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 Use of skeletal muscle index as a predictor of short-term mortality in patients with acute-on-chronic liver failure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tongzeng Li ◽  
Manman Xu ◽  
Ming Kong ◽  
Wenyan Song ◽  
Zhongping Duan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Liver Disease ◽  
Liver Failure ◽  
Chronic Liver Disease ◽  
Serum Bilirubin ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Short Term ◽  
Skeletal Muscle Index ◽  
Short Term Mortality

AbstractSarcopenia is a well-recognized factor affecting the prognosis of chronic liver disease, but its impact on acute decompensation underlying chronic liver disease is unknown. This study evaluated the impact of sarcopenia on short-term mortality in patients with acute-on-chronic liver failure (ACLF). One hundred and seventy-one ACLF patients who underwent abdominal CT between 2015 and 2019 were retrospectively included in this study. Skeletal muscle index at the third lumbar vertebrae (L3-SMI) was used to diagnose sarcopenia.The ACLF patients in this study had a L3-SMI of 41.2 ± 8.3 cm2/m2 and sarcopenia was present in 95/171 (55.6%) patients. Body mass index (BMI), cirrhosis, and higher serum bilirubin were independently associated with sarcopenia. Following multivariate Cox regression analysis, cirrhosis (hazard ratio (HR) 2.758, 95%CI 1.323–5.750), serum bilirubin (HR 1.049, 95%CI 1.026–1.073), and international normalized ratio (INR) (HR 1.725, 95%CI 1.263–2.355) were associated with 3-month mortality (P < 0.05), whereas L3-SMI and sarcopenia were not. A subgroup analysis of the factors related to sarcopenia showed that sarcopenia was still not predictive of short-term outcome in ACLF patients. L3-SMI and sarcopenia are not associated with short-term mortality in patients with ACLF.

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 &lt; 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 &lt; 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.

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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