• cirrhosis
• cirrhosis fungal trends
• cirrhosis readmissions
• spontaneous bacterial peritonitis
• spontaneous fungal peritonitis

• Acute-on-chronic liver failure
• Candidemia
• Systemic Fungal infection
• T2 candida panel

• Humans
• Acute-On-Chronic Liver Failure/diagnosis
• Acute-On-Chronic Liver Failure/mortality
• Male
• Female
• Middle Aged
• Retrospective Studies
• Candidiasis, Invasive/drug therapy
• Candidiasis, Invasive/diagnosis
• Antifungal Agents/therapeutic use
• Candida/isolation & purification
• Aged
• Treatment Outcome
• Adult
• Liver Cirrhosis/complications

• Aspergillus
• Candida
• Cryptococcus
• Candidemia
• Candidiasis
• Cryptococcosis
• Fibrosis
• Intensive care units
• Invasive fungal infections
• Invasive pulmonary aspergillosis
• Liver diseases
• Liver failure

• Humans
• Intensive Care Units
• Invasive Fungal Infections/drug therapy
• Liver Diseases/immunology
• Liver Diseases/microbiology
• Liver Diseases/complications
• Antifungal Agents/therapeutic use
• Cryptococcosis/immunology
• Cryptococcosis/complications
• Cryptococcosis/drug therapy

• Acute liver failure
• Bacterial infections
• Fungal infections
• Multi-drug resistance
• Viral infections

• Humans
• Liver Failure, Acute/therapy
• Liver Failure, Acute/diagnosis
• Bacterial Infections/therapy
• Bacterial Infections/prevention & control
• Bacterial Infections/diagnosis
• Bacterial Infections/microbiology
• Mycoses/diagnosis
• Mycoses/therapy
• Mycoses/prevention & control
• Cross Infection/prevention & control
• Cross Infection/diagnosis
• Cross Infection/therapy

• (1, 3)-β-d-glucan
• Biomarker
• Downslope
• Invasive candidiasis

• Humans
• Middle Aged
• Male
• Candidiasis, Invasive/blood
• Candidiasis, Invasive/mortality
• Candidiasis, Invasive/diagnosis
• Female
• Intensive Care Units/statistics & numerical data
• Intensive Care Units/organization & administration
• beta-Glucans/blood
• beta-Glucans/analysis
• Prognosis
• Adult
• Cohort Studies
• Italy/epidemiology
• Biomarkers/blood
• Biomarkers/analysis
• Proteoglycans/blood
• Proteoglycans/analysis
• Predictive Value of Tests

• In-hospital mortality
• Liver cirrhosis
• Nomogram
• Prognosis
• Sepsis

• Humans
• Liver Cirrhosis/mortality
• Liver Cirrhosis/complications
• Nomograms
• Hospital Mortality
• Sepsis/mortality
• Male
• Female
• Middle Aged
• Retrospective Studies
• Aged
• Risk Factors
• Prognosis
• ROC Curve
• Adult
• Area Under Curve

• ACHBLF: acute-on-chronic hepatitis B liver failure
• ACLF: acute-on-chronic liver failure
• HBV: hepatitis B virus
• IFI: invasive fungal infection
• risk factors

• Humans
• Liver Diseases/epidemiology
• Invasive Fungal Infections/diagnosis
• Invasive Fungal Infections/epidemiology
• Liver Transplantation
• Hepatitis, Alcoholic
• Cytodiagnosis

• R01 AI132638 NIAID NIH HHS

• CYP2C19
• dose adjustment
• genetic polymorphism
• hepatic insufficiency
• invasive fungal infections
• voriconazole

• Candida
• candidemia
• candidiasis
• fungal community
• fungal microbiota
• invasive candidiasis
• mycoses
• yeast infections
• yeasts

• SZPITALE-JEDNOIMIENNE/18/2020 National Centre for Research and Development

• ascites
• fungiascites
• nomogram
• spontaneous bacterial peritonitis
• spontaneous fungal peritonitis

• 2022-1-2181 Capital Medical Development and Research Fund
• BJYAYY-YN2022-07 Young and Middle-aged Talent Incubation Programme of Beijing You'an Hospital

• Cirrhosis
• Intensive care unit
• Mycology
• Peritonitis

The landscape of invasive candidiasis and invasive aspergillosis has changed dramatically in intensive care units over the past two decades. Today, we are faced with new risk factors such as the emergence of resistance, but are also equipped with new therapeutic strategies and diagnostic tools which are changing epidemiological data and diagnostic algorithms. Some common points need to be addressed: (i) the best way to use microbiological tools and to integrate their results in decisional algorithms; (ii) the need to find the optimum balance between under-diagnosis and overtreatment; (iii) and the need to decipher pathophysiology. In this short review, we will try to illustrate these points.

• ACLF
• antifungals
• cirrhosis
• invasive fungal infections
• machine learning
• mortality

• Bacteremia/complications
• Bacteremia/epidemiology
• Bacteremia/microbiology
• Candidemia/drug therapy
• Candidemia/epidemiology
• Candidemia/microbiology
• Cross Infection/epidemiology
• End Stage Liver Disease/complications
• Humans
• Intensive Care Units
• Liver Cirrhosis/complications
• Retrospective Studies
• Risk Factors
• Severity of Illness Index

• Candida
• Intra-abdominal infection
• Invasive candidiasis
• Risk factors

• Candida glabrata
• antifungal resistance
• azoles
• echinocandines
• ibero-america

• candidemia
• end-stage liver disease
• invasive fungal infection
• invasive pulmonary aspergillosis
• liver impairment
• severe alcoholic steatohepatitis

• Candida
• Cirrhosis
• Invasive candidiasis
• fungal infection
• meta-analysis
• mortality
• systematic review

• Acute-On-Chronic Liver Failure/microbiology
• Acute-On-Chronic Liver Failure/mortality
• Candidiasis, Invasive/pathology
• End Stage Liver Disease/microbiology
• End Stage Liver Disease/mortality
• Humans
• Intensive Care Units
• Liver Cirrhosis/microbiology
• Liver Cirrhosis/mortality
• Severity of Illness Index

Critically ill cirrhotic patients have high in-hospital mortality and utilize significant health care resources as a consequence of the need for multiorgan support. Despite this fact, their mortality has decreased in recent decades due to improved care of critically ill patients. Acute-on-chronic liver failure (ACLF), sepsis and elevated hepatic scores are associated with increased mortality in this population, especially among those not eligible for liver transplantation. No score is superior to another in the prognostic assessment of these patients, and both liver-specific and intensive care unit-specific scores have satisfactory predictive accuracy. The sequential assessment of the scores, especially the Sequential Organ Failure Assessment (SOFA) and Chronic Liver Failure Consortium (CLIF)-SOFA scores, may be useful as an auxiliary tool in the decision-making process regarding the benefits of maintaining supportive therapies in this population. A CLIF-ACLF > 70 at admission or at day 3 was associated with a poor prognosis, as well as SOFA score > 19 at baseline or increasing SOFA score > 72. Additional studies addressing the prognostic assessment of these patients are necessary.

• Cirrhosis
• Extrahepatic organ failure
• Organ replacement therapy
• Mortality
• Prognostic scores
• Chronic Liver Failure Consortium-Sequential Organ Failure Assessment
• Sequential Organ Failure Assessment
• Model for End-stage Liver Disease

This prospective observational study aimed to clinically describe voriconazole administrations and trough concentrations in patients with Child–Pugh class C and to investigate the variability of trough concentration. A total of 144 voriconazole trough concentrations from 43 Child–Pugh class C patients were analyzed. The majority of patients (62.8%) received adjustments. The repeated measured trough concentration was higher than the first and final ones generally (median, 4.33 vs. 2.99, 3.90 mg/L). Eight patients with ideal initial concentrations later got supratherapeutic with no adjusted daily dose, implying accumulation. There was a significant difference in concentrations among the six groups by daily dose (p = 0.006). The bivariate correlation analysis showed that sex, CYP2C19 genotyping, daily dose, prothrombin time activity, international normalized ratio, platelet, and Model for end-stage liver disease score were significant factors for concentration. Subsequently, the first four factors mentioned above entered into a stepwise multiple linear regression model (variance inflation factor <5), implying that CYP2C19 testing makes sense for precision medicine of Child–Pugh class C cirrhosis patients. The equation fits well and explains the 34.8% variety of concentrations (R² = 0.348). In conclusion, it needs more cautious administration clinically due to no recommendation for Child–Pugh class C patients in the medication label. The adjustment of the administration regimen should be mainly based on the results of repeated therapeutic drug monitoring.

• CYP2C19
• Child–Pugh C cirrhosis
• administration
• trough concentrations
• voriconazole

• MUST
• non-albicans candidemia
• nutritional assessment

• Aged
• Aged, 80 and over
• Antifungal Agents/therapeutic use
• Candida/classification
• Candida/drug effects
• Candidemia/mortality
• Female
• Humans
• Male
• Malnutrition/pathology
• Middle Aged
• Nutrition Assessment
• Nutritional Status
• Retrospective Studies

• abstinence
• alcohol-associated liver disease
• fungi
• microbiome
• mycobiome

• R01 AA020703 NIAAA NIH HHS
• I01 BX004594 BLRD VA
• P30 DK120515 NIDDK NIH HHS
• R01 AA024726 NIAAA NIH HHS
• P50 AA011999 NIAAA NIH HHS
• U01 AA026939 NIAAA NIH HHS

• antimicrobial therapy
• intraabdominal infection
• nutrition
• source control
• treatment failure

Candida tropicalis (C. tropicalis) is an important opportunistic pathogenic Candida species that can cause nosocomial infection. In this study, we analyzed the distribution and drug susceptibility of C. tropicalis and the relationship between ERG11 and UPC2 expression and resistance to azole antifungal agents.

C. tropicalis was cultured and identified by Sabouraud Agar Medium, CHROM Agar Candida and ATB tests (Bio-Mérieux, France). Total RNA was extracted from the collected strains, and the ERG11 and UPC2 mRNA expression levels were analyzed by quantitative real-time PCR.

In total, 2872 clinical isolates of Candida, including 319 strains of C. tropicalis, were analyzed herein; they were mainly obtained from the Departments of Respiratory Medicine and ICU. The strains were predominantly isolated from airway secretion samples, and the detection trend in four years was mainly related to the type of department and specimens. The resistance rates of C. tropicalis to fluconazole, itraconazole and voriconazole had been increasing year by year. The mRNA expression levels of ERG11 and UPC2 in the fluconazole-resistant group were significantly higher than they were in the susceptible group. In addition, there was a significant positive linear correlation between these two genes in the fluconazole-resistant group.

Overexpression of the ERG11 and UPC2 genes in C. tropicalis could increase resistance to azole antifungal drugs. The routine testing for ERG11 and UPC2 in high-risk patients in key departments would provide a theoretical basis for the rational application of azole antifungal drugs.

• Candida tropicalis
• Drug resistance
• ERG11
• UPC2

Invasive infections are a major complication before liver transplantation (LT) and in the early phase after surgery. There has been an increasing prevalence of invasive fungal disease (IFD), especially among the sickest patients with decompensated cirrhosis and acute-on-chronic liver failure, who suffer from a profound state of immune dysfunction and receive intensive care management. In such patients, who are listed for LT, development of an IFD often worsens hepatic and extra-hepatic organ dysfunction, requiring a careful evaluation before surgery. In the post-transplant setting, the burden of IFD has been reduced after the clinical advent of antifungal prophylaxis, even if several major issues still remain, such as duration, target population and drug type(s). Nevertheless, the development of IFD in the early phase after surgery significantly impairs graft and patient survival. This review outlines presentation, prophylactic and therapeutic strategies, and outcomes of IFD in LT candidates and recipients, providing specific considerations for clinical practice.

• Acute-on-chronic liver failure
• Sepsis
• Cirrhosis
• Candidemia
• Acute liver failure
• Invasive fungal infection

• Antifungal Agents/therapeutic use
• Humans
• Invasive Fungal Infections/diagnosis
• Invasive Fungal Infections/drug therapy
• Invasive Fungal Infections/epidemiology
• Liver Transplantation/adverse effects
• Mycoses/diagnosis
• Mycoses/drug therapy
• Mycoses/epidemiology

• Cancer
• Candidemia
• Meyerozyma guilliermondii complex
• Mortality
• Risk factor

• Bacterial infection
• Cirrhosis
• Fungal infections
• Multidrug resistant bacteria

• Acute-on-chronic liver failure
• Bloodstream infection
• Candidaemia
• Liver cirrhosis
• Rifaximin

• Candidemia
• Intra-abdominal candidiasis
• Risk factors
• Septic shock

• Liver cirrhosis
• bacterial infections
• fungal infections
• multidrug-resistant pathogens
• novel beta-lactams

Spontaneous peritonitis is one of the most common infectious complications in cirrhotic patients with ascites. Spontaneous fungal peritonitis (SFP) is a type of spontaneous peritonitis that is a less recognized but devastating complication in end-stage cirrhosis. Although high mortality was previously noted, scant data are available to fully define the factors responsible for the occurrence of SFP and its mortality.

To illustrate the differences between SFP and spontaneous bacterial peritonitis (SBP) and discuss the risk factors for the occurrence of SFP and its short-term mortality.

We performed a matched case-control study between January 1, 2007 and December 30, 2018. Patients with SFP were included in a case group. Sex-, age-, and time-matched patients with SBP were included in a control group and were further divided into control-1 group (positive bacterial culture) and control-2 group (negative bacterial culture). The clinical features and laboratory parameters, severity models, and prognosis were compared between the case and control groups. Logistic regression analysis was used to determine the risk factors for occurrence, and the Cox regression model was used to identify the predictive factors for short-term mortality of SFP.

Patients with SFP exhibited more severe systemic inflammation, higher ascites albumin and polymorphonuclear neutrophils, and a worsened 15-d mortality than patients in the control groups. Antibiotic administration (case vs control-1: OR = 1.063, 95%CI: 1.012-1.115, P = 0.014; case vs control-2: OR = 1.054, 95%CI: 1.014-1.095, P = 0.008) remarkably increased the occurrence of SFP or fungiascites. Hepatorenal syndrome (HR = 5.328, 95%CI: 1.050-18.900) and total bilirubin (μmol/L; HR = 1.005, 95%CI: 1.002-1.008) represented independent predictors of SFP-related early mortality.

Long-term antibiotic administration increases the incidence of SFP, and hepatorenal syndrome and total bilirubin are closely related to short-term mortality.

• Spontaneous fungal peritonitis
• Risk factor
• Cirrhosis

Spontaneous peritonitis is an infection of ascitic fluid without a known intra-abdominal source of infection. spontaneous fungal peritonitis (SFP) is a potentially fatal complication of decompensated cirrhosis, defined as fungal infection of ascitic fluid in the presence of ascitic neutrophil count of greater than 250 cells/mL.

To determine the prevalence of fungal pathogens, management and outcomes (mortality) of SFP in critically ill cirrhotic patients.

Studies were identified using PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Scopus databases until February 2019. Inclusion criteria included intervention trials and observation studies describing the association between SFP and cirrhosis. The primary outcome was in-hospital, 1-mo, and 6-mo mortality rates of SFP in cirrhotic patients. Secondary outcomes were fungal microorganisms identified and in hospital management by anti-fungal medications. The National Heart, Lung and Blood Institute quality assessment tools were used to assess internal validity and risk of bias for each included study.

Six observational studies were included in this systematic review. The overall quality of included studies was good. A meta-analysis of results could not be performed because of differences in reporting of outcomes and heterogeneity of the included studies. There were 82 patients with SFP described across all the included studies. Candida species, predominantly Candida albicans was the fungal pathogen in majority of the cases (48%-81.8%) followed by Candida krusei (15%-25%) and Candida glabrata (6.66%-20%). Cryptococcus neoformans (53.3%) was the other major fungal pathogen. Antifungal therapy in SFP patients was utilized in 33.3% to 81.8% cases. The prevalence of in hospital mortality ranged from 33.3% to 100%, whereas 1-mo mortality ranged between 50% to 73.3%.

This systematic review suggests that SFP in end stage liver disease patient is associated with high mortality both in the hospital and at 1-mo, and that antifungal therapy is currently underutilized.

• Spontaneous fungal peritonitis
• Bacterial peritonitis
• Liver
• Cirrhosis
• Critical

The objective of this study was to assess the cumulative incidence of invasive candidiasis (IC) in intensive care units (ICUs) in Europe.

A multinational, multicenter, retrospective study was conducted in 23 ICUs in 9 European countries, representing the first phase of the candidemia/intra-abdominal candidiasis in European ICU project (EUCANDICU).

During the study period, 570 episodes of ICU-acquired IC were observed, with a cumulative incidence of 7.07 episodes per 1000 ICU admissions, with important between-center variability. Separated, non-mutually exclusive cumulative incidences of candidemia and IAC were 5.52 and 1.84 episodes per 1000 ICU admissions, respectively. Crude 30-day mortality was 42%. Age (odds ratio [OR] 1.04 per year, 95% CI 1.02–1.06, p < 0.001), severe hepatic failure (OR 3.25, 95% 1.31–8.08, p 0.011), SOFA score at the onset of IC (OR 1.11 per point, 95% CI 1.04–1.17, p 0.001), and septic shock (OR 2.12, 95% CI 1.24–3.63, p 0.006) were associated with increased 30-day mortality in a secondary, exploratory analysis.

The cumulative incidence of IC in 23 European ICUs was 7.07 episodes per 1000 ICU admissions. Future in-depth analyses will allow explaining part of the observed between-center variability, with the ultimate aim of helping to improve local infection control and antifungal stewardship projects and interventions.

• Abdominal candidiasis
• Candida
• Candidemia
• Candidiasis
• ICU
• Incidence