Invasive Fungal Infections in Patients of Acute on Chronic Liver Failure

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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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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MELD Score Predicts Fungal Infections in Acute-on-Chronic Liver Failure Patients

The American Journal of Gastroenterology ◽

10.14309/00000434-201710001-00877 ◽

2017 ◽

Vol 112 ◽

pp. S494

Author(s):

Sandeep Yarlagadda ◽

Nehali Patel ◽

Chiu-Hsieh Hsu ◽

Courtney Walker ◽

Sarah Patel ◽

...

Keyword(s):

Liver Failure ◽

Fungal Infections ◽

Meld Score ◽

Chronic Liver ◽

Chronic Liver Failure

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Prognostic Role of Bacterial and Fungal Infections in Patients With Liver Cirrhosis With and Without Acute-on-Chronic Liver Failure: A Prospective 2-Center Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa453 ◽

2020 ◽

Vol 7 (11) ◽

Author(s):

Michele Bartoletti ◽

Maurizio Baldassarre ◽

Marco Domenicali ◽

Russell E Lewis ◽

Maddalena Giannella ◽

...

Keyword(s):

Mortality Rate ◽

Observational Study ◽

Liver Failure ◽

Prospective Observational Study ◽

Fungal Infections ◽

Chronic Liver ◽

Decompensated Cirrhosis ◽

Chronic Liver Failure ◽

Term Survival

Abstract Background Bacterial and fungal infections (BFIs) are frequent in patients with cirrhosis and often trigger acute-on-chronic liver failure (ACLF). This prospective observational study aims to describe the interactions between BFI and ACLF in terms of mortality and related risk factors. Methods We performed a 2-center prospective observational study enrolling hospitalized patients with cirrhosis admitted for acute decompensation. Data were recorded at admission and during hospitalization. Survival was recorded up to 1 year. Results Among the 516 patients enrolled, 108 (21%) were infected at admission, while an additional 61 patients (12%) developed an infection during hospital stay. In the absence of ACLF, the 1-year mortality rate of patients with BFI did not differ from that of patients without BFI (33% vs 31%; P = .553). In contrast, those with ACLF triggered or complicated by BFI had a significantly higher mortality rate than those who remained free from BFI (75% vs 54%; P = .011). Competing risk analysis showed that the negative impact of ACLF-related BFI on long-term prognosis was independent from Model for End-stage Liver Disease (MELD) incorporating serum sodium concentration score, comorbidity, and basal C-reactive protein level. Finally, multivariable logistic regression showed that higher MELD score (P < .001), QuickSOFA score ≥2 points (P = .007), and secondary bloodstream (P = .022) and multidrug-resistant pathogen isolation (P = .030) were independently associated with ACLF in patients with BFI. Conclusions This large prospective study indicated that the adverse impact of BFI on long-term survival in decompensated cirrhosis is not universal but is limited to those patients who also develop ACLF. Both disease severity and microbiological factors predispose infected decompensated patients to ACLF.

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