Invasive fungal infections amongst patients with acute-on-chronic liver failure at high risk for fungal infections

Introduction and aim. Acute-on-chronic liver failure (ACLF) is a syndrome with high short-term mortality, and predicting the prognosis is challenging. This study aimed to compare the performance of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (CysC) in predicting the 90-day mortality in patients with hepatitis B virus (HBV)-associated ACLF (HBV-ACLF). Materials and methods. This prospective, observational study enrolled 54 patients with HBV-ACLF. The serum NGAL and CysC levels were determined. A multivariate logistic regression analysis was used to analyze the independent risk factors of mortality. Results. Serum NGAL, but not CysC, was found to significantly correlate with the total bilirubin, international normalized ratio, and model for end-stage liver disease (MELD). Serum NGAL [odds ratio (OR), 1.008; 95% confidence interval (CI), 1.004–1.012; P < 0.01], but not CysC, was an independent risk factor for developing hepatorenal syndrome. Moreover, NGAL (OR, 1.005; 95% CI, 1.001–1.010; P < 0.01) along with the MELD score was independently associated with the overall survival in patients with HBV-ACLF. Patients with HBV-ACLF were stratified into two groups according to the serum NGAL level at baseline (low risk: <217.11 ng/mL and high risk: ≥217.11 ng/mL). The 90-day mortality rate was 22.73% (5/22) in the low-risk group and 71.88% (23/32) in the high-risk group. Moreover, NGAL, but not CysC, significantly improved the MELD score in predicting the prognosis of HBV-ACLF. Conclusion. The serum NGAL might be superior to CysC in predicting the prognosis of HBV-ACLF with the normal creatinine level.

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Bacterial and fungal infections in acute-on-chronic liver failure: prevalence, characteristics and impact on prognosis

Gut ◽

10.1136/gutjnl-2017-314240 ◽

2017 ◽

Vol 67 (10) ◽

pp. 1870-1880 ◽

Cited By ~ 131

Author(s):

Javier Fernández ◽

Juan Acevedo ◽

Reiner Wiest ◽

Thierry Gustot ◽

Alex Amoros ◽

...

Keyword(s):

Liver Failure ◽

Systemic Inflammation ◽

Bacterial Infections ◽

Clinical Course ◽

Fungal Infections ◽

Chronic Liver ◽

Chronic Liver Failure ◽

Bacterial Peritonitis ◽

Probability Of Survival

Bacterial infection is a frequent trigger of acute-on-chronic liver failure (ACLF), syndrome that could also increase the risk of infection. This investigation evaluated prevalence and characteristics of bacterial and fungal infections causing and complicating ACLF, predictors of follow-up bacterial infections and impact of bacterial infections on survival.Patients407 patients with ACLF and 235 patients with acute decompensation (AD).Results152 patients (37%) presented bacterial infections at ACLF diagnosis; 46%(n=117) of the remaining 255 patients with ACLF developed bacterial infections during follow-up (4 weeks). The corresponding figures in patients with AD were 25% and 18% (p<0.001). Severe infections (spontaneous bacterial peritonitis, pneumonia, severe sepsis/shock, nosocomial infections and infections caused by multiresistant organisms) were more prevalent in patients with ACLF. Patients with ACLF and bacterial infections (either at diagnosis or during follow-up) showed higher grade of systemic inflammation at diagnosis of the syndrome, worse clinical course (ACLF 2-3 at final assessment: 47% vs 26%; p<0.001) and lower 90-day probability of survival (49% vs 72.5%;p<0.001) than patients with ACLF without infection. Bacterial infections were independently associated with mortality in patients with ACLF-1 and ACLF-2. Fungal infections developed in 9 patients with ACLF (2%) and in none with AD, occurred mainly after ACLF diagnosis (78%) and had high 90-day mortality (71%).ConclusionBacterial infections are extremely frequent in ACLF. They are severe and associated with intense systemic inflammation, poor clinical course and high mortality. Patients with ACLF are highly predisposed to develop bacterial infections within a short follow-up period and could benefit from prophylactic strategies.

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Bacterial and fungal infections in acute-on-chronic liver failure: prevalence, characteristics and impact on prognosis

Journal of Hepatology ◽

10.1016/s0168-8278(17)31105-4 ◽

2017 ◽

Vol 66 (1) ◽

pp. S379

Author(s):

J. Fernandez ◽

J. Acevedo ◽

R. Wiest ◽

T. Gustot ◽

A. Amoros ◽

...

Keyword(s):

Liver Failure ◽

Fungal Infections ◽

Chronic Liver ◽

Chronic Liver Failure

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

10.21203/rs.3.rs-1151335/v1 ◽

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.

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

Frontiers in Medicine ◽

10.3389/fmed.2021.752875 ◽

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.

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Assessment of Sepsis-3 criteria and quick SOFA in patients with cirrhosis and bacterial infections

Gut ◽

10.1136/gutjnl-2017-314324 ◽

2017 ◽

Vol 67 (10) ◽

pp. 1892-1899 ◽

Cited By ~ 36

Author(s):

Salvatore Piano ◽

Michele Bartoletti ◽

Marta Tonon ◽

Maurizio Baldassarre ◽

Giada Chies ◽

...

Keyword(s):

Hospital Mortality ◽

Liver Failure ◽

Bacterial Infections ◽

Fungal Infections ◽

Chronic Liver ◽

Population Increase ◽

Chronic Liver Failure ◽

Reactive Protein ◽

Acute Decompensation ◽

Sirs Criteria

IntroductionPatients with cirrhosis have a high risk of sepsis, which confers a poor prognosis. The systemic inflammatory response syndrome (SIRS) criteria have several limitations in cirrhosis. Recently, new criteria for sepsis (Sepsis-3) have been suggested in the general population (increase of Sequential Organ Failure Assessment (SOFA) ≥2 points from baseline). Outside the intensive care unit (ICU), the quick SOFA (qSOFA (at least two among alteration in mental status, systolic blood pressure ≤100 mm Hg or respiratory rate ≥22/min)) was suggested to screen for sepsis. These criteria have never been evaluated in patients with cirrhosis. The aim of the study was to assess the ability of Sepsis-3 criteria in predicting in-hospital mortality in patients with cirrhosis and bacterial/fungal infections.Methods259 consecutive patients with cirrhosis and bacterial/fungal infections were prospectively included. Demographic, laboratory and microbiological data were collected at diagnosis of infection. Baseline SOFA was assessed using preadmission data. Patients were followed up until death, liver transplantation or discharge. Findings were externally validated (197 patients).ResultsSepsis-3 and qSOFA had significantly greater discrimination for in-hospital mortality (area under the receiver operating characteristic (AUROC)=0.784 and 0.732, respectively) than SIRS (AUROC=0.606) (p<0.01 for both). Similar results were observed in the validation cohort. Sepsis-3 (subdistribution HR (sHR)=5.47; p=0.006), qSOFA (sHR=1.99; p=0.020), Chronic Liver Failure Consortium Acute Decompensation score (sHR=1.05; p=0.001) and C reactive protein (sHR=1.01;p=0.034) were found to be independent predictors of in-hospital mortality. Patients with Sepsis-3 had higher incidence of acute-on-chronic liver failure, septic shock and transfer to ICU than those without Sepsis-3.ConclusionsSepsis-3 criteria are more accurate than SIRS criteria in predicting the severity of infections in patients with cirrhosis. qSOFA is a useful bedside tool to assess risk for worse outcomes in these patients. Patients with Sepsis-3 and positive qSOFA deserve more intensive management and strict surveillance.

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