Global epidemiological burden of fungal infections in cirrhosis patients: A systematic review with meta‐analysis

Abstract

Background and Aims: Fungal infections (FIs) have serious implications, yet understated in cirrhosis. Therefore, we reviewed the epidemiology and trends of FIs among cirrhotics.Methods: Four electronic databases were searched for full-text articles describing prevalence of FIs in cirrhosis. Studies from post-transplant, malignancy and classicalimmuno-deficiency patients were excluded. A random-effects meta-analysis was done to pool estimates of FIs (overall, and by type and infection-site), and their variation(I 2 ) was explored on moderator-analysis and meta-regression. Risk of bias and asymmetry in estimates was assessed by a checklist and Egger's regression, respectively.(CRD42019142782).Results: Thirty-four low-risk and four moderate-risk studies (31 984 cirrhotics) were included. Pooled estimates of overall FIs (17 studies), invasive fungal infections (IFIs; 17 studies), invasive candidiasis (23 studies) and invasive aspergillosis (16 studies) in cirrhosis were 10.2%(6.0-16.9), 9.5%(5.4-16.2), 4.0%(2.0-8.0) and 2.8%(1.5-5.3), respectively (I 2 > 90%;each). Site of FIs in decreasing order of pooled prevalence was pulmonary, urinary tract, bloodstream, peritoneal, oesophageal and cerebral.Geographic differences in these estimates were remarkable, with highest burden of overall FIs from Belgium, the United States and India. Non-albicans-Candida and Aspergillus infections have increased over the last decade in cirrhosis. Intensive-careunit (ICU)-admitted and acute-on-chronic liver failure (ACLF) patients had the highest prevalence of IFIs. MELD score(cases), bias score and sample size across studies were the predictors of variance in overall FI estimates. Diabetes, steroid and broadspectrum antibiotic-exposure, and multiple organ failures were the common predispositions reported in patients with FIs.Conclusions: FIs impose a substantial burden in cirrhosis. ACLF and ICU admission should be considered as a host factor for defining IFIs. Epidemiology of FIs can guide interpretation of biomarkers and antifungal treatment in cirrhosis.

Cirrhosis and fungal infections‐a cocktail for catastrophe: A systematic review and meta‐analysis with machine learning

“…We showed that ACLF and ICU‐admitted patients are the two high‐risk categories among cirrhosis that warrant closer attention. This was in line with our previous reports on the highest‐burden of FIs, 5 the highest risk of death due to IC, 9 and IA, 8 specifically in these two categories of patients. However, studies mediating the mechanisms for such a risk are currently lacking and need further exploration.…”

“…We showed that hospitalised cirrhosis patients, especially those in ICU, are at risk of developing and eventually dying due to FIs. 5,8,9 Such patients are often in ACLF and have alcoholic hepatitis or gastrointestinal bleeds, which severely compromise the gut-liver axis allowing endogenous translocation of altered mycobiome leading to dysregulated immune response and poor outcomes. 62 Our findings indicate that the mortality is higher in patients with pulmonary FIs followed by peritoneal FIs and fungemia.…”

“…1,2 There is an inarguably huge burden and poor outcomes for infections in cirrhosis patients. 3,4 Although bacterial infection is a well-known complication, an increasing prevalence of fungal infections (FIs) 5 and associated morbidity and mortality in cirrhosis patients is alarming. [6][7][8][9] FIs are associated with increased morbidity due to acute kidney injury, hepatic encephalopathy, gastrointestinal bleeding and shock.…”

“…A recent systematic review demonstrated an increasing burden of non-albicans Candida and Aspergillus infections in cirrhosis. 5 Candida and Aspergillus infections were recently shown to have high mortality in cirrhosis. 8,9 However, the cirrhosis sub-population at the highest risk of poor outcomes with FIs is unclear.…”

“…Despite the high risk and poor impact, there is currently a lack of systematic literature evaluating the burden, risk factors and mortality of cirrhosis patients with FIs. A recent systematic review demonstrated an increasing burden of non‐albicans Candida and Aspergillus infections in cirrhosis 5 . Candida and Aspergillus infections were recently shown to have high mortality in cirrhosis 8,9 .…”