemented to investigate the efficacy of metabolic regulators on monocyte function.ResultsMonocytes from patients with ACLF featured elevated frequencies of interleukin (IL)-10-producing cells, reduced human leucocyte antigen DR isotype (HLA-DR) expression and impaired phagocytic and oxidative burst capacity. Transcriptional profiling of isolated CD14+CD16− monocytes in ACLF revealed upregulation of an array of immunosuppressive parameters and compromised antibacterial and antigen presentation machinery. In contrast, monocytes in decompensated cirrhosis showed intact capacity to respond to inflammatory triggers. Culturing healthy monocytes in ACLF plasma mimicked the immunosuppressive characteristics observed in patients, inducing a blunted phagocytic response and metabolic program associated with a tolerant state. Metabolic rewiring of the cells using a pharmacological inhibitor of glutamine synthetase, partially restored the phagocytic and inflammatory capacity of in vitro generated- as well as ACLF patient-derived monocytes. Highlighting its biological relevance, the glutamine synthetase/glutaminase ratio of ACLF patient-derived monocytes positively correlated with disease severity scores.ConclusionIn ACLF, monocytes feature a distinct transcriptional profile, polarised towards an immunotolerant state and altered metabolism. We demonstrated that metabolic rewiring of ACLF monocytes partially revives their function, opening up new options for therapeutic targeting in these patients.

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